IDM : NeuroScience References / Further Reading

1Department of Radiology2Department of Neurology and3Department of Psychiatry4Center for Functional Neuroimaging, University of Pennsylvania, Philadelphia, PA5Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA

Gender is an important biological determinant of vulnerability to psychosocial stress. We used perfusion based functional magnetic resonance imaging (fMRI) to measure cerebral blood flow (CBF) responses to mild to moderate stress in 32 healthy people (16 males and 16 females). Psychological stress was elicited using mental arithmetic tasks under varying pressure. Stress in men was associated with CBF increase in the right prefrontal cortex (RPFC) and CBF reduction in the left orbitofrontal cortex (LOrF), a robust response that persisted beyond the stress task period. In contrast, stress in women primarily activated the limbic system, including the ventral striatum, putamen, insula and cingulate cortex. The asymmetric prefrontal activity in males was associated with a physiological index of stress responses—salivary cortisol, whereas the female limbic activation showed a lower degree of correlations with cortisol. Conjunction analyses indicated only a small degree of overlap between the stress networks in men and women at the threshold level of P < 0.01. Increased overlap of stress networks between the two genders was revealed when the threshold for conjunction analyses was relaxed to P < 0.05. Further, machine classification was used to differentiate the central stress responses between the two genders with over 94% accuracy. Our study may represent an initial step in uncovering the neurobiological basis underlying the contrasting health consequences of psychosocial stress in men and women.

Keywords: cerebral blood flow (CBF); arterial spin labeling (ASL); right prefrontal cortex (RPFC); left orbitofrontal cortex (LOrF); anterior cingulate cortex (ACC)

Research Articles

Prefrontal Regions Orchestrate Suppression of Emotional Memories via a Two-Phase Process

Brendan E. Depue,1,2* Tim Curran,1,2,3 Marie T. Banich1,2,3,4

Whether memories can be suppressed has been a controversial issue in psychology and cognitive neuroscience for decades. We found evidence that emotional memories are suppressed via two time-differentiated neural mechanisms: (i) an initial suppression by the right inferior frontal gyrus over regions supporting sensory components of the memory representation (visual cortex, thalamus), followed by (ii) right medial frontal gyrus control over regions supporting multimodal and emotional components of the memory representation (hippocampus, amygdala), both of which are influenced by fronto-polar regions. These results indicate that memory suppression does occur and, at least in nonpsychiatric populations, is under the control of prefrontal regions.

1 Department of Psychology, University of Colorado, Boulder, CO 80309, USA.
2 Center for Neuroscience, University of Colorado, Boulder, CO 80309, USA.
3 Institute of Cognitive Science, University of Colorado, Boulder, CO 80309, USA.
4 Department of Psychiatry, University of Denver Health Sciences, Denver, CO 80208, USA.

Visual Cognition
Issue: Volume 12, Number 5 / July 2005
Pages: 720 - 736
URL: Linking Options
Unconscious and conscious priming by forms and their parts

Bruno G. Breitmeyer , Haluk Ogmen , Jose Ramon , Jian Chen

A1 University of Houston, TX, USA

Abstract:

Using metacontrast masking techniques, in two experiments we compare unconscious and conscious response priming by targets consisting of either whole forms or else their parts. In Experiment 1 we investigate the contribution of whole forms and their figural primitives, viz., edges and corners, to the unconscious priming effect. As expected, choice RTs were fast when the invisible target and visible mask shape pairings were congruent and slower when they were incongruent. This trend, while strongest for whole-targets, also held for the target primes composed only of corners but did not hold for target primes composed only of sides. Experiment 2 showed, replicating the results of Experiment 1, that while invisible corner targets produced weaker priming effects than invisible whole targets, paradoxically visible corner target produced stronger priming effects than visible whole targets. Taken together the results of the two experiments indicate (a) that unconscious target representations and, thus, unconscious priming effects are strongest when the target is a complete rather than a partial configuration, (b) that conjunctions of line or edge orientations forming corners produce stronger unconscious target representations and priming effects than do unconscious target representations formed from nonconjoined edge or line primitives, (c) that metacontrast masking of form occurs at or beyond levels of visual processing at which feature integration of visual form primitives occurs, and (d) that, when consciously perceived, partial forms can act as stronger primes than whole forms.

Multisensory spatial interactions: a window onto functional integration in the human brain

Emiliano Macalusoa, and Jon Driverb

aNeuroimaging Laboratory, Fondazione Santa Lucia, IRCCS, Via Ardeatina, 306-00179 Rome, Italy
bInstitute of Cognitive Neuroscience and Department of Psychology, University College London, 17 Queen Square, London WC1N 3AR, UK

Available online 1 April 2005.

Incoming signals from different sensory modalities are initially processed in separate brain regions. But because these different signals can arise from common events or objects in the external world, integration between them can be useful. Such integration is subject to spatial and temporal constraints, presumably because a common source is more likely for information arising from around the same place and time. This review focuses on recent neuroimaging data concerning spatial aspects of multisensory integration in the human brain. These findings indicate not only that multisensory integration involves anatomical convergence from sensory-specific (‘unimodal’) cortices into multisensory (‘heteromodal’) brain areas, but also that multisensory spatial interactions can affect even so-called ‘unimodal’ brain regions. Such findings call for a revision of traditional assumptions about multisensory processing in the brain.

Trends in Neurosciences
Volume 28, Issue 5 , May 2005, Pages 264-271

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Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17288-93. Epub 2004 Dec 7.

Neural synchrony indexes disordered perception and cognition in schizophrenia.

Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, Frumin M, Shenton ME, McCarley RW.

Department of Psychiatry, Veterans Affairs Boston Healthcare System, Harvard Medical School, Psychiatry 116A, 940 Belmont Street, Brockton, MA 02301, USA.

Current views of schizophrenia suggest that it results from abnormalities in neural circuitry, but empirical evidence in the millisecond range of neural activity has been difficult to obtain. In pursuit of relevant evidence, we previously demonstrated that schizophrenia is associated with abnormal patterns of stimulus-evoked phaselocking of the electroencephalogram in the gamma band (30-100 Hz). These patterns may reflect impairments in neural assemblies, which have been proposed to use gamma-band oscillations as a mechanism for synchronization. Here, we report the unique finding that, in both healthy controls and schizophrenia patients, visual Gestalt stimuli elicit a gamma-band oscillation that is phase-locked to reaction time and hence may reflect processes leading to conscious perception of the stimuli. However, the frequency of this oscillation is lower in schizophrenics than in healthy individuals. This finding suggests that, although synchronization must occur for perception of the Gestalt, it occurs at a lower frequency because of a reduced capability of neural networks to support high-frequency synchronization in the brain of schizophrenics. Furthermore, the degree of phase locking of this oscillation is correlated with visual hallucinations, thought disorder, and disorganization in the schizophrenia patients. These data provide support for linking dysfunctional neural circuitry and the core symptoms of schizophrenia.

IDM COMMENT: NOTE ASSOCIATION TO SYNCHRONISATIONS - INDICATES SOMA AND SO MEDIATION "ISSUES" WHERE THE CHOICES OF REPRESENTATION ARE TOO MUCH OR "OUT OF BOUNDS".

Nat Rev Neurosci. 2001 Oct;2(10):704-16.

Dynamic predictions: oscillations and synchrony in top-down processing.

Engel AK, Fries P, Singer W.

Cellular Neurobiology Group, Institute for Medicine, Research Centre Julich, 52425 Julich, Germany. a.k.engel@fz-juelich.de

Classical theories of sensory processing view the brain as a passive, stimulus-driven device. By contrast, more recent approaches emphasize the constructive nature of perception, viewing it as an active and highly selective process. Indeed, there is ample evidence that the processing of stimuli is controlled by top-down influences that strongly shape the intrinsic dynamics of thalamocortical networks and constantly create predictions about forthcoming sensory events. We discuss recent experiments indicating that such predictions might be embodied in the temporal structure of both stimulus-evoked and ongoing activity, and that synchronous oscillations are particularly important in this process. Coherence among subthreshold membrane potential fluctuations could be exploited to express selective functional relationships during states of expectancy or attention, and these dynamic patterns could allow the grouping and selection of distributed neuronal responses for further processing.

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Neuron. 2004 Apr 22;42(2):335-46.

A Touching Sight; SII/PV Activation during the Observation and Experience of Touch.

Keysers C, Wicker B, Gazzola V, Anton JL, Fogassi L, Gallese V.

BCN Neuroimaging Centre, University of Groningen, 9713 AW Groningen, The Netherlands.

Watching the movie scene in which a tarantula crawls on James Bond's chest can make us literally shiver-as if the spider crawled on our own chest. What neural mechanisms are responsible for this "tactile empathy"? The observation of the actions of others activates the premotor cortex normally involved in the execution of the same actions. If a similar mechanism applies to the sight of touch, movies depicting touch should automatically activate the somatosensory cortex of the observer. Here we found using fMRI that the secondary but not the primary somatosensory cortex is activated both when the participants were touched and when they observed someone or something else getting touched by objects. The neural mechanisms enabling our own sensation of touch may therefore be a window also to our understanding of touch.

Neuron. 2003 Oct 30;40(3):655-64.

Both of us disgusted in My insula: the common neural basis of seeing and feeling disgust.

Wicker B, Keysers C, Plailly J, Royet JP, Gallese V, Rizzolatti G.

Institut de Neurosciences Physiologiques et Cognitives, CNRS, Chemin Joseph Aiguier, 13402 cedex 20, Marseille, France.

What neural mechanism underlies the capacity to understand the emotions of others? Does this mechanism involve brain areas normally involved in experiencing the same emotion? We performed an fMRI study in which participants inhaled odorants producing a strong feeling of disgust. The same participants observed video clips showing the emotional facial expression of disgust. Observing such faces and feeling disgust activated the same sites in the anterior insula and to a lesser extent in the anterior cingulate cortex. Thus, as observing hand actions activates the observer's motor representation of that action, observing an emotion activates the neural representation of that emotion. This finding provides a unifying mechanism for understanding the behaviors of others.

J Theor Biol. 2003 Feb 7;220(3):345-57.

Reputation and the evolution of conflict.

McElreath R.

Department of Anthropology, University of California, Davis, One Shields Avenue, Davis, CA 95616-8522, USA. mcelreath@davis.edu

The outcomes of conflicts in many human societies generate reputation effects that influence the nature of later conflicts. Those willing to escalate over even trivial offenses are considered honorable whereas those who do not are considered dishonorable (Nisbett & Cohen, 1996). Here I extend Maynard Smith's hawk-dove model of animal conflict to explore the logic of a strategy which uses reputation about its opponents to regulate its behavior. I show that a reputation-based strategy does well when (1) the value of the resource is large relative to the cost of losing a fight, (2) communities are stable, and (3) reputations are well known but subject to some amount of error. Reputation-based strategies may thus result in greater willingness to fight, but less fighting at equilibrium, depending upon the nature of the contests and the local socioecology. Additionally, this strategy is robust in the presence of poor knowledge about reputation.

J Pers Soc Psychol. 2003 Aug;85(2):363-72.

Conversing across cultures: East-West communication styles in work and nonwork contexts.

Sanchez-Burks J, Lee F, Choi I, Nisbett R, Zhao S, Koo J.

Business School and Institute of Social Research, University of Michigan, Ann Arbor 48109, USA. jeffrysb@umich.edu

Four experiments provided evidence that East-West differences in attention to indirect meaning are more pronounced in work settings compared with nonwork settings as suggested by prior research on Protestant relational ideology. Study 1 compared errors in interpreting indirect messages in work and nonwork contexts across three cultures. Studies 2 and 3 examined differences in self-reported indirectness with coworkers versus nonwork acquaintances across three cultures controlling for variation in individualism--collectivism. Study 4 examined self-reported indirectness in bicultural managers and experimentally manipulated the salience of Western versus Eastern culture. The results showed that Americans, but not East Asians, were less attentive to indirect cues in work than nonwork settings and that East-West differences in indirectness were greater in work than nonwork settings.

: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11163-70. Epub 2003 Sep 05.

Culture and point of view.

Nisbett RE, Masuda T.

Department of Psychology, University of Michigan, Ann Arbor, MI 48109, USA. nisbett@umich.edu

East Asians and Westerners perceive the world and think about it in very different ways. Westerners are inclined to attend to some focal object, analyzing its attributes and categorizing it in an effort to find out what rules govern its behavior. Rules used include formal logic. Causal attributions tend to focus exclusively on the object and are therefore often mistaken. East Asians are more likely to attend to a broad perceptual and conceptual field, noticing relationships and changes and grouping objects based on family resemblance rather than category membership. Causal attributions emphasize the context. Social factors are likely to be important in directing attention. East Asians live in complex social networks with prescribed role relations. Attention to context is important to effective functioning. More independent Westerners live in less constraining social worlds and have the luxury of attending to the object and their goals with respect to it. The physical "affordances" of the environment may also influence perception. The built environments of the East are more complex and contain more objects than do those of the West. In addition, artistic products of the East emphasize the field and deemphasize individual objects, including people. Western art renders less of the field and emphasizes individual objects and people.

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NeuroImage
Volume 20, Issue 4 , December 2003, Pages 2181-2196

Copyright © 2003 Elsevier Inc. All rights reserved.

Multilingualism: an fMRI study

Guy Vingerhoetsa, John Van Borsel, , b, Cathelijne Tesinka, Maurits van den Noorta, Karel Deblaerec, Ruth Seurincka, Pieter Vandemaelec and Eric Achtenc

a Laboratory for Neuropsychology, Ghent University, Ghent, Belgium
b ENT-Department, Ghent University Hospital, Ghent, Belgium
c Department of Radiology, Ghent University, Ghent, Belgium

Received 17 December 2002; revised 3 July 2003; accepted 11 July 2003. ; Available online 14 November 2003.

Abstract
To investigate the hypothesis that in multilingual speakers different languages are represented in distinct brain regions, 12 multilingual right-handed men performed a word fluency task, a picture naming task, a comprehension reading task, and their respective control tasks in three languages (Dutch, French, and English) while whole-head functional magnetic resonance imaging (fMRI) was applied. In general, all language tasks revealed predominantly overlapping regions of activation for the different languages. Cerebral activation during use of the foreign languages showed a tendency toward a more extensive recruitment of the areas activated in the native language and the activation of a greater number of regions. Word generation in the foreign languages elicited additional bilateral inferior frontal activation, including Broca's area and left middle temporal gyrus activation; in the native language, additional postcentral activation was found. Picture naming in the foreign languages recruited additional inferior-lateral and medial frontal regions predominantly on the left, and more posterior right hemispheric activation in the mother tongue. During comprehension reading there was more activation in medial posterior regions in the native language. Our results suggest that the performance of language tasks in different languages engages largely the same cerebral areas but that the brain, to perform at a comparable proficiency level, engages more neural substrates for later acquired languages. Our findings do not support the view that languages learned later in life entail more right hemispheric involvement. Finally, a consequent effect of language exposure was found for reading, where increased familiarity engages more occipital activation whereas decreased familiarity appears to be associated with increased left hemispheric inferior frontal activation.

NeuroImage
Volume 20, Issue 4 , December 2003, Pages 2119-2125

Copyright © 2003 Elsevier Inc. All rights reserved.
Regular article

One brain, two selves

A. A. T. S. Reinders, , a, E. R. S. Nijenhuisb, A. M. J. Paansc, J. Korfa, A. T. M. Willemsenc and J. A. den Boera

a Department of Biological Psychiatry, Groningen University Hospital, The Netherlands
b Mental Health Care (Assen)/Cats-Polm Institute (Zeist), The Netherlands
c PET-center, Groningen University Hospital, The Netherlands

Received 12 May 2003; revised 6 July 2003; accepted 18 August 2003. ; Available online 14 November 2003.

Abstract
Having a sense of self is an explicit and high-level functional specialization of the human brain. The anatomical localization of self-awareness and the brain mechanisms involved in consciousness were investigated by functional neuroimaging different emotional mental states of core consciousness in patients with Multiple Personality Disorder (i.e., Dissociative Identity Disorder (DID)). We demonstrate specific changes in localized brain activity consistent with their ability to generate at least two distinct mental states of self-awareness, each with its own access to autobiographical trauma-related memory. Our findings reveal the existence of different regional cerebral blood flow patterns for different senses of self. We present evidence for the medial prefrontal cortex (MPFC) and the posterior associative cortices to have an integral role in conscious experience.

In two minds: dual-process accounts of reasoning
Jonathan St. B.T. Evans
Centre for Thinking and Language, University of Plymouth, Plymouth, PL4 8AA, UK

Researchers in thinking and reasoning have proposed
recently that there are two distinct cognitive systems
underlying reasoning. System 1 is old in evolutionary
terms and shared with other animals: it comprises a set
of autonomous subsystems that include both innate
input modules and domain-specific knowledge acquired
by a domain-general learning mechanism. System 2 is
evolutionarily recent and distinctively human: it permits
abstract reasoning and hypothetical thinking, but is
constrained by working memory capacity and corre-lated
with measures of general intelligence. These
theories essentially posit two minds in one brain with a
range of experimental psychological evidence showing
that the two systems compete for control of our infer-ences
and actions.

Psychosom Med. 2003 Jul-Aug;65(4):564-70.

Alterations in brain and immune function produced by mindfulness meditation.

Davidson RJ, Kabat-Zinn J, Schumacher J, Rosenkranz M, Muller D, Santorelli SF, Urbanowski F, Harrington A, Bonus K, Sheridan JF.

Laboratory for Affective Neuroscience (R.J.D., J.S., M.R.), Department of Psychology, University of Wisconsin, Madison, Wisconsin.

OBJECTIVE: The underlying changes in biological processes that are associated with reported changes in mental and physical health in response to meditation have not been systematically explored. We performed a randomized, controlled study on the effects on brain and immune function of a well-known and widely used 8-week clinical training program in mindfulness meditation applied in a work environment with healthy employees. METHODS: We measured brain electrical activity before and immediately after, and then 4 months after an 8-week training program in mindfulness meditation. Twenty-five subjects were tested in the meditation group. A wait-list control group (N = 16) was tested at the same points in time as the meditators. At the end of the 8-week period, subjects in both groups were vaccinated with influenza vaccine. RESULTS: We report for the first time significant increases in left-sided anterior activation, a pattern previously associated with positive affect, in the meditators compared with the nonmeditators. We also found significant increases in antibody titers to influenza vaccine among subjects in the meditation compared with those in the wait-list control group. Finally, the magnitude of increase in left-sided activation predicted the magnitude of antibody titer rise to the vaccine. CONCLUSIONS: These findings demonstrate that a short program in mindfulness meditation produces demonstrable effects on brain and immune function. These findings suggest that meditation may change brain and immune function in positive ways and underscore the need for additional research.

J Abnorm Psychol. 2002 Nov;111(4):676-81.

Frontal brain asymmetry in restrained eaters.

Silva JR, Pizzagalli DA, Larson CL, Jackson DC, Davidson RJ.

Psychobiology Department, Complutense University, Madrid, Spain.

It is well known that the eating patterns that restrain chronic dieters (restrained eaters) can be disinhibited by anxiety, which in turn has been associated with relative right frontal brain activity in independent electroencephalographic (EEG) studies. Combining these two lines of evidence, the authors tested the hypothesis that chronic restrained eating is associated with relative right frontal asymmetry. Resting anterior brain asymmetry and self-reported measures of anxiety and depression were collected in 23 restrained and 32 unrestrained eaters. As hypothesized, groups differed in tonic frontal activity, with restrained eaters showing more relative right frontal activity. Furthermore, relative right frontal activity was associated with greater self-reported restraint. Right-sided prefrontal asymmetry may thus represent a diathesis associated with increased vulnerability toward restrained eating.

Arch Gen Psychiatry. 2003 Aug;60(8):789-96.

Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety.

Kendler KS, Hettema JM, Butera F, Gardner CO, Prescott CA.

Virginia Institute for Psychiatry and Behavioral Genetics, Medical College of Virginia of Virginia Commonwealth University, Richmond, USA.

BACKGROUND: Although substantial evidence suggests that stressful life events predispose to the onset of episodes of depression and anxiety, the essential features of these events that are depressogenic and anxiogenic remain uncertain. METHODS: High contextual threat stressful life events, assessed in 98 592 person-months from 7322 male and female adult twins ascertained from a population-based registry, were blindly rated on the dimensions of humiliation, entrapment, loss, and danger and their categories. Onsets of pure major depression (MD), pure generalized anxiety syndrome (GAS) (defined as generalized anxiety disorder with a 2-week minimum duration), and mixed MD-GAS episodes were examined using logistic regression. RESULTS: Onsets of pure MD and mixed MD-GAS were predicted by higher ratings of loss and humiliation. Onsets of pure GAS were predicted by higher ratings of loss and danger. High ratings of entrapment predicted only onsets of mixed episodes. The loss categories of death and respondent-initiated separation predicted pure MD but not pure GAS episodes. Events with a combination of humiliation (especially other-initiated separation) and loss were more depressogenic than pure loss events, including death. No sex differences were seen in the prediction of episodes of illness by event categories. CONCLUSIONS: In addition to loss, humiliating events that directly devalue an individual in a core role were strongly linked to risk for depressive episodes. Event dimensions and categories that predispose to pure MD vs pure GAS episodes can be distinguished with moderate specificity. The event dimensions that preceded mixed MD-GAS episodes were largely the sum of those that preceded pure MD and pure GAS episodes.

Published online before print June 5, 2003
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0732061100

Neuroscience
Reset of human neocortical oscillations during a working memory task

D. S. Rizzuto *, J. R. Madsen , E. B. Bromfield ¶, A. Schulze-Bonhage ||, D.
Seelig *, R. Aschenbrenner-Scheibe ||, and M. J. Kahana ***
*Volen Center for Complex Systems, Brandeis University, Waltham, MA 02454;
Department of Neurosurgery, Children's Hospital, Boston, MA 02115; Department
of Surgery, Harvard Medical School, Boston, MA 02115; ¶Department of Neurology,
Brigham and Women's Hospital, Boston, MA 02115; and ||Neurozentrum,
Universitaet Freiburg, D-79106 Freiburg, Germany

Communicated by Saul Sternberg, University of Pennsylvania, Philadelphia, PA,
April 8, 2003 (received for review May 22, 2002)

Both amplitude and phase of rhythmic slow-wave electroencephalographic activity
are physiological correlates of learning and memory in rodents. In humans,
oscillatory amplitude has been shown to correlate with memory; however, the
role of oscillatory phase in human memory is unknown. We recorded intracranial
electroencephalogram from human cortical and hippocampal areas while subjects
performed a short-term recognition memory task. On each trial, a series of four
list items was presented followed by a memory probe. We found agreement across
trials of the phase of oscillations in the 7- to 16-Hz range after randomly
timed stimulus events, evidence that these events either caused a phase shift
in the underlying oscillation or initiated a new oscillation. Phase locking in
this frequency range was not generally associated with increased poststimulus
power, suggesting that stimulus events reset the phase of ongoing oscillations.
Different stimulus classes selectively modulated this phase reset effect, with
topographically distinct sets of recording sites exhibiting preferential reset
to either probe items or to list items. These findings implicate the reset of
brain oscillations in human working memory.

Does the cerebellum contribute to specific aspects of attention?

Birgit Gottwald, , Zoran Mihajlovic, Barbara Wilde and Hubertus Maximilian Mehdorn

Neuropsychologia

Volume 41, Issue 11 , 2003, Pages 1452-1460

Abstract

We present data on attentional and neuropsychological functions of 16 patients with focal cerebellar lesions (13 tumours, 3 haematomas) compared to normative test data, and to 11 control subjects matched for age, gender, and years of education. Patients showed distinct deficits in qualitative aspects of a divided attention task, and in a working memory task. Performance in selective attention was unimpaired. The results support the concept that the cerebellum plays a role not only in motor, but also in higher cognitive functions. They are discussed on the basis of the idea that prediction and preparation are fundamental functions of the cerebellum. Therefore, the results confirm the idea that cerebellar lesions lead to reduced performance in specific attention tasks.

<<IDM - gets into the issues of precision - dopamine shows ties to integration WITHIN a differentiation, linking of parts to assert a whole etc,fine motor control etc etc >>

Conscious control over the content of unconscious cognition

Wilfried Kunde, Andrea Kiesel and Joachim Hoffmann

Cognition

Volume 88, Issue 2 , June 2003, Pages 223-242

Abstract

Visual stimuli (primes) presented too briefly to be consciously identified can nevertheless affect responses to subsequent stimuli – an instance of unconscious cognition. There is a lively debate as to whether such priming effects originate from unconscious semantic processing of the primes or from reactivation of learned motor responses that conscious stimuli afford during preceding practice. In four experiments we demonstrate that unconscious stimuli owe their impact neither to automatic semantic categorization nor to memory traces of preceding stimulus-response episodes, but to their match with pre-specified cognitive action-trigger conditions. The intentional creation of such triggers allows actors to control the way unconscious stimuli bias their behaviour.

Dissociable neural systems for recognizing emotions

- Ralph Adolphs, Daniel Tranel and Antonio R. Damasio

Brain and Cognition

Volume 52, Issue 1 , June 2003, Pages 61-69

Abstract

This study tested the hypothesis that the recognition of emotions would draw upon anatomically separable brain regions, depending on whether the stimuli were static or explicitly conveyed information regarding actions. We investigated the hypothesis in a rare subject with extensive bilateral brain lesions, patient B., by administering tasks that assessed recognition and naming of emotions from visual and verbal stimuli, some of which depicted actions and some of which did not. B. could not recognize any primary emotion other than happiness, when emotions were shown as static images or given as single verbal labels. By contrast, with the notable exception of disgust, he correctly recognized primary emotions from dynamic displays of facial expressions as well as from stories that described actions. Our findings are consistent with the idea that information about actions is processed in occipitoparietal and dorsal frontal cortices, all of which are intact in B.'s brain. Such information subsequently would be linked to knowledge about emotions that depends on structures mapping somatic states, many of which are also intact in B.'s brain. However, one of these somatosensory structures, the insula, is bilaterally damaged, perhaps accounting for B.'s uniformly impaired recognition of disgust (from both static and action stimuli). Other structures that are damaged in B.'s brain, including bilateral inferior and anterior temporal lobe and medial frontal cortices, appear to be critical for linking perception of static stimuli to recognition of emotions. Thus the retrieval of knowledge regarding emotions draws upon widely distributed and partly distinct sets of neural structures, depending on the attributes of the stimulus.

Brain Res Bull. 2003 May 30;60(4):387-93.

The evolution of mammalian cortex, from lamination to arealization.

Montagnini A, Treves A.

SISSA-Programme in Neuroscience, via Beirut 4, 34014, Trieste, Italy

We analyse some of the most important anatomical and functional features emerging at different stages of mammalian brain evolution in terms of a possible computational advantage. At the transition from reptiles to mammals, a major anatomical change occurs in the originally sensory dorsal cortex. The principal layer of pyramidal cells is split by the insertion of a new layer of granule cells, giving rise to the laminated isocortex. It has been hypothesized that this qualitative change in the evolution of mammalian brains is necessary to support fine topography in their sensory maps. The simulation of neural network models demonstrates that a nonlaminated patch of cortex must compromise between transmitting "where" information, explicitly mapped, topographically, on the cortical sheet, and retrieving "what" information, represented by the distributed firing pattern across neurons. The differentiation of a granular layer is shown in the model to yield a small quantitative advantage, allowing to transmit a slightly better combination of both information types.Along the same theoretical lines, we are investigating the multiplication of successive sensory areas coding for ever more composite stimuli, such as those in the visual and auditory temporal cortices in primates. In particular we analyse the possible computational advantage for a specific neural population devoted to encode the complex structure of whole stimuli, rather than relying on the coactivation of separate populations encoding their basic elements.

Cell. 2003 Feb 7;112(3):293-301.

Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways.

Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ.

Howard Hughes Medical Institute, Department of Biology, University of California, San Diego, La Jolla, CA 92093, USA.

Mammals can taste a wide repertoire of chemosensory stimuli. Two unrelated families of receptors (T1Rs and T2Rs) mediate responses to sweet, amino acids, and bitter compounds. Here, we demonstrate that knockouts of TRPM5, a taste TRP ion channel, or PLCbeta2, a phospholipase C selectively expressed in taste tissue, abolish sweet, amino acid, and bitter taste reception, but do not impact sour or salty tastes. Therefore, despite relying on different receptors, sweet, amino acid, and bitter transduction converge on common signaling molecules. Using PLCbeta2 taste-blind animals, we then examined a fundamental question in taste perception: how taste modalities are encoded at the cellular level. Mice engineered to rescue PLCbeta2 function exclusively in bitter-receptor expressing cells respond normally to bitter tastants but do not taste sweet or amino acid stimuli. Thus, bitter is encoded independently of sweet and amino acids, and taste receptor cells are not broadly tuned across these modalities.

J Neurophysiol 2002 Jun;87(6):2715-25

Stimulus-related gamma oscillations in primate auditory cortex.

Brosch M, Budinger E, Scheich H.

Leibniz-Institut fur Neurobiologie, 39118 Magdeburg, Germany. brosch@ifn-magdeburg.de

With a multielectrode system, we explored neuronal activity in the gamma range (>40 Hz) in the primary and caudomedial auditory cortex of six anesthetized macaque monkeys. Stimuli were tone bursts of 100- to 500-ms duration that were presented at sound pressure levels of 40-60 dB and were varied over a wide range of frequencies. These stimuli induced gamma oscillations, not phase-locked to the onset of stimulation, in 465 of 616 multiunit clusters and at 321 of 422 sites at which field potentials were recorded. Occurrence of gamma activity was stimulus dependent. It was mostly seen when the stimulus was at the units' preferred frequency. The incidence of gamma activity decreased with increasing difference between stimulus frequency and preferred frequency. gamma activity emerged 100-900 ms after stimulus onset with highest incidence ~120 ms. Amplitudes of stimulus-induced gamma oscillations in field potentials were, on average, almost twice the amplitude of spontaneously occurring gamma oscillations. gamma activity at different sites within the primary and the caudomedial auditory field could be synchronized at near-zero phase. Synchrony depended on the spatial distance and on the receptive fields similarity of pairs of units. It decreased with increasing distance between recording sites and increased with similarity of preferred frequencies of the pairs of units. The results indicate that stimulus-induced gamma oscillations originate from sources in the auditory cortex. They further suggest that gamma oscillations may provide a mechanism utilized in many parts of the sensory cortex, including the auditory cortex, to integrate neurons according to the similarity of their receptive fields.

International Journal of Bifurcation and Chaos, Vol. 13, No. 1 (2003) 7-18

WHEN TWO COUPLED PENDULUMS EQUAL ONE: A SYNCHRONIZATION MACHINE

H. J. T. SMITH
Department of Physics, University of Waterloo, Ontario, Canada

JAMES A. BLACKBURN
Department of Physics and Computing, Wilfrid Laurier University, Waterloo, Ontario, Canada

GREGORY L. BAKER
Division of Mathematics and Science, Bryn Athyn College of the New Church, Bryn Athyn, PA 19009, USA
We show that two coupled pendulums that are coupled and can synchronize, are mathematically equivalent to one "horizontal" parametrically driven pendulum. We have fabricated a horizontal pendulum and present data from this horizontal pendulum which we believe to be the first physical realization of such a mechanical "synchronization machine." A description of intermittent synchronization that can occur when two coupled pendulums are in a chaotic state is given in terms of the data from the horizontal pendulum. We discuss the relationship between the modes of the horizontal pendulum and the corresponding synchronization of the two coupled pendulums. Finally, we show that when a horizontal pendulum is driven by any random source, not necessarily chaotic, intermittent synchronization can occur.

Keywords: Pendulum; synchronization; chaos.

Brain Res Brain Res Rev 2002 Jun;39(1):1-28

The neurophysics of consciousness.

John ER.

Brain Research Laboratories, NYU School of Medicine, 550 First Avenue, New York 10016, USA. roy@br14.med.nyu.edu

Consciousness combines information about attributes of the present multimodal sensory environment with relevant elements of the past. Information from each modality is continuously fractionated into distinct features, processed locally by different brain regions relatively specialized for extracting these disparate components and globally by interactions among these regions. Information is represented by levels of synchronization within neuronal populations and of coherence among multiple brain regions that deviate from random fluctuations. Significant deviations constitute local and global negative entropy, or information. Local field potentials reflect the degree of synchronization among the neurons of the local ensembles. Large-scale integration, or 'binding', is proposed to involve oscillations of local field potentials that play an important role in facilitating synchronization and coherence, assessed by neuronal coincidence detectors, and parsed into perceptual frames by cortico-thalamo-cortical loops. The most probable baseline levels of local synchrony, coherent interactions among brain regions, and frame durations have been quantitatively described in large studies of their age-appropriate normative distributions and are considered as an approximation to a conscious 'ground state'. The level of consciousness during anesthesia can be accurately predicted by the magnitude and direction of reversible multivariate deviations from this ground state. An invariant set of changes takes place during anesthesia, independent of the particular anesthetic agent. Evidence from a variety of neuroscience areas supporting these propositions, together with the invariant reversible electrophysiological changes observed with loss and return of consciousness, are used to provide a foundation for this theory of consciousness. This paper illustrates the increasingly recognized need to consider global as well as local processes in the search for better explanations of how the brain accomplishes the transformation from synchronous and distributed neuronal discharges to seamless global subjective awareness.

J Neurophysiol 2002 Apr;87(4):1993-2008

GABAergic and glutamatergic modulation of spontaneous and motor-cortex-evoked complex spike activity.

Lang EJ.

Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA. Lange01@popmail.med.nyu.edu

Olivocerebellar activity is organized such that synchronous complex spikes occur primarily among Purkinje cells located within the same parasagittally oriented strip of cortex. Previous findings have shown that this synchrony distribution is modulated by the release of GABA and glutamate within the inferior olive, which probably act by controlling the efficacy of the electrotonic coupling between olivary neurons. The relative strengths of these two neurotransmitters in modulating the patterns of synchrony were compared by obtaining multiple electrode recordings of spontaneous crus 2a complex spike activity during intraolivary injection of solutions containing a GABA(A) (picrotoxin) and/or AMPA [1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX)] receptor antagonist. Injection of either antagonist led to increased synchrony between cells located within the same parasagittally oriented approximately 250-microm-wide cortical strip. Picrotoxin also increased complex spike synchrony among cells located in different cortical strips, leading to a less prominent banding pattern, whereas injections of NBQX tended to decrease complex spike synchrony among such cells, enhancing the banding pattern. The relative strength of these two classes of olivary afferents was assessed by first injecting one of the antagonists alone and then in combination with the other. The enhanced banding pattern of complex spike synchrony following injection of NBQX alone remained during the subsequent combined injection of both antagonists. Furthermore, the widespread synchronization of complex spike activity following injection of picrotoxin alone was partially or completely reversed by combined injection of picrotoxin and NBQX. Changes in the climbing fiber reflex induced by the intraolivary injections paralleled the changes observed for spontaneous complex spike activity, indicating that the effects of picrotoxin and NBQX on the synchrony distribution reflect changes in the pattern of effective coupling of inferior olivary neurons and demonstrating that synchronous complex spike activity does not require simultaneous excitatory input to olivary cells. Finally the pattern of synchrony during motor cortical stimulation was examined. It was found that the patterns of synchrony for motor-cortex-evoked complex spike activity were similar to those of spontaneous activity, indicating an important role for electrotonic coupling in determining the response of the olivocerebellar system to afferent input. Moreover, intraolivary injections of picrotoxin increased the spatial distribution of the evoked response. In sum, the results provide evidence for the hypothesis that electrotonic coupling of inferior olivary neurons via gap junctions is the mechanism underlying complex spike synchrony and that this coupling plays an important role in determining the responses of the olivocerebellar system to synaptic input.

J Neurosci 2002 Feb 1;22(3):1002-9

Electrical synapses in the thalamic reticular nucleus.

Landisman CE, Long MA, Beierlein M, Deans MR, Paul DL, Connors BW.

Department of Neuroscience, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA.

Neurons of the thalamic reticular nucleus (TRN) provide inhibitory input to thalamic relay cells and generate synchronized activity during sleep and seizures. It is widely assumed that TRN cells interact only via chemical synaptic connections. However, we show that many neighboring pairs of TRN neurons in rats and mice are electrically coupled. In paired-cell recordings, electrical synapses were able to mediate close correlations between action potentials when the coupling was strong; they could modulate burst-firing states even when the coupling strength was more modest. Electrical synapses between TRN neurons were absent in mice with a null mutation for the connexin36 (Cx36) gene. Surprisingly, inhibitory chemical synaptic connections between pairs of neurons were not observed, although strong extracellular stimuli could evoke inhibition in single TRN neurons. We conclude that Cx36-dependent gap junctions play an important role in the regulation of neural firing patterns within the TRN. When combined with recent observations from the cerebral cortex, our results imply that electrical synapses are a common mechanism for generating synchrony within networks of inhibitory neurons in the mammalian forebrain.

J Neurophysiol 2002 Mar;87(3):1526-41

Electrical coupling between model midbrain dopamine neurons: effects on firing pattern and synchrony.

Komendantov AO, Canavier CC.

Department of Psychology, University of New Orleans, New Orleans, LA 70148, USA.

The role of gap junctions between midbrain dopamine (DA) neurons in mechanisms of firing pattern generation and synchronization has not been well characterized experimentally. We modified a multi-compartment model of DA neuron by adding a spike-generating mechanism and electrically coupling the dendrites of two such neurons through gap junctions. The burst-generating mechanism in the model neuron results from the interaction of a N-methyl-D-aspartate (NMDA)-induced current and the sodium pump. The firing patterns exhibited by the two model neurons included low frequency (2-7 Hz) spiking, high-frequency (13-20 Hz) spiking, irregular spiking, regular bursting, irregular bursting, and leader/follower bursting, depending on the parameter values used for the permeability for NMDA-induced current and the conductance for electrical coupling. All of these firing patterns have been observed in physiological neurons, but a systematic dependence of the firing pattern on the covariation of these two parameters has not been established experimentally. Our simulations indicate that electrical coupling facilitates NMDA-induced burst firing via two mechanisms. The first can be observed in a pair of identical cells. At low frequencies (low NMDA), as coupling strength was increased, only a transition from asynchronous to synchronous single-spike firing was observed. At high frequencies (high NMDA), increasing the strength of the electrical coupling in an identical pair resulted in a transition from high-frequency single-spike firing to burst firing, and further increases led to synchronous high-frequency spiking. Weak electrical coupling destabilizes the synchronous solution of the fast spiking subsystems, and in the presence of a slowly varying sodium concentration, the desynchronized spiking solution leads to bursts that are approximately in phase with spikes that are not in phase. Thus this transitional mechanism depends critically on action potential dynamics. The second mechanism for the induction of burst firing requires a heterogeneous pair that is, respectively, too depolarized and too hyperpolarized to burst. The net effect of the coupling is to bias at least one cell into an endogenously burst firing regime. In this case, action potential dynamics are not critical to the transitional mechanism. If electrical coupling is indeed more prominent in vivo due to basal level of modulation of gap junctions in vivo, these results may indicate why NMDA-induced burst firing is easier to observe in vivo as compared in vitro.

Neurosci Lett 2003 Jan 9;336(1):33-6

Scale-invariant fluctuations of the dynamical synchronization in human brain electrical activity.

Gong P, Nikolaev AR, van Leeuwen C.

Laboratory for Perceptual Dynamics, Riken, Brain Science Institute, 2-1, Hirosawa, Wako-shi, Saitama, 351-0198, Japan. plgong@brain.riken.go.jp

The dynamical properties of large-scale, long-term phase synchronization behavior in the alpha range of electroencephalographic signals were investigated. We observed dynamical phase synchronization and presented evidence of an underlying spatiotemporal ordering. Fluctuations in the duration of episodes of intermittent synchrony are scale-invariant. Moreover, the exponent used to describe this behavior is stable across different normal subjects. The results provide a new feature of self-organization in human brain activity and constitute a quantitative basis for modeling its dynamics.
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Epilepsia 2002 Jun;43(6):574-80

Cooling abolishes neuronal network synchronization in rat hippocampal slices.

Javedan SP, Fisher RS, Eder HG, Smith K, Wu J.

Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013, USA.

PURPOSE: We sought to determine whether cooling brain tissue from 34 to 21 degrees C could abolish tetany-induced neuronal network synchronization (gamma oscillations) without blocking normal synaptic transmission. METHODS: Intracellular and extracellular electrodes recorded activity in transverse hippocampal slices (450-500 microm) from Sprague-Dawley male rats, maintained in an air-fluid interface chamber. Gamma oscillations were evoked by afferent stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber was 34 degrees C, reduced to 21 degrees C within 20 min. RESULTS: Suprathreshold tetanic stimuli evoked membrane potential oscillations in the 40-Hz frequency range (n = 21). Gamma oscillations induced by tetanic stimulation were blocked by bicuculline, a gamma-aminobutyric acid (GABA)A-receptor antagonist. Cooling from 34 to 21 degrees C reversibly abolished gamma oscillations in all slices tested. Short, low-frequency discharges persisted after cooling in six of 14 slices. Single-pulse-evoked potentials, however, were preserved after cooling in all cases. Latency between stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r = 0.77). Tetanic stimulation at high intensity elicited not only gamma oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma oscillation and abolished epileptiform bursts in a reversible manner. CONCLUSIONS: Tetany-induced neuronal network synchronization by GABAA-sensitive gamma oscillations is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses transition from gamma oscillation to ictal bursting at higher stimulus intensities. These findings suggest that cooling may disrupt network synchrony necessary for epileptiform activity.

Nature 2002 Nov 14;420(6912):168-71

Synchronization of animal population dynamics by large-scale climate.

Post E, Forchhammer MC.

Department of Biology, The Pennsylvania State University, 208 Mueller Lab, University Park, Pennsylvania 16802, USA. esp10@psu.edu

The hypothesis that animal population dynamics may be synchronized by climate is highly relevant in the context of climate change because it suggests that several populations might respond simultaneously to climatic trends if their dynamics are entrained by environmental correlation. The dynamics of many species throughout the Northern Hemisphere are influenced by a single large-scale climate system, the North Atlantic Oscillation (NAO), which exerts highly correlated regional effects on local weather. But efforts to attribute synchronous fluctuations of contiguous populations to large-scale climate are confounded by the synchronizing influences of dispersal or trophic interactions. Here we report that the dynamics of caribou and musk oxen on opposite coasts of Greenland show spatial synchrony among populations of both species that correlates with the NAO index. Our analysis shows that the NAO has an influence in the high degree of cross-species synchrony between pairs of caribou and musk oxen populations separated by a minimum of 1,000 km of inland ice. The vast distances, and complete physical and ecological separation of these species, rule out spatial coupling by dispersal or interaction. These results indicate that animal populations of different species may respond synchronously to global climate change over large regions.

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Biosystems 2002 Oct-Dec;67(1-3):139-46

Firing coincidences between neighboring retinal ganglion cells: inside information or epiphenomenon?

Levine MW, Castaldo K, Kasapoglu MB.

Department of Psychology, M/C 285, University of Illinois at Chicago, 1007 West Harrison Street, 60607, Chicago, IL, USA

Retinal ganglion cells often fire impulses in synchrony; is this synchronization an irrelevant by-product of processing shared inputs, or does it encode information? We examined the rate of occurrence of coincident impulses from pairs of ganglion cells responding to stimuli that varied along several dimensions. We find that coincidences convey little if any additional information about simple static stimuli beyond what could be determined from the firing rates of the two cells considered separately. In fact, at least one of the separate cells generally provided a better information channel than the coincidence rate, implying that under these conditions ganglion cells do not employ a strategy of encoding by coincidences.

J Neurosci 2002 Dec 15;22(24):10898-905

Rhythmicity without synchrony in the electrically uncoupled inferior olive.

Long MA, Deans MR, Paul DL, Connors BW.

Department of Neuroscience, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA.

Neurons of the inferior olivary nucleus (IO) form the climbing fibers that excite Purkinje cells of the cerebellar cortex. IO neurons are electrically coupled through gap junctions, and they generate synchronous, subthreshold oscillations of membrane potential at approximately 5-10 Hz. Experimental and theoretical studies have suggested that both the rhythmicity and synchrony of IO neurons require electrical coupling. We recorded from pairs of IO neurons in slices of mouse brainstem in vitro. Most pairs of neurons from wild-type (WT) mice were electrically coupled, but coupling was rare and weak between neurons of knock-out (KO) mice for connexin36, a neuronal gap junction protein. IO cells in both WT and KO mice generated rhythmic membrane fluctuations of similar frequency and amplitude. Oscillations in neighboring pairs of WT neurons were strongly synchronized, whereas the oscillations of KO pairs were uncorrelated. Spontaneous oscillations in KO neurons were not blocked by tetrodotoxin. Spontaneously oscillating neurons of both WT and KO mice generated occasional action potentials in phase with their membrane rhythms, but only the action potentials of WT neuron pairs were synchronous. Harmaline, a beta-carboline derivative thought to induce tremor by facilitating rhythmogenesis in the IO, was injected systemically into WT and KO mice. Harmaline-induced tremors were robust and indistinguishable in the two genotypes, suggesting that gap junction-mediated synchrony does not play a role in harmaline-induced tremor. We conclude that electrical coupling is not necessary for the generation of spontaneous subthreshold oscillations in single IO neurons, but that coupling can serve to synchronize rhythmic activity among IO neurons.

Percept Mot Skills 2002 Dec;95(3 Pt 1):1013-26

The Mozart effect may only be demonstrable in nonmusicians.

Twomey A, Esgate A.

University of Westminster, London, UK.

The "Mozart effect" is the tendency to score higher on spatiotemporal IQ subscales following exposure to complex music such as Mozart's Sonata K.448. This phenomenon was investigated in 20 musicians and 20 nonmusicians. The trion model predicts increased synchrony between musical and spatiotemporal centres in the right cerebral hemisphere. Since increased left-hemispheric involvement in music processing occurs as a result of music training, predictions deriving from the possibility of increased synchrony with left-hemispheric areas in musicians were tested. These included improved performance on language as well as spatiotemporal tasks. Spatiotemporal, synonym generation, and rhyming word generation tasks were employed as was the Mozart Sonata K.448. A Mozart effect was demonstrated on the spatiotemporal task, and the facilitatory effect of exposure to Mozart was greater for the nonmusician group. This finding adds to the robustness of the Mozart effect since novel tasks were used. No Mozart effect was found for either group on the verbal tasks, although the musicians scored higher on rhyming word generation. This new finding adds to the number of nonmusical tasks apparently showing long-term benefits from music training. However, no systematic link was found between performance on any task and number of years spent in music training. The failure to induce a Mozart effect in the musician group on verbal tasks, as well as that group's limited facilitation on spatiotemporal tasks, may be associated with either a ceiling effect due to the long-term effects of music training or from methodological factors. Both possibilities are discussed.

Brain Res Brain Res Rev 2003 Jan;41(1):57-78

Synchronous gamma activity: a review and contribution to an integrative neuroscience model of schizophrenia.

Lee KH, Williams LM, Breakspear M, Gordon E.

Cognitive Neuroscience Unit, Department of Psychology, University of Sydney, and The Brain Dynamics Centre, Westmead Hospital, 2145, Sydney, NSW, Australia.

Synchronous high frequency (Gamma band) activity has been proposed as a candidate mechanism for the integration or 'binding' of distributed brain activities. Since the first descriptions of schizophrenia, attempts to characterize this disorder have focused on disturbances in such integrative processing. Here, we review both micro- and macroscopic neuroscience research into Gamma synchrony, and its application to understanding schizophrenia. The review encompasses evidence from both animal and human studies for the functional significance of Gamma activity, the association between Gamma dysfunction and information processing disturbances, and the relevance of specific Gamma dysfunctions to the integration and extension of previous disconnection models of schizophrenia. Attention is given to the relationship between Gamma activity and the heterogeneous symptoms of schizophrenia. Existing studies show that measures of Gamma activity have the potential to explain far more of the variance in schizophrenia performance than previous neurophysiological measures. It is concluded that measures of Gamma synchrony offer a valuable window into the core integrative disturbance in schizophrenia cognition.

(IDM FOCUS - gamma functions like a system clock, irregular timing leads to anomolies in encoding/decoding)

Clin Neurophysiol 2002 Oct;113(10):1640-6

Is 'gamma' (40 Hz) synchronous activity disturbed in patients with traumatic brain injury?

Slewa-Younan S, Green AM, Baguley IJ, Felmingham KL, Haig AR, Gordon E.

Brain Injury Rehabilitation Service, Westmead Hospital, PO Box 533, Wentworthville, NSW, 2145, Australia. shameran@biru.wsahs.nsw.gov.au

OBJECTIVES: The objective of this work is to determine whether Gamma (40 Hz) synchronous activity has disturbed patients with severe traumatic brain injury (TBI).METHODS: Using a conventional auditory oddball paradigm, the extent of Gamma synchrony across multiple scalp sites in specific frequency bands as a function of time was examined in 15 patients with severe TBI and 15 age- and sex-matched controls. Averaged Gamma synchrony was analyzed using within and between group multiple analyses of variance with region (left versus right hemisphere, anterior versus posterior region) as the within factor.RESULTS: Compared to controls, subjects with TBI displayed significantly delayed early Gamma latency (from -150 to 150 ms) (F((1,28))=10.28, P<0.003) across all sites in addition to other specific regional disturbances. For late Gamma synchrony, subjects with TBI displayed delayed Gamma latency at the left hemisphere (from 200 to 450 ms) (F((1,28))=8.71, P<0.006) and posterior region (F((1,28))=9.18, P<0.006) in comparison to controls.CONCLUSIONS: Impaired integration of spatially distributed brain activity ('40 Hz' electroencephalogram rhythms) may be an important marker of deficits of cortical network binding postulated to be abnormal in people who have survived TBI.

Naturwissenschaften 2002 Jul;89(7):316-8

Inter-cellular spike coincidences in visual detection tasks.

Bauer R, Heinze S.

FB Physik/Neurophysik, Philipps-Universitat, Marburg, Germany. roman.bauer@physik.uni-marburg.de

Synchronized spike activity is discussed as a possible representational code for object integration and as a neuronal basis of attention, perception and awareness. As a byproduct of experiments in which monkeys were trained to detect simple figures composed of single Gabor patches in a noisy background of similar elements, we found in special cases increased spike synchrony above chance level specifically related to figure detection. The long latency of this effect is difficult to interpret. It may be a sign of the cognitive state of an animal when it perceives the figure.
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: J Neurosci 2002 Jul 1;22(13):5694-704

Sleep states differentiate single neuron activity recorded from human epileptic hippocampus, entorhinal cortex, and subiculum.

Staba RJ, Wilson CL, Bragin A, Fried I, Engel J Jr.

Department of Neurobiology, David Greffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095, USA.

Animal models of epilepsy have shown that synchronous burst firing is associated with epileptogenesis, yet the evidence from human studies linking neuronal synchrony and burst firing to epileptogenesis remains equivocal. Sleep-wake states have been shown to differentially modulate the generation of epileptiform EEG spikes between brain regions of greater and lesser seizure-generating potential, providing information that helps to identify the primary epileptogenic region. Using these state-dependent mechanisms to assist us in identifying neuronal correlates of human epilepsy, we recorded interictal neuronal activity from mesial temporal lobe (MTL) areas in epileptic patients implanted with depth electrodes required for medical diagnosis during polysomnographically defined sleep-wake states. Results show that single neurons recorded ipsilateral to seizure-initiating MTL ("epileptic") areas had significantly higher firing rates (p = 0.01) and burst propensity (p = 0.01) and greater synchrony of discharges (p = 0.003) compared with neurons recorded from contralateral non-seizure-generating MTL ("non-epileptic") areas. In particular, during episodes of slow wave sleep (SWS) and rapid eye movement (REM) sleep, epileptic hippocampal neurons had significantly higher burst rates compared with non-epileptic hippocampal neurons (both p = 0.01). In contrast, during episodes of wakefulness (Aw), no difference in burst firing between epileptic and non-epileptic hippocampal neurons was observed. Furthermore, synchronous firing was significantly higher between epileptic MTL neurons compared with non-epileptic MTL neurons during SWS (p = 0.04) and REM sleep (p = 0.02), but no difference in neuronal synchrony was found between epileptic and non-epileptic neurons during Aw. These results provide evidence that sleep states differentially modulate abnormal epileptogenic neuronal discharge properties within human MTL and confirm that neuronal burst firing and enhanced neuronal synchrony observed in experimental animal models of epilepsy characterizes human epilepsy as well.
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J Neurosci 2002 Jun 1;22(11):4639-53

Enhanced synchrony among primary motor cortex neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease.

Goldberg JA, Boraud T, Maraton S, Haber SN, Vaadia E, Bergman H.

Department of Physiology, The Hebrew University-Hadassah Medical School, the Interdisciplinary Center for Neural Computation, The Hebrew University, Jerusalem 91120, Israel. joshg@md.huji.ac.il

Primary motor cortex (MI) neurons discharge vigorously during voluntary movement. A cardinal symptom of Parkinson's disease (PD) is poverty of movement (akinesia). Current models of PD thus hypothesize that increased inhibitory pallidal output reduces firing rates in frontal cortex, including MI, resulting in akinesia and muscle rigidity. We recorded the simultaneous spontaneous discharge of several neurons in the arm-related area of MI of two monkeys and in the globus pallidus (GP) of one of the two. Accelerometers were fastened to the forelimbs to detect movement, and surface electromyograms were recorded from the contralateral arm of one monkey. The recordings were conducted before and after systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rendering the animals severely akinetic and rigid with little or no tremor. The mean spontaneous MI rates during periods of immobility (four to five spikes/sec) did not change after MPTP; however, in this parkinsonian state, MI neurons discharged in long bursts (sometimes >2 sec long). These bursts were synchronized across many cells but failed to elicit detectable movement, indicating that even robust synchronous MI discharge need not result in movement. These synchronized population bursts were absent from the GP and were on a larger timescale than oscillatory synchrony found in the GP of tremulous MPTP primates, suggesting that MI parkinsonian synchrony arises independently of basal ganglia dynamics. After MPTP, MI neurons responded more vigorously and with less specificity to passive limb movement. Abnormal MI firing patterns and synchronization, rather than reduced firing rates, may underlie PD akinesia and persistent muscle rigidity.

Ann N Y Acad Sci 2002 Dec;978:164-74

Temporal organization of activity in the cerebellar cortex: a manifesto for synchrony.

Isope P, Dieudonne S, Barbour B.

Laboratoire de Neurobiologie (CNRS UMR 8544), Ecole Normale Superieure, 75230 Paris Cedex 05, France.

The issues of temporal coding and the temporal organization of activity have aroused a great deal of interest in sensory systems, cortex, thalamus, and hippocampus. Strangely, despite the important timing roles attributed to the cerebellum, little consideration has been given to the organization of activity within the cerebellar circuitry. In fact, there is evidence of a remarkable temporal patterning of activity in even the earliest cerebellar recordings. The evidence for the existence of high-frequency oscillations in the cerebellar cortex is reviewed and possible mechanisms are discussed; one involves the synchrony of parallel fiber inputs to Purkinje cells. It is shown how synchronous and oscillatory activity can enable extremely precise timing and also how they can maximize the information storage capacity of the cerebellar cortex.

AJNR Am J Neuroradiol 2003 Feb;24(2):208-12

Role of the corpus callosum in functional connectivity.

Quigley M, Cordes D, Turski P, Moritz C, Haughton V, Seth R, Meyerand ME.

Department of Medical Physics, University of Wisconsin-Madison, 1300 University Avenue, 1530 MSC, Madison, WI 53706, USA.

BACKGROUND AND PURPOSE: Regional cerebral blood flow fluctuates synchronously in corresponding brain regions between the hemispheres. This synchrony implies neuronal connections between brain regions. The synchrony of blood flow changes is defined operationally as functional connectivity. Our purpose was to measure functional connectivity in patients with corpus callosal agenesis, in whom the interhemispheric connectivity is hypothetically diminished. METHODS: In three patients with agenesis of the corpus callosum, functional MR imaging was performed while patients performed text-listening and finger-tapping tasks. Functional images were also acquired while the patients performed no specific task (resting state). Regions of activation temporally correlated with the performance of the tasks were identified by cross-correlating the task data with a reference function. Voxel clusters (seed voxels) that corresponded to regions of activation in the task-activation data set were selected in the resting data set. All the voxels in the resting 3D data set that had a correlation coefficient exceeding 0.4 were identified. The number of these voxels in the ipsilateral and contralateral hemispheres was tabulated. RESULTS: In all patients, technically adequate functional MR and functional connectivity MR maps were obtained. For both tasks, activation was found in both hemispheres. For all of the seed voxels, significantly more functionally connected voxels were found in the ipsilateral hemisphere than in the contralateral hemisphere. For most seed voxels, no functionally connected voxels were found in the contralateral hemisphere. CONCLUSION: Interhemispheric functional connectivity in the motor and auditory cortices is diminished in patients with agenesis of the corpus callosum compared with that of healthy subjects.

Life Sci Space Res 1977;15:233-7

The effect of low light intensity on the maintenance of circadian synchrony in human subjects.

Winget CM, Lyman J, Beljan JR.

Biomedical Research Division, NASA, Ames Research Center, Moffett Field, Calif, USA.

The light-intensity threshold for humans is not known. In past space flights owing to power restrictions, light intensities have been minimal and reported to be as low as 15 ft. c. This study was conducted to determine whether the light (L)/dark (D) environment of 16L : 8D at the relatively low light intensity of 15 ft. c. was adequate for the maintenance of circadian synchrony in human subjects. Six healthy male subjects aged 20-23 years were exposed for 21 days to a 16L : 8D photoperiod. During the first 7 days the light intensity was 100 ft. c.; it was reduced to 15 ft. c. during the next 7 days and increased again to 100 ft. c. during the last 7 days of the study. Rectal temperature (RT) and heart rate (HR) were recorded continuously throughout the 21 days of the study. In the 100 ft.c. 16L : 8D the RT and HR rhythms remained stable and circadian throughout. When the light intensity was decreased to 15 ft.c. the periodicity of the HR rhythm was significantly decreased and this rhythm showed marked instability. In contrast the period of the RT rhythm did not change but a consistent phase delay occurred due to a delay in the lights-on associated rise in RT. These divergent effects on these two rhythms in internal desynchronization and performance decrement during the 15 ft.c. exposure. The data emphasize the need for establishing accurately the minimal lighting requirements for the maintenance of circadian rhythms of humans in confined environments.

Neural Comput 2003 Mar;15(3):509-38

Synchronization in networks of excitatory and inhibitory neurons with sparse, random connectivity.

Borgers C, Kopell N.

Department of Mathematics, Tufts University, Medford, MA 02155, U.S.A. chritopher.borgers@tufts.edu

In model networks of E-cells and I-cells (excitatory and inhibitory neurons, respectively), synchronous rhythmic spiking often comes about from the interplay between the two cell groups: the E-cells synchronize the I-cells and vice versa. Under ideal conditions-homogeneity in relevant network parameters and all-to-all connectivity, for instance-this mechanism can yield perfect synchronization. We find that approximate, imperfect synchronization is possible even with very sparse, random connectivity. The crucial quantity is the expected number of inputs per cell. As long as it is large enough (more precisely, as long as the variance of the total number of synaptic inputs per cell is small enough), tight synchronization is possible. The desynchronizing effect of random connectivity can be reduced by strengthening the E --> I synapses. More surprising, it cannot be reduced by strengthening the I --> E synapses. However, the decay time constant of inhibition plays an important role. Faster decay yields tighter synchrony. In particular, in models in which the inhibitory synapses are assumed to be instantaneous, the effects of sparse, random connectivity cannot be seen.

Philos Trans R Soc Lond B Biol Sci 2002 Dec 29;357(1428):1659-73

Thalamic circuitry and thalamocortical synchrony.

Jones EG.

Center for Neuroscience, University of California, Davis, Davis, CA 95616, USA. ejones@ucdavis.edu

The corticothalamic system has an important role in synchronizing the activities of thalamic and cortical neurons. Numerically, its synapses dominate the inputs to relay cells and to the gamma-amino butyric acid (GABA)ergic cells of the reticular nucleus (RTN). The capacity of relay neurons to operate in different voltage-dependent functional modes determines that the inputs from the cortex have the capacity directly to excite the relay cells, or indirectly to inhibit them via the RTN, serving to synchronize high- or low-frequency oscillatory activity respectively in the thalamocorticothalamic network. Differences in the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subunit composition of receptors at synapses formed by branches of the same corticothalamic axon in the RTN and dorsal thalamus are an important element in the capacity of the cortex to synchronize low-frequency oscillations in the network. Interactions of focused corticothalamic axons arising from layer VI cortical cells and diffuse corticothalamic axons arising from layer V cortical cells, with the specifically projecting core relay cells and diffusely projecting matrix cells of the dorsal thalamus, form a substrate for synchronization of widespread populations of cortical and thalamic cells during high-frequency oscillations that underlie discrete conscious events.

Nat Neurosci 2003 Jun;6(6):593-9

Synchrony-dependent propagation of firing rate in iteratively constructed networks in vitro.

Reyes AD.

Center for Neural Science, New York University, 4 Washington Place, New York, New York 10003, USA. reyes@cns.nyu.edu

The precise role of synchronous neuronal firing in signal encoding remains unclear. To examine what kinds of signals can be carried by synchrony, I reproduced a multilayer feedforward network of neurons in an in vitro slice preparation of rat cortex using an iterative procedure. When constant and time-varying frequency signals were delivered to the network, the firing of neurons in successive layers became progressively more synchronous. Notably, synchrony in the in vitro network developed even with uncorrelated input, persisted under a wide range of physiological conditions and was crucial for the stable propagation of rate signals. The firing rate was represented by a classical rate code in the initial layers, but switched to a synchrony-based code in the deeper layers.

Neuron 2003 Apr 10;38(1):115-25

Synchrony between Neurons with Similar Muscle Fields in Monkey Motor Cortex.

Jackson A, Gee VJ, Baker SN, Lemon RN.

Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, UCL, WC1N 3BG, London, United Kingdom

Synchronous firing of motor cortex cells exhibiting postspike facilitation (PSF) or suppression (PSS) of hand muscle EMG was examined to investigate the relationship between synchrony and output connectivity. Recordings were made in macaque monkeys performing a precision grip task. Synchronization was assessed with cross-correlation histograms of the activity from 144 pairs of simultaneously recorded neurons, while spike-triggered averages of EMG defined the muscle field for each cell. Cell pairs with similar muscle fields showed greater synchronization than pairs with nonoverlapping fields. Furthermore, cells with opposing effects in the same muscles exhibited negative synchronization. We conclude that synchrony in motor cortex engages networks of neurons directly controlling the same muscle set, while inhibitory connections exist between neuronal populations with opposing output effects.
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Neuropsychopharmacology 2003 May;28(5):857-64

Norepinephrine but not Serotonin Reuptake Inhibitors Enhance Theta and Gamma Activity of the Septo-Hippocampal System.

Hajos M, Hoffmann WE, Robinson DD, Yu JH, Hajos-Korcsok E.

1Neurobiology, Pharmacia Corporation, Kalamazoo, MI, USA.

Current neurobiological concepts attribute a central role of the hippocampal formation in cognitive and affective processes. Recent studies indicate that the hippocampus is affected in human depression, and antidepressant drugs induce hippocampal adaptive changes that are thought to be associated with their therapeutic action. In the present study, we investigated the action of various antidepressant drugs on the activity of the septo-hippocampal system, its oscillatory activity in particular. The acute effects of the norepinephrine (NE) reuptake inhibitors reboxetine and desipramine, and the selective serotonin reuptake inhibitor fluvoxamine were evaluated. Extracellular single-unit recordings were performed from the medial septum/diagonal band of Broca (MS/DBv), with simultaneous hippocampal EEG recordings of anesthetized rats. Systemic administration of reboxetine synchronized hippocampal EEG, resulting in a significant increase in power at theta frequency, and an increase in frequency and power of gamma-wave activity. Parallel to EEG synchrony, reboxetine induced or enhanced theta oscillation of MS/DBv neurons. Oscillatory frequencies of MS/DBv neurons were identical, and phase locked to the corresponding hippocamapal theta frequencies. Under the same experimental conditions, reboxetine induced a two-fold increase in extracellular NE (but not serotonin) levels in the hippocampus as revealed by microdialysis. Desipramine, but not the serotonin reuptake inhibitor fluvoxamine, evoked responses similar to those of reboxetine regarding septo-hippocampal theta activity. The present findings indicate that even though both NE and serotonin reuptake inhibitors are clinically effective antidepressant drugs, their action on the septo-hippocampal oscillatory behavior is different. It is presumed that selective NE reuptake inhibitors could modulate various cognitive processes associated with hippocampal oscillatory activity.Neuropsychopharmacology (2003) 28, 857-864,

Phys Rev Lett 2003 Feb 28;90(8):088101

Synchronization tomography: a method for three-dimensional localization of phase synchronized neuronal populations in the human brain using magnetoencephalography.

Tass PA, Fieseler T, Dammers J, Dolan K, Morosan P, Majtanik M, Boers F, Muren A, Zilles K, Fink GR.

Institute of Medicine, Research Center Julich, 52425 Julich, Germany.

We present a noninvasive technique which allows the anatomical localization of phase synchronized neuronal populations in the human brain with magnetoencephalography. We study phase synchronization between the reconstructed current source density (CSD) of different brain areas as well as between the CSD and muscular activity. We asked four subjects to tap their fingers in synchrony with a rhythmic tone, and to continue tapping at the same rate after the tone was switched off. The phase synchronization behavior of brain areas relevant for movement coordination, inner voice, and time estimation changes drastically when the transition to internal pacing occurs, while their averaged amplitudes remain unchanged. Information of this kind cannot be derived with standard neuroimaging techniques like functional magnetic resonance imaging or positron emission tomography.

Cell Cycle 2003 Jan-Feb;2(1):42-5

Synchrony in human, mouse and bacterial cell cultures a comparison.

Helmstetter CE, Thornton M, Romero A, Eward LK.

Correspondence to: Charles E. Helmstetter; Department of Biological Sciences; Florida Institute of Technology; Melbourne, Florida 32901 USA; Tel.: 321.674.8575; Fax: 321.674.7238.

Growth characteristics of synchronous human MOLT-4, human U-937 and mouse L1210 cultures produced with a new minimally-disturbing technology were compared to each other and to synchronous Escherichia coli B/r. Based on measurements of cell concentrations during synchronous growth, synchrony persisted in similar fashion for all cells. Cell size and DNA distributions in the mammalian cultures also progressed synchronously and reproducibly for multiple cell cycles. The results demonstrate that unambiguous multi-cycle synchrony, critical for verifying the absence of significant growth imbalances induced by the synchronization procedure, is feasible with these cell lines, and possibly others.

J Neurophysiol 2003 Apr 17;

Features of Neuronal Synchrony in Mouse Visual Cortex.

Nase G, Singer W, Monyer H, Engel AK.

Neurophysiologie, Max-Planck-Institut fuer Hirnforschung, Frankfurt, Germany.

Synchronization of neuronal discharges has been hypothesized to play a role in defining cell assemblies representing particular constellations of stimulus features. In many systems and species, synchronization is accompanied by an oscillatory response modulation at frequencies in the gamma-band (>30Hz). The cellular mechanisms underlying these phenomena of synchronization and oscillatory patterning have been studied mainly in vitro due to the difficulty in designing a direct in vivo assay. With the prospect of utilizing conditional genetic manipulations of cortical network components, our objective was to test whether the mouse would meet the criteria to provide a model system for the study of gamma-band synchrony. Multi-unit and local field potential recordings were made from the primary visual cortex of anesthetized C57BL/6J mice. Neuronal responses evoked by moving gratings, bars and random dot patterns were analyzed with respect to neuronal synchrony and temporal patterning. Oscillations at gamma frequencies were readily evoked with all types of stimuli used. Oscillation and synchronization strength were largest for gratings and decreased when the noise level was increased in random-dot patterns. The center peak width of cross-correlograms was smallest for bars and increased with noise, yielding a significant difference between coherent random dot patterns versus patterns with >70% noise. Field potential analysis typically revealed increases of power in the gamma-band during response periods. Our findings are compatible with a role for neuronal synchrony in mediating perceptual binding and suggest the usefulness of the mouse model for testing hypotheses concerning both the mechanisms and the functional role of temporal patterning.

Brain Lang 2003 May;85(2):297-312

Cortical operational synchrony during audio-visual speech integration.

Fingelkurts AA, Fingelkurts AA, Krause CM, Mottonen R, Sams M.

Human Brain Research Group, Human Physiology Department, Moscow State University, 119899, Moscow, Russian Federation

Information from different sensory modalities is processed in different cortical regions. However, our daily perception is based on the overall impression resulting from the integration of information from multiple sensory modalities. At present it is not known how the human brain integrates information from different modalities into a unified percept. Using a robust phenomenon known as the McGurk effect it was shown in the present study that audio-visual synthesis takes place within a distributed and dynamic cortical networks with emergent properties. Various cortical sites within these networks interact with each other by means of so-called operational synchrony (). The temporal synchronization of cortical operations processing unimodal stimuli at different cortical sites reveals the importance of the temporal features of auditory and visual stimuli for audio-visual speech integration.

J Comput Neurosci 2003 May-Jun;14(3):283-309

Dynamics of spiking neurons connected by both inhibitory and electrical coupling.

Lewis TJ, Rinzel J.

Center for Neural Science and Courant Institute for Mathematical Science, New York University, 4 Washington Place, Rm 809, NY 10003, USA. tim.lewis@nyu.edu

We study the dynamics of a pair of intrinsically oscillating leaky integrate-and-fire neurons (identical and noise-free) connected by combinations of electrical and inhibitory coupling. We use the theory of weakly coupled oscillators to examine how synchronization patterns are influenced by cellular properties (intrinsic frequency and the strength of spikes) and coupling parameters (speed of synapses and coupling strengths). We find that, when inhibitory synapses are fast and the electrotonic effect of the suprathreshold portion of the spike is large, increasing the strength of weak electrical coupling promotes synchrony. Conversely, when inhibitory synapses are slow and the electrotonic effect of the suprathreshold portion of the spike is small, increasing the strength of weak electrical coupling promotes antisynchrony (see Fig. 10). Furthermore, our results indicate that, given a fixed total coupling strength, either electrical coupling alone or inhibition alone is better at enhancing neural synchrony than a combination of electrical and inhibitory coupling. We also show that these results extend to moderate coupling strengths.
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J Exp Psychol Hum Percept Perform 2003 Apr;29(2):290-309

Phase attraction in sensorimotor synchronization with auditory sequences: effects of single and periodic distractors on synchronization accuracy.

Repp BH.

Haskins Laboratories, New Haven, Connecticut 06511-6695, USA. repp@haskins.yale.edu

Four experiments showed that both single and periodic distractor tones affected the timing of finger taps produced in synchrony with an isochronous auditory target sequence. Single distractors had only small effects, but periodic distractors occurring at various fixed or changing phase relationships exerted strong phase attraction. The attraction was asymmetric, being stronger when distractors preceded target tones than when they lagged behind. A large pitch difference between target and distractor tones (20 vs. 3 semitones) did not reduce phase attraction substantially, although in the case of continuously changing phase relationships it did prevent complete capture of the taps by the distractors. The results support the hypothesis that phase attraction is an automatic process that is sensitive primarily to event onsets.

Brain Lang 2003 May;85(2):211-21

Neural basis for sentence comprehension deficits in frontotemporal dementia.

Cooke A, DeVita C, Gee J, Alsop D, Detre J, Chen W, Grossman M.

Department of Neurology-2 Gibson, University of Pennsylvania Medical Center, 3400 Spruce Street, 19104-4283, Philadelphia, PA, USA

Many patients with frontotemporal dementia (FTD) have impaired sentence comprehension. However, the pattern of comprehension difficulty appears to vary depending on the clinical subgroup. The purpose of this study was to elucidate the neural basis for these deficits in FTD. We studied patients with two different presentations: Three patients with Progressive Non-Fluent Ahasia (PNFA), and five non-aphasic patients with a dysexecutive and social impairment (EXEC). The FTD patient subgroups were compared to a cohort of 11 healthy seniors with intact sentence comprehension. We monitored regional cerebral activity with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) while subjects read sentences featuring both a grammatically complex object-relative center-embedded clause and a long linkage between the head noun phrase (NP) and the gap where the NP is interpreted in the center-embedded clause. Subjects decided whether the agent of the action is a male or a female. Healthy seniors activated both ventral portions of inferior frontal cortex (vIFC) and dorsal portions of IFC (dIFC) in the left hemisphere, often associated with grammatical and working memory components of these sentences, respectively. PNFA patients differed from healthy controls since they have reduced activation of left vIFC, while EXEC patients have less recruitment of left dIFC. We conclude that FTD subgroups have distinct patterns of sentence comprehension difficulty in part because of selective interruptions of a large-scale neural network for sentence processing.

Brain Res Cogn Brain Res 2003 Jun;17(1):56-67

Shared and dissociated cortical regions for object and letter processing.

Joseph JE, Gathers AD, Piper GA.

Department of Anatomy and Neurobiology, University of Kentucky Medical Center, 800 Rose Street, Davis-Mills Building, Room 308, 40536-0098, Lexington, KY, USA

The present study determined the extent to which object and letter recognition recruit similar or dissociated neural resources. Participants passively viewed and silently named line drawings of objects, single letters, and visual noise patterns and centrally fixated an asterisk. We used whole-brain functional MRI and a very conservative approach to hypothesis testing that distinguished among brain regions that were selectively activated by different experimental conditions and those that were conjointly activated. The left fusiform gyrus (BA 19 & 37) and left inferior frontal cortex BA(44/6) showed a greater degree of conjoined activation for objects and letters than selective activation for either category, whereas left inferior parietal cortex (BA 40) and the left insula showed a strong letter-selective response. Equal recruitment of left fusiform and inferior frontal regions by objects and letters reflects similar demands on cognitive processing by these two categories and argues against category-specific modules in these regions. However, cortical systems for object and letter processing are not completely shared given the exclusive activation of left inferior parietal cortex by letters.

J Neurophysiol 2003 May 15;

Synchrony levels during Evoked Seizure-Like Bursts in Mouse Neocortical Slices.

Van Drongelen W, Koch H, Marcuccilli C, Pena F, Ramirez JM.

Pediatrics, The University of Chicago, Chicago, IL, USA; Neurology, The University of Chicago, Chicago, IL, USA.

Slices (n = 45) from the somatosensory cortex of mouse (P8-13) generate spontaneous bursts of activity (0.10 +/-0.05 Hz) that were recorded extracellularly. Multi-unit action potential (AP) activity was integrated and used as an index of population activity. In this experimental model, seizure-like activity (SLA) was evoked with bicuculline (5-10 micro M) or N-methyl-D-aspartate (NMDA, 5 micro M). SLA was an episode with repetitive bursting at a frequency of 0.50 +/-0.06 Hz. To evaluate whether SLA was associated with a change in synchrony, we obtained simultaneous intracellular and extracellular recordings (n = 40) and quantified the relationship between individual cells and the surrounding population of neurons. During the SLA there was an increase in population activity and bursting activity was observed in neurons and areas that were previously silent. We defined synchrony as cellular activity that is consistently locked with the population bursts. Signal averaging techniques were used to determine this component. To quantitatively assess change in synchronous activity at SLA onset, we estimated the entropy of the single cell spike trains and subdivided this measure into network burst related information and noise-related entropy. The burst related information was not significantly altered at the onset of NMDA evoked SLA and slightly increased when evoked with bicuculline. The signal-to-noise ratio determined from the entropy estimates showed a significant decrease (instead of an expected increase) during SLA. We conclude that the increased population activity during the SLA is due to recruitment of neurons rather than increased synchrony of each of the individual elements.

International Journal of Bifurcation and Chaos, Vol. 10, No. 10 (2000) 2307-2322

CHARACTERISTICS OF THE SYNCHRONIZATION OF BRAIN ACTIVITY IMPOSED BY FINITE CONDUCTION VELOCITIES OF AXONS

WALTER J. FREEMAN
Division of Neurobiology LSA 129, Department of Molecular & Cell Biology, University of California, Berkeley CA 94720-3200, USA
The electrical activity of neurons in brains fluctuates erratically both in terms of pulse trains of single neurons and the dendritic currents of populations of neurons. Obviously the neurons interact with one another in the production of intelligent behavior, so it is reasonable to expect to find evidence for varying degrees of synchronization of their pulse trains and dendritic currents in relation to behavior. However, synaptic communication between neurons depends on propagation of action potentials between neurons, often with appreciable distances between them, and the transmission delays are not compatible with synchronization in any simple way. Evidence is on hand showing that the principal form of synchrony is by establishment of a low degree of covariance among very large numbers of otherwise autonomous neurons, which allows for rapid state transitions of neural populations between successive chaotic basins of attraction along itinerant trajectories. The small fraction of covariant activity is extracted by spatial integration upon axonal transmission over divergent-convergent pathways, through which a remarkable improvement in signal-to-noise ratio is achieved. The raw traces of local activity show little evidence for synchrony, other than zero-lag correlation, which appears to be largely a statistical artifact. Brains rely less on tight phase-locking of small numbers of periodically firing neurons and more on low degrees of cooperativity achieved by order parameters influencing very large numbers of neurons. Brains appear to be indifferent to and undisturbed by widely varying time and phase relations between individual neurons and even large semi-autonomous areas of cortex comprising their mesoscopic neural masses.

Exp Brain Res 2003 May 9;

Ia Afferent input alters the recruitment thresholds and firing rates of single human motor units.

Grande G, Cafarelli E.

Kinesiology and Health Science, Faculty of Pure and Applied Science, York University, Toronto, Canada.

Vibration of the patellar tendon recruits motor units in the knee extensors via excitation of muscle spindles and subsequent Ia afferent input to the alpha-motoneuron pool. Our first purpose was to determine if the recruitment threshold and firing rate of the same motor unit differed when recruited involuntarily via reflex or voluntarily via descending spinal pathways. Although Ia input is excitatory to the alpha-motoneuron pool, it has also been shown paradoxically to inhibit itself. Our second purpose was to determine if vibration of the patellar tendon during a voluntary knee extension causes a change in the firing rate of already recruited motor units. In the first protocol, 10 subjects voluntarily reproduced the same isometric force profile of the knee extensors that was elicited by vibration of the patellar tendon. Single motor unit recordings from the vastus lateralis (VL) were obtained with tungsten microelectrodes and unitary behaviour was examined during both reflex and voluntary knee extensions. Recordings from 135 single motor units showed that both recruitment thresholds and firing rates were lower during reflex contractions. In the second protocol, 7 subjects maintained a voluntary knee extension at 30 N for approximately 40-45 s. Three bursts of patellar tendon vibration were superimposed at regular intervals throughout the contraction and changes in the firing rate of already recruited motor units were examined. A total of 35 motor units were recorded and each burst of superimposed vibration caused a momentary reduction in the firing rates and recruitment of additional units. Our data provide evidence that Ia input modulates the recruitment thresholds and firing rates of motor units providing more flexibility within the neuromuscular system to grade force at low levels of force production.

Exp Brain Res 2003 Jan;148(2):238-46

Processing of temporal information and the basal ganglia: new evidence from fMRI.

Nenadic I, Gaser C, Volz HP, Rammsayer T, Hager F, Sauer H.

Department of Psychiatry, Friedrich-Schiller-University of Jena, Philosophenweg 3, 07740 Jena, Germany, igor.nenadic@uni-jena.de

Temporal information processing is a fundamental brain function, which might include central timekeeping mechanisms independent of sensory modality. Psychopharmacological and patient studies suggest a crucial role of the basal ganglia in time estimation. In this study, functional magnetic resonance imaging (fMRI) was applied in 15 healthy right-handed male subjects performing an auditory time estimation task (duration discrimination of tone pairs in the range of 1,000-1,400 ms) and frequency discriminations (tone pairs differing in pitch, around 1,000 Hz) as an active control task. Task difficulty was constantly modulated by an adaptive algorithm (weighted up-down method) reacting on individual performance. Time estimation (vs rest condition) elicited a distinct pattern of cerebral activity, including the right medial and both left and right dorsolateral prefrontal cortices (DLPFC), thalamus, basal ganglia (caudate nucleus and putamen), left anterior cingulate cortex, and superior temporal auditory areas. Most activations showed lateralisation to the right hemisphere and were similar in the frequency discrimination task. Comparing time and frequency tasks, we isolated activation in the right putamen restricted to time estimation only. This result supports the notion of central processing of temporal information associated with basal ganglia activity. Temporal information processing in the brain might thus be a distributed process of interaction between modality-dependent sensory cortical function, the putamen (with a timing-specific function), and additional prefrontal cortical systems related to attention and memory. Further investigations are needed to delineate the differential contributions of the striatum and other areas to timing.

J Neurophysiol 2003 Jan;89(1):460-71

Modulation of cortical activity during different imitative behaviors.

Koski L, Iacoboni M, Dubeau MC, Woods RP, Mazziotta JC.

Ahmanson-Lovelace Brain Mapping Center, Neuropsychiatric Institute, UCLA School of Medicine, Los Angeles, California 90095.

Imitation is a basic form of motor learning during development. We have a preference to imitate the actions of others as if looking in a mirror (specular imitation: i.e., when the actor moves the left hand, the imitator moves the right hand) rather than with the anatomically congruent hand (anatomic imitation: i.e., actor and imitator both moving the right hand). We hypothesized that this preference reflects changes in activity in previously described frontoparietal cortical areas involved in directly matching observed and executed actions (mirror neuron areas). We used functional magnetic resonance imaging to study brain activity in normal volunteers imitating left and right hand movements with their right hand. Bilateral inferior frontal and right posterior parietal cortex were more active during specular imitation compared with anatomic imitation and control motor tasks. Furthermore this same pattern of activity was also observed in the rostral part of the supplementary motor area (SMA-proper) of the right hemisphere. These findings suggest that the degree of involvement of frontoparietal mirror areas in imitation depends on the nature of the imitative behavior, ruling out a linguistic mediation of these areas in imitation. Moreover, activity in the SMA appears to be tightly coupled to frontoparietal mirror areas when subjects copy the actions of others.

Proc Natl Acad Sci U S A 2003 Feb 4;100(3):1370-4

Contrasting roles of axonal (pyramidal cell) and dendritic (interneuron) electrical coupling in the generation of neuronal network oscillations.

Traub RD, Pais I, Bibbig A, LeBeau FE, Buhl EH, Hormuzdi SG, Monyer H, Whittington MA.

Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Box 31, Brooklyn, NY 11203, USA. roger.traub@downstate.edu

Electrical coupling between pyramidal cell axons, and between interneuron dendrites, have both been described in the hippocampus. What are the functional roles of the two types of coupling? Interneuron gap junctions enhance synchrony of gamma oscillations (25-70 Hz) in isolated interneuron networks and also in networks containing both interneurons and principal cells, as shown in mice with a knockout of the neuronal (primarily interneuronal) connexin36. We have recently shown that pharmacological gap junction blockade abolishes kainate-induced gamma oscillations in connexin36 knockout mice; without such gap junction blockade, gamma oscillations do occur in the knockout mice, albeit at reduced power compared with wild-type mice. As interneuronal dendritic electrical coupling is almost absent in the knockout mice, these pharmacological data indicate a role of axonal electrical coupling in generating the gamma oscillations. We construct a network model of an experimental gamma oscillation, known to be regulated by both types of electrical coupling. In our model, axonal electrical coupling is required for the gamma oscillation to occur at all; interneuron dendritic gap junctions exert a modulatory effect

Nature 2003 Jan 23;421(6921):366-70

Neuronal synchrony does not correlate with motion coherence in cortical area MT.

Thiele A, Stoner G.

Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Natural visual scenes are cluttered with multiple objects whose individual features must somehow be selectively linked (or 'bound') if perception is to coincide with reality. Recent neurophysiological evidence supports a 'binding-by-synchrony' hypothesis: neurons excited by features of the same object fire synchronously, while neurons excited by features of different objects do not. Moving plaid patterns offer a straightforward means to test this idea. By appropriate manipulations of apparent transparency, the component gratings of a plaid pattern can be seen as parts of a single coherently moving surface or as two non-coherently moving surfaces. We examined directional tuning and synchrony of area-MT neurons in awake, fixating primates in response to perceptually coherent and non-coherent plaid patterns. Here we show that directional tuning correlated highly with perceptual coherence, which is consistent with an earlier study. Although we found stimulus-dependent synchrony, coherent plaids elicited significantly less synchrony than did non-coherent plaids. Our data therefore do not support the binding-by-synchrony hypothesis as applied to this class of motion stimuli in area MT.

J Acoust Soc Am 2003 Jan;113(1):462-7

Effect of amplitude modulation coherence for masked speech signals filtered into narrow bands.

Buss E, Wall JW 3rd, Grose JH.

Department of Otolaryngology/Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA. ebuss@med.unc.edu

Introduction of masker amplitude modulation (AM) can improve signal detection in a number of paradigms. In some cases this advantage depends on the coherence of modulation across a relatively wide frequency range. In the experiments described below, observers were asked to identify masked spondee words produced by a single male talker. The target spondees and masking noise were filtered into nine narrow bands, and the coherence of AM of either the speech signal or noise masker was manipulated. Inherent modulation of the masker bands was manipulated via assignment of real and imaginary values to the associated components of each band in the frequency domain, and AM of speech bands was achieved via multiplication with envelopes extracted from these maskers. Responses were based on two alternatives, four alternatives, or open response sets. The effect of masker AM coherence was highly dependent upon the size of the response set: coherent AM was associated with better thresholds in a two-alternative response set, but poorer thresholds in an open response set. Results with AM speech did not depend critically upon the across-frequency temporal synchrony of AM imposed on the speech material.

Hemisphere specialization as an aid in early infancy.

Burnand G.

burn@globalnet.co.uk

In order that different directions of attention can be organized, they have to be labeled and assessed. A statement of a general problem can be regarded as a label for a general direction of attention. Hope about it, as the perceived probability of sufficient success, on the basis of work done, can be regarded as an assessment. It can be argued that a young infant meets an impasse arising from the work on 2 incompatible general problems, (1) that of raising hope of certainty about the environment (linked to the arousal system because repeated stimulation has less effect), and (2) that of raising hope of producing effects (linked to the activation system because here some effect must be produced before activity can cease). A certainty-right hypothesis, that the right hemisphere deals with the certainty problem and the left deals with the producing-effects problem, and hence keeps work on the two problems apart in early infancy while the corpus callosum is undeveloped, and that a matching specialization continues in later life, is supported.
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Hermaphrodite finch hints genes mould brain
Sex chromosomes split personality in bird possessing testis and ovary.
25 March 2003
JOHN WHITFIELD

The half-half finch: male on one side, female on the other

A half-male, half-female bird has added to evidence that genes - not only hormones - underlie the differences between male and female brains.

The cells on the right half of the bird's body contained male sex chromosomes, those on the left, female. The zebra finch had one testis and one ovary; its plumage was bright on its right half, and drab on its left.

It also had a split personality. When ornithologist John Wingfield and his colleagues looked at the bird's brain, they saw that it, too, was divided into male and female sides.

The areas that control singing were bigger on the male side. Male finches court mates with loud and complex songs; females are quieter.

It had been thought that sex differences in the brain were caused by hormones released by the gonads, and were not due to the nerve cells themselves. But both halves of the brain would have received the same chemical signals from the gonads, showing that the different genetic make-up of the brain's two halves must also have had an effect.

The divided bird sang a male's song, and mated a female finch that then laid infertile eggs. The researchers put down the bird when it was almost two years old.

The bizarre zebra finch (Taeniopygia guttata) was born in a lab at Rockefeller University, New York, possibly from a cell containing both male and female chromosomes that was fertilized by two sperm.

Wingfield, who works at the University of Washington, Seattle, was baffled when he first saw the animal - it seemed to change sex before his eyes as it turned. "It was split straight down the middle," he says.

References
Agate, R. J. et al. Neural, not gonadal, origin of brain sex differences in a gynandromorphic finch. Proceedings of the National Academy of Sciences, (2003).

Neuron 2002 Dec 19;36(6):1221-31

The role of medial temporal lobe structures in implicit learning: an event-related FMRI study.

Rose M, Haider H, Weiller C, Buchel C.

Cognitive Neuroscience Laboratory, Department of Neurology, University of Hamburg Medical School, D-20246, Hamburg, Germany. rose@uke.uni-hamburg.de

The medial temporal lobe (MTL) has been associated with declarative learning of flexible relational rules and the basal ganglia with implicit learning of stimulus-response mappings. It remains an open question of whether MTL or basal ganglia are involved when learning flexible relational contingencies without awareness. We studied learning of an explicit stimulus-response association with fMRI. Embedded in this explicit task was a hidden structure that was learnt implicitly. Implicit learning of the sequential regularities of the "hidden rule" activated the ventral perirhinal cortex, within the MTL, whereas learning the fixed stimulus-response associations activated the basal ganglia, indicating that the function of the MTL and the basal ganglia depends on the learned material and not necessarily on the participants' awareness.

Neuroreport 2002 Dec 20;13(18):2475-2481

Alteration of functional neuroanatomy of simple object memory in medial temporal lobe epilepsy patients.

Kang E, Nam H, Lee DS, Lee SK, Lee K, Park SH, Lee JS, Chung JK, Lee MC.

Institute of Radiation Medicine, Seoul National University Medical Research Center Departments of Nuclear Medicine.

Using H O PET, we examined the neuroanatomy associated with a simple form of episodic memory in patients with right or left medial temporal lobe epilepsy and normal healthy controls. When line drawings of common objects were memorized and tested after a 30 min delay, no behavioral difference was found between the patient groups and the controls. However, the patients with epilepsy showed greater cortical activations than the control group on the side ipsilateral to the epileptic focus. rCBF in the anterior thalamic region was enhanced in patients relative to the control group. The results showed that long-term dysfunction of the medial temporal lobe might reinforce alternative memory pathways and recruit a distributed cortical network ipsilateral to their epilepsy focus.(2)

Neuron 2003 Jan 9;37(1):171-80

Recognition memory and the human hippocampus.

Manns JR, Hopkins RO, Reed JM, Kitchener EG, Squire LR.

University of California, San Diego, 92093, La Jolla, CA, USA

The capacity for declarative memory depends on the hippocampal region and adjacent cortex within the medial temporal lobe. One of the most widely studied examples of declarative memory is the capacity to recognize recently encountered material as familiar, but uncertainty remains about whether intact recognition memory depends on the hippocampal region itself and, if so, what the nature of the hippocampal contribution might be. Seven patients with bilateral damage thought to be limited primarily to the hippocampal region were impaired on three standard tests of recognition memory. In addition, the patients were impaired to a similar extent at Remembering and Knowing, measures of the two processes thought to support recognition performance: the ability to remember the learning episode (episodic recollection) and the capacity for judging items as familiar (familiarity).

Rev Neurosci 2002;13(4):299-312

The interaction of rhinal cortex and hippocampus in human declarative memory formation.

Fell J, Klaver P, Elger CE, Fernandez G.

Department of Epileptology, University of Bonn, Bonn, Germany. juergen.fell@ukb.uni-bonn.de

Human declarative memory formation crucially depends on processes within the medial temporal lobe (MTL). These processes can be monitored in real-time by recordings from depth electrodes implanted in the MTL of patients with epilepsy who undergo presurgical evaluation. In our studies, patients performed a word memorization task during depth EEG recording. Afterwards, the difference between event-related potentials (ERPs) corresponding to subsequently remembered versus forgotten words was analyzed. These kind of studies revealed that successful memory encoding is characterized by an early process generated by the rhinal cortex within 300 ms following stimulus onset. This rhinal process precedes a hippocampal process, which starts about 200 ms later. Further investigation revealed that the rhinal process seems to be a correlate of semantic preprocessing which supports memory formation, whereas the hippocampal process appears to be a correlate of an exclusively mnemonic operation. These studies yielded only indirect evidence for an interaction of rhinal cortex and hippocampus. Direct evidence for a memory related cooperation between both structures, however, has been found in a study analyzing so called gamma activity, EEG oscillations of around 40 Hz. This investigation showed that successful as opposed to unsuccessful memory formation is accompanied by an initial enhancement of rhinal-hippocampal phase synchronization, which is followed by a later desynchronization. Present knowledge about the function of phase synchronized gamma activity suggests that this phase coupling and decoupling initiates and later terminates communication between the two MTL structures. Phase synchronized rhinal-hippocampal gamma activity may, moreover, accomplish Hebbian synaptic modifications and thus provide an initial step of declarative memory formation on the synaptic level.

Science 2003 Jan 24;299(5606):577-80

Dynamics of the hippocampus during encoding and retrieval of face-name pairs.

Zeineh MM, Engel SA, Thompson PM, Bookheimer SY.

Ahmanson-Lovelace Brain Mapping Center, UCLA School of Medicine, 660 Charles Young Drive South, Los Angeles, CA 90095-7085, USA.

The medial temporal lobe (MTL) is critical in forming new memories, but how subregions within the MTL carry out encoding and retrieval processes in humans is unknown. Using new high-resolution functional magnetic resonance imaging (fMRI) acquisition and analysis methods, we identified mnemonic properties of different subregions within the hippocampal circuitry as human subjects learned to associate names with faces. The cornu ammonis (CA) fields 2 and 3 and the dentate gyrus were active relative to baseline only during encoding, and this activity decreased as associations were learned. Activity in the subiculum showed the same temporal decline, but primarily during retrieval. Our results demonstrate that subdivisions within the hippocampus make distinct contributions to new memory formation.

J Neurophysiol 2002 Sep;88(3):1433-50

Sound repetition rate in the human auditory pathway: representations in the waveshape and amplitude of fMRI activation.

Harms MP, Melcher JR.

Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston 02114, USA. mharms@epl.meei.harvard.edu

Sound repetition rate plays an important role in stream segregation, temporal pattern recognition, and the perception of successive sounds as either distinct or fused. This study was aimed at elucidating the neural coding of repetition rate and its perceptual correlates. We investigated the representations of rate in the auditory pathway of human listeners using functional magnetic resonance imaging (fMRI), an indicator of population neural activity. Stimuli were trains of noise bursts presented at rates ranging from low (1-2/s; each burst is perceptually distinct) to high (35/s; individual bursts are not distinguishable). There was a systematic change in the form of fMRI response rate-dependencies from midbrain to thalamus to cortex. In the inferior colliculus, response amplitude increased with increasing rate while response waveshape remained unchanged and sustained. In the medial geniculate body, increasing rate produced an increase in amplitude and a moderate change in waveshape at higher rates (from sustained to one showing a moderate peak just after train onset). In auditory cortex (Heschl's gyrus and the superior temporal gyrus), amplitude changed somewhat with rate, but a far more striking change occurred in response waveshape-low rates elicited a sustained response, whereas high rates elicited an unusual phasic response that included prominent peaks just after train onset and offset. The shift in cortical response waveshape from sustained to phasic with increasing rate corresponds to a perceptual shift from individually resolved bursts to fused bursts forming a continuous (but modulated) percept. Thus at high rates, a train forms a single perceptual "event," the onset and offset of which are delimited by the on and off peaks of phasic cortical responses. While auditory cortex showed a clear, qualitative correlation between perception and response waveshape, the medial geniculate body showed less correlation (since there was less change in waveshape with rate), and the inferior colliculus showed no correlation at all. Overall, our results suggest a population neural representation of the beginning and the end of distinct perceptual events that is weak or absent in the inferior colliculus, begins to emerge in the medial geniculate body, and is robust in auditory cortex.

Am J Psychiatry 2002 Nov;159(11):1830-40

Unmasking disease-specific cerebral blood flow abnormalities: mood challenge in patients with remitted unipolar depression.

Liotti M, Mayberg HS, McGinnis S, Brannan SL, Jerabek P.

OBJECTIVE: Remitted major depressive disorder is a vulnerable clinical state, suggesting persistence of an underlying disease diathesis between episodes. To investigate neural correlates of such risk and to identify potential depression trait markers, euthymic unipolar patients in remission, acutely depressed patients, and never-depressed volunteers were studied before and after transient sad mood challenge. METHOD: Common and differential changes in regional blood flow among the groups relative to the baseline state were examined with [(15)O]H(2)O positron emission tomography after provocation of sadness with autobiographical memory scripts. RESULTS: Mood provocation in both depressed groups resulted in regional cerebral blood flow (rCBF) decreases in medial orbitofrontal cortex Brodmann's area 10/11, which were absent in the healthy group. In the remitted group, mood provocation produced a unique rCBF decrease in pregenual anterior cingulate 24a. The main effects in healthy subjects, an rCBF increase in subgenual cingulate Brodmann's area 25 and a decrease in right prefrontal cortex Brodmann's area 9, were not present in the depressed groups. CONCLUSIONS: Mood challenge in unipolar euthymic patients in full remission unmasks an apparent depression trait marker. The pattern of acute CBF changes is distinct from that seen in euthymic healthy volunteers and mirrors the untreated depressed state seen during a major depressive episode and the pattern of change seen in depressed patients. These findings suggest that disease-specific modifications of pathways mediating transient mood changes are present in unipolar depression independent of clinical illness status. These findings have implications for understanding the vulnerability of remitted patients for illness relapse.

==========================

Musical syntax is processed in Broca's area: an MEG study.
Maess B, Koelsch S, Gunter TC, Friederici AD
Nat Neurosci 2001 May 4:540-5

Abstract
The present experiment was designed to localize the neural substrates that process music-syntactic incongruities, using magnetoencephalography (MEG). Electrically, such processing has been proposed to be indicated by early right-anterior negativity (ERAN), which is elicited by harmonically inappropriate chords occurring within a major-minor tonal context. In the present experiment, such chords elicited an early effect, taken as the magnetic equivalent of the ERAN (termed mERAN). The source of mERAN activity was localized in Broca's area and its right-hemisphere homologue, areas involved in syntactic analysis during auditory language comprehension. We find that these areas are also responsible for an analysis of incoming harmonic sequences, indicating that these regions process syntactic information that is less language-specific than previously believed.

Curr Biol 2000 Apr 6;10(7):383-92

Interhemispheric switching mediates perceptual rivalry.

Miller SM, Liu GB, Ngo TT, Hooper G, Riek S, Carson RG, Pettigrew JD.

Vision, Touch and Hearing Research Centre, Department of Physiology and Pharmacology, The University of Queensland, Brisbane, 4072, Australia. s.miller@vthrc.uq.edu.au

BACKGROUND: Binocular rivalry refers to the alternating perceptual states that occur when the images seen by the two eyes are too different to be fused into a single percept. Logothetis and colleagues have challenged suggestions that this phenomenon occurs early in the visual pathway. They have shown that, in alert monkeys, neurons in the primary visual cortex continue to respond to their preferred stimulus despite the monkey reporting its absence. Moreover, they found that neural activity higher in the visual pathway is highly correlated with the monkey's reported percept. These and other findings suggest that the neural substrate of binocular rivalry must involve high levels, perhaps the same levels involved in reversible figure alternations. RESULTS: We present evidence that activation or disruption of a single hemisphere in human subjects affects the perceptual alternations of binocular rivalry. Unilateral caloric vestibular stimulation changed the ratio of time spent in each competing perceptual state. Transcranial magnetic stimulation applied to one hemisphere disrupted normal perceptual alternations when the stimulation was timed to occur at one phase of the perceptual switch, but not at the other. Furthermore, activation of a single hemisphere by caloric stimulation affected the perceptual alternations of a reversible figure, the Necker cube. CONCLUSIONS: Our findings suggest that interhemispheric switching mediates perceptual rivalry. Thus, competition for awareness in both binocular rivalry and reversible figures occurs between, rather than within, each hemisphere. This interhemispheric switch hypothesis has implications for understanding the neural mechanisms of conscious experience and also has clinical relevance as the rate of both types of perceptual rivalry is slow in bipolar disorder (manic depression).

PNAS | June 10, 2003 | vol. 100 | no. 12 | 7406-7411

Psychology
Mapping the genetic variation of executive attention onto brain activity

Jin Fan , John Fossella , Tobias Sommer , Yanghong Wu and Michael I. Posner ¶ ||

Sackler Institute for Developmental Psychobiology, Weill Medical College of Cornell University, New York, NY 10021; Department of Neurology, University of Hamburg, 20246 Hamburg, Germany; Department of Psychology, Beijing University, Beijing 100871, China; and ¶Department of Psychology, University of Oregon, Eugene, OR 97403

Contributed by Michael I. Posner, April 9, 2003

Brain imaging data have repeatedly shown that the anterior cingulate cortex is an important node in the brain network mediating conflict. We previously reported that polymorphisms in dopamine receptor (DRD4) and monoamine oxidase A (MAOA) genes showed significant associations with efficiency of handling conflict as measured by reaction time differences in the Attention Network Test (ANT). To examine whether this genetic variation might contribute to differences in brain activation within the anterior cingulate cortex, we genotyped 16 subjects for the DRD4 and MAOA genes who had been scanned during the ANT. In each of the two genes previously associated with more efficient handling of conflict in reaction time experiments, we found a polymorphism in which persons with the allele associated with better behavioral performance showed significantly more activation in the anterior cingulate while performing the ANT than those with the allele associated with worse performance. The results demonstrate how genetic differences among individuals can be linked to individual differences in neuromodulators and in the efficiency of the operation of an appropriate attentional network.

Proc R Soc Lond B Biol Sci 1998 Nov 22;265(1411):2141-8

A 'sticky' interhemispheric switch in bipolar disorder?

Pettigrew JD, Miller SM.

Vision, Touch and Hearing Research Centre, University of Queensland, St Lucia, Brisbane, Australia. j.pettigrew@vthrc.uq.edu.au

Despite years of research into bipolar disorder (manic depression), its underlying pathophysiology remains elusive. It is widely acknowledged that the disorder is strongly heritable, but the genetics are complex with less than full concordance in monozygotic twins and at least four susceptibility loci identified. We propose that bipolar disorder is the result of a genetic propensity for slow interhemispheric switching mechanisms that become 'stuck' in one or the other state. Because slow switches are also 'sticky' when compared with fast switches, the clinical manifestations of bipolar disorder may be explained by hemispheric activation being 'stuck' on the left (mania) or on the right (depression). Support for this 'sticky' interhemispheric switching hypothesis stems from our recent observation that the rate of perceptual alternation in binocular rivalry is slow in euthymic subjects with bipolar disorder (n = 18, median = 0.27 Hz) compared with normal controls (n = 49, median = 0.60 Hz, p < 0.0005). We have presented evidence elsewhere that binocular rivalry is itself an interhemispheric switching phenomenon. The rivalry alternation rate (putative interhemispheric switch rate) is robust in a given individual, with a test-retest correlation of more than 0.8, making it suitable for genetic studies. The interhemispheric switch rate may provide a trait-dependent biological marker for bipolar disorder.

Adv Exp Med Biol 2002;508:461-9

Vision as motivation: interhemispheric oscillation alters perception.

Pettigrew JD, Carter O.

Vision Touch and Hearing Research Centre, School of Biomedical Sciences, University of Queensland, Australia. j.pettigrew@vthrc.uq.edu.au

The well-recognised proclivity of primates for things visual can sometimes mislead us into thinking that a high order visual process is taking place at a much earlier level of processing than it is. We illustrate this with a new illusion, Bonneh's "motion-induced-blindness", that involves the intermittent disappearance and reappearance of simple bright targets under the influence of a moving background. This perceptual oscillation is strongly affected by the mood and impulsivity of the subject, in line with other evidence that this simple disappearance and reappearance must be taking place at a high level of processing, perhaps at the level of the cerebral hemsipheres themselves.

Brain Res 1999 Mar 13;821(2):383-91

Relations of hippocampal volume and dentate gyrus width to gonadal hormone levels in male and female meadow voles.

Galea LA, Perrot-Sinal TS, Kavaliers M, Ossenkopp KP.

Department of Psychology, University of British Columbia, 2136 West Mall, Vancouver, BC, Canada. lgalea@psych.ubc.ca

The present study examined hippocampal volume and dentate gyrus width and their relations to gonadal hormone levels in adult male and female meadow voles, Microtus pennsylvanicus. Females were split into High and Low Estradiol groups based on the median estradiol level. Males were similarly split into High and Low Testosterone groups. Contrary to previous reports in wild meadow voles, there was no evidence of an overall sex difference in hippocampal volume. However, when male-female comparisons were limited to High Testosterone males and Low Estradiol females a significant sex difference in hippocampal volume favouring males did emerge. Hippocampal volume in males was related to testosterone level, with High Testosterone males having significantly larger hippocampi than Low Testosterone males. Similarly, there was a significant influence of plasma estradiol level on hippocampal volume and left dentate gyrus width, with High Estradiol females having larger hippocampi and dentate gyrus width than Low Estradiol females. In addition, consistent with previous findings in the laboratory rat, there were sex differences favouring males in right dentate gyrus width. These findings show that there is a complex relationship between hippocampal volume, dentate gyrus width and gonadal hormone levels in male and female meadow voles.

Am J Physiol 1997 Nov;273(5 Pt 2):R1683-9

Amygdala but not hippocampal lesions impair olfactory memory for mate in prairie voles (Microtus ochrogaster).

Demas GE, Williams JM, Nelson RJ.

Department of Psychology, Johns Hopkins University, Baltimore, Maryland 21218, USA.

Exposure to an unfamiliar male conspecific results in pregnancy interruption (i.e., the Bruce effect) in rodents. Unlike most laboratory rodents, female prairie voles (Microtus ochrogaster) are induced into estrus by chemosensory stimuli contained in the urine of male conspecifics while grooming the anogenital (A-G) region of unfamiliar males. Female prairie voles maintain a brief "memory" for the stud male for 8-10 days after mating. Subsequent exposure to the same mate within this 8- to 10-day window does not elicit A-G investigation by the female and pregnancy block does not result. However, exposure to the original male after 10 days evokes A-G investigation and pregnancy block. To determine the neuroanatomic area(s) involved in olfactory memory for mate, female voles received bilateral electrolytic lesions of either the amygdala or hippocampus. Females were subsequently exposed to males for 48 h, separated for 3 days, then reintroduced to their original mate for 24 h. Although pregnancy rate did not differ among the experimental groups, a greater proportion of amygdala-lesioned females displayed pregnancy block when reexposed to their previous mates compared with hippocampal- or sham-lesioned voles. Amygdala-lesioned voles also displayed a greater number of A-G investigations compared with the other groups. Performance on olfactory tests was not impaired. Taken together, these results suggest that the amygdala plays an important role in olfactory memory for mate in prairie voles.

(IDM : link this to the reference to empathy and smell associated with the amygdala)

Proc Natl Acad Sci U S A 1990 Aug;87(16):6349-52

Evolution of spatial cognition: sex-specific patterns of spatial behavior predict hippocampal size.

Jacobs LF, Gaulin SJ, Sherry DF, Hoffman GE.

Department of Anthropology, University of Pittsburgh, PA 15260.

In a study of two congeneric rodent species, sex differences in hippocampal size were predicted by sex-specific patterns of spatial cognition. Hippocampal size is known to correlate positively with maze performance in laboratory mouse strains and with selective pressure for spatial memory among passerine bird species. In polygamous vole species (Rodentia: Microtus), males range more widely than females in the field and perform better on laboratory measures of spatial ability; both of these differences are absent in monogamous vole species. Ten females and males were taken from natural populations of two vole species, the polygamous meadow vole, M. pennsylvanicus, and the monogamous pine vole, M. pinetorum. Only in the polygamous species do males have larger hippocampi relative to the entire brain than do females. Two-way analysis of variance shows that the ratio of hippocampal volume to brain volume is differently related to sex in these two species. To our knowledge, no previous studies of hippocampal size have linked both evolutionary and psychometric data to hippocampal dimensions. Our controlled comparison suggests that evolution can produce adaptive sex differences in behavior and its neural substrate.

Proc Natl Acad Sci U S A 2001 Jun 5;98(12):6941-4

A larger hippocampus is associated with longer-lasting spatial memory.

Biegler R, McGregor A, Krebs JR, Healy SD.

Institute of Cell, Animal, and Population Biology, King's Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland, United Kingdom.

Volumetric studies in a range of animals (London taxi-drivers, polygynous male voles, nest-parasitic female cowbirds, and a number of food-storing birds) have shown that the size of the hippocampus, a brain region essential to learning and memory, is correlated with tasks involving an extra demand for spatial learning and memory. In this paper, we report the quantitative advantage that food storers gain from such an enlargement. Coal tits (Parus ater) a food-storing species, performed better than great tits (Parus major), a nonstoring species, on a task that assessed memory persistence but not on a task that assessed memory resolution or on one that tested memory capacity. These results show that the advantage to the food-storing species associated with an enlarged hippocampus is one of memory persistence.

Proc Natl Acad Sci U S A 2000 Apr 11;97(8):4398-403

Navigation-related structural change in the hippocampi of taxi drivers.

Maguire EA, Gadian DG, Johnsrude IS, Good CD, Ashburner J, Frackowiak RS, Frith CD.

Wellcome Department of Cognitive Neurology, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom. e.maguire@fil.ion.ucl.ac.uk

Structural MRIs of the brains of humans with extensive navigation experience, licensed London taxi drivers, were analyzed and compared with those of control subjects who did not drive taxis. The posterior hippocampi of taxi drivers were significantly larger relative to those of control subjects. A more anterior hippocampal region was larger in control subjects than in taxi drivers. Hippocampal volume correlated with the amount of time spent as a taxi driver (positively in the posterior and negatively in the anterior hippocampus). These data are in accordance with the idea that the posterior hippocampus stores a spatial representation of the environment and can expand regionally to accommodate elaboration of this representation in people with a high dependence on navigational skills. It seems that there is a capacity for local plastic change in the structure of the healthy adult human brain in response to environmental demands.

J Neurosci 2002 Nov 15;22(22):10009-17

Vestibular information is required for dead reckoning in the rat.

Wallace DG, Hines DJ, Pellis SM, Whishaw IQ.

Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada T1K 3M4.

Dead reckoning is an on-line form of spatial navigation used by an animal to identify its present location and return directly to a starting location, even after circuitous outward trips. At present, it is not known which of several self-movement cues (efferent copy from movement commands, proprioceptive information, sensory flow, or vestibular information) are used to compute homeward trajectories. To determine whether vestibular information is important for dead reckoning, the impact of chemical labyrinthectomy was evaluated in a test that demanded on-line computation of a homeward trajectory. Rats were habituated to leave a refuge that was visible from all locations on a circular table to forage for large food pellets, which they carried back to the refuge to eat. Two different probe trials were given: (1) the rats foraged from the same spatial location from a hidden refuge in the light and so were able to use visual cues to navigate; (2) the same procedure took place in the dark, constraining the animals to dead reckon. Although control rats carried food directly and rapidly back to the refuge on both probes, the rats with vestibular lesions were able to do so on the hidden refuge but not on the dark probe. The scores of vestibular reflex tests predicted the dead reckoning deficit. The vestibular animals were also impaired in learning a new piloting task. This is the first unambiguous demonstration that vestibular information is used in dead reckoning and also contributes to piloting.

Behav Brain Res 2002 Oct 17;136(1):201

Bilateral participation of the hippocampus in familiar landmark navigation by homing pigeons.

Gagliardo A, Odetti F, Ioale P, Bingman VP, Tuttle S, Vallortigara G.

Dipartimento di Etologia, Ecologia ed Evoluzione, Universita di Pisa, Via A.Volta 6, I-56126, Pisa, Italy

Recent findings indicate a different role of the left and right hippocampal formation (RHF) in homing pigeon navigational map learning. However, it remains uncertain whether the left or the RHF may play a more important role in navigation based on familiar landmarks. In the present study, we attempted to answer this question by experimentally releasing control and left and right hippocampal ablated pigeons from familiar training sites under anosmia, to render their navigational map dysfunctional, and after a phase-shift of the light-dark cycle, to place into conflict a pilotage-like landmark navigational strategy and a site-specific compass orientation landmark navigational strategy. Both left and right hippocampal ablated birds succeeded in learning to navigate by familiar landmarks, and both preferentially relied on sun-compass based, site-specific compass orientation to home. Like bilateral hippocampal lesioned birds, and in contrast to intact controls, neither ablation group adopted a pilotage-like strategy. We conclude that both the left and RHF are necessary if pilotage-like, familiar landmark navigation is to be learned or preferentially used for navigation.

J Neurosci 1996 Dec 15;16(24):8027-40

Dynamics of mismatch correction in the hippocampal ensemble code for space: interaction between path integration and environmental cues.

Gothard KM, Skaggs WE, McNaughton BL.

Arizona Research Laboratories Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, Arizona 85724, USA.

Populations of hippocampal neurons were recorded simultaneously in rats shuttling on a track between a fixed reward site at one end and a movable reward site, mounted in a sliding box, at the opposite end. While the rat ran toward the fixed site, the box was moved. The rat returned to the box in its new position. On the initial part of all journeys, cells fired at fixed distances from the origin, whereas on the final part, cells fired at fixed distances from the destination. Thus, on outward journeys from the box, with the box behind the rat, the position representation must have been updated by path integration. Farther along the journey, the place field map became aligned on the basis of external stimuli. The spatial representation was quantified in terms of population vectors. During shortened journeys, the vector shifted from an alignment with the origin to an alignment with the destination. The dynamics depended on the degree of mismatch with respect to the full-length journey. For small mismatches, the vector moved smoothly through intervening coordinates until the mismatch was corrected. For large mismatches, it jumped abruptly to the new coordinate. Thus, when mismatches occur, path integration and external cues interact competitively to control place-cell firing. When the same box was used in a different environment, it controlled the alignment of a different set of place cells. These data suggest that although map alignment can be controlled by landmarks, hippocampal neurons do not explicitly represent objects or events.

Nature 1998 Nov 5;396(6706):75-7

Hippocampal lesions disrupt navigation based on cognitive maps but not heading vectors.

Pearce JM, Roberts AD, Good M.

School of Psychology, Cardiff University, UK. pearcejm@cardiff.ac.uk

Animals can find a hidden goal in several ways. They might use a cognitive map that encodes information about the geometric relationship between the goal and two or more landmarks. Alternatively, they might use a heading vector that specifies the direction and distance of the goal from a single landmark. Rats with damage to the hippocampus have difficulty in finding a hidden goal. Here we determine which of the above strategies is affected by such damage. Rats were required to swim in a water maze to a submerged platform, which was always at the same distance and direction from a landmark. The platform and landmark remained in the same place for the four trials of each session, but they were moved to a new position at the start of a session. Rats with damage to the hippocampus found the platform more efficiently than did normal rats in the first trial of a session but, in contrast to normal rats, their performance did not improve during a session. Our results indicate that hippocampally damaged rats are able to navigate by means of heading vectors but not cognitive maps.

Learn Mem 2001 Nov-Dec;8(6):326-35

Verbal and nonverbal emotional memory following unilateral amygdala damage.

Buchanan TW, Denburg NL, Tranel D, Adolphs R.

Department of Neurology, Division of Cognitive Neuroscience, University of Iowa, College of Medicine, Iowa City, Iowa 52242, USA. tony-buchanan@uiowa.edu

The amygdala is involved in the normal facilitation of memory by emotion, but the separate contributions of the left and right amygdala to memory for verbal or nonverbal emotional material have not been investigated. Fourteen patients with damage to the medial temporal lobe including the amygdala (seven left, seven right), 18 brain-damaged, and 36 normal controls were exposed to emotional and neutral pictures accompanied by verbal narratives. Memory for both narratives and pictures was assessed with a free recall test 24 h later. Subjects with left amygdala damage failed to show the normally robust enhancement of memory for verbal and nonverbal emotional stimuli. The group with right amygdala damage showed the normal pattern of facilitation of memory by emotion for both verbal and nonverbal stimuli despite an overall reduction in memory performance. Furthermore, subjects with left amygdala damage were disproportionately impaired on memory for emotional narratives as compared with memory for emotional pictures. The latter finding offers partial support for a lateralized and material-specific pattern of the amygdala's contribution to emotional memory

Eur J Pharmacol 2002 Jan 18;435(1):59-65

Enhancement of delayed release of dopamine in the amygdala induced by conditioned fear stress in methamphetamine-sensitized rats.

Suzuki T, Ishigooka J, Watanabe S, Miyaoka H.

Department of Psychiatry, Kitasato University School of Medicine 2-1-1 Asamizodai, Kanagawa 228-8520, Sagamihara, Japan.

Behavior during conditioned fear stress, a form of psychological stress, and the release of dopamine in the amygdala were measured over time using methamphetamine-sensitized rats, which are considered to be a model of hypersensitivity and vulnerability to emotional stress associated with stimulant-induced psychosis and schizophrenia. Dopamine release in the amygdala showed a delayed increase following completion of freezing behavior induced by conditioned fear stress regardless of the presence or absence of methamphetamine-sensitization. Since methamphetamine treatment did not lower the basal level of dopamine in the amygdala, under the conditions of this study, methamphetamine was presumed not to show neurotoxicity. On the other hand, basal dopamine levels after 15 h of repeated electric foot shock were about 40% lower than those in the control group (p<0.0002). In addition, dopamine release following conditioned fear stress in animals repeatedly treated with methamphetamine increased significantly from 40 to 100 min after conditioned fear stress while the duration of freezing behavior or latency of the appearance of grooming were not different from those in the control group. The above results suggested that delayed dopamine release in the amygdala is a phenomenon strongly associated with the emotional context of conditioned fear stress, and hypersensitivity and vulnerability to stress are at least partially involved with the overreaction to stress.

Memory 2002 Mar;10(2):99-111

Is flashbulb memory a special instance of source memory? Evidence from older adults.

Davidson PS, Glisky EL.

Department of Psychology, University of Arizona, Tucson 85721-0068, USA. pdavidso@u.arizona.edu

Flashbulb memories (FMs) are vivid, stable memories for the reception of arousing, consequential news. Although such memories have been found in people of all ages, in the only examination of age differences to date, Cohen, Conway, and Maylor (1994) reported that older adults were less likely than young adults to experience a FM. We hypothesised that FM would be impaired in older adults with reduced frontal lobe (FL) function. To test this hypothesis, we asked older adults, who had been characterised according to FL function, to recall details of the moment that they first heard the news about the deaths of Princess Diana and Mother Teresa. Long-term retention was tested 6 months later. Details concerning the reception of the news about Princess Diana's death were retained better than those associated with Mother Teresa's death. Importantly, there was no evidence that memory for these contextual details was related to FL function. A measure of medial temporal lobe function, derived from neuropsychological tests of episodic memory, was also not associated with memory for the reception events, although it was associated with memory for the details of an everyday autobiographical event. We speculated that emotionally arousing autobiographical memories may be qualitatively different from everyday memories and may involve the amygdala.

Respir Physiol 2001 Nov 1;128(2):171-7

The effect of anticipatory anxiety on breathing and metabolism in humans.

Masaoka Y, Homma I.

Second Department of Physiology, Showa University School of Medicine, Hatanodai 1-5-8, Shinagawa-ku, 142-8555, Tokyo, Japan.

Respiratory patterns are influenced by cortical and limbic factors and generated by a complex interaction between metabolic requirements and their behavioral effects. Our previous results showed that the temporal pole and the amygdala in the limbic system are related to anxiety and associated with an increase of respiratory frequency, especially in high trait anxiety subjects. The purpose of this study was to investigate the relationship between respiratory patterns and metabolic output during the production of anticipatory anxiety. In all subjects, fR increased without changes in V(O(2)), V(CO(2)) and HR; and PET(CO(2)) decreased during anticipatory anxiety. In the subjects with high trait anxiety, the increase of fR and the decrease of TE were larger than those in the subjects with low trait anxiety. These results suggest that an increase in respiratory frequency is not related to metabolic factors and is consistent with a mechanism involving the limbic system modulating respiratory drive.

Nat Rev Neurosci 2002 Feb;3(2):122-31

Parallels between cerebellum- and amygdala-dependent conditioning.

Medina JF, Christopher Repa J, Mauk MD, LeDoux JE.

Howard Hughes Medical Institute, Department of Physiology, W.M. Keck Foundation Center for Integrative Neurobiology, University of California, 513 Parnassus Avenue, Room HSE-808, San Francisco, California 94143-0444, USA. jmedina@phy.ucsf.edu

Recent evidence from cerebellum-dependent motor learning and amygdala-dependent fear conditioning indicates that, despite being mediated by different brain systems, these forms of learning might use a similar sequence of events to form new memories. In each case, learning seems to induce changes in two different groups of neurons. Changes in the first class of cells are induced very rapidly during the initial stages of learning, whereas changes in the second class of cells develop more slowly and are resistant to extinction. So, anatomically distinct cell populations might contribute differentially to the initial encoding and the long-term storage of memory in these two systems.

Neurobiol Learn Mem 2002 Mar;77(2):250-75

Conditioned memory modulation, freezing, and avoidance as measures of amygdala-mediated conditioned fear.

Holahan MR, White NM.

Department of Psychology, McGill University, Montreal, Quebec, Canada H3A 1B1. mholahan@ego.psych.mcgill.ca

Three conditioned aversive responses were used to infer the existence of an unobservable central state of "conditioned fear," and the roles of certain amygdala subregions in producing these responses were investigated. Rats received tone-shock pairings in one compartment of a shuttle box and no tones or shocks in the other, distinctive, compartment. They were then trained to find food in one arm of a Y-maze. After the final training trial they were exposed to different sets of stimuli in the shuttle box with no shock. Twenty-four hours later rats that had received immediate posttraining exposure to the conditioned stimuli (in the shock-paired compartment) made significantly more correct responses on the Y-maze than rats that had been exposed to the neutral stimuli (in the no-shock compartment) or rats that had received delayed posttraining exposure to the conditioned stimuli. This constitutes a demonstration of posttraining memory modulation by conditioned aversive stimuli. Freezing increased during posttraining exposure to the conditioned stimuli compared to the neutral stimuli. When subsequently allowed to move freely between the two compartments, the rats in all groups also showed significant conditioned avoidance of the compartment containing the conditioned stimuli. In a second experiment the effects of lesions confined to specific parts of the amygdala on the three conditioned responses (memory modulation, freezing, avoidance) were tested. Lesions of the central nucleus impaired all three conditioned responses; lesions of the medial nucleus impaired conditioned modulation and avoidance. These lesions had no effect on freezing during the training trials. Lesions of the lateral and basolateral nuclei attenuated freezing during both training and testing. The findings suggest that the central and medial nuclei of the amygdala may be important parts of neural circuits mediating conditioned responses that constitute conditioned aversive states, but that conditioned freezing may be mediated independently.

Neuron 2002 Mar 14;33(6):983-94

The role of the amygdala in signaling prospective outcome of choice.

Kahn I, Yeshurun Y, Rotshtein P, Fried I, Ben-Bashat D, Hendler T.

Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 64239, Tel Aviv, Israel.

Can brain activity reveal a covert choice? Making a choice often evokes distinct emotions that accompany decision processes. Amygdala has been implicated in choice behavior that is guided by a prospective negative outcome. However, its specific involvement in emotional versus cognitive processing of choice behavior has been a subject of controversy. In this study, the human amygdala was monitored by functional magnetic resonance imaging (fMRI) while subjects were playing in a naturalistic choice paradigm against the experimenter. In order to win, players had to occasionally choose to bluff their opponent, risk "getting caught," and suffer a loss. A critical period, when choice has been made but outcome was still unknown, activated the amygdala preferentially following the choice that entailed risk of loss. Thus, the response of the amygdala differentiated between subject's covert choice of either playing fair or foul. These results support a role of the amygdala in choice behavior, both in the appraisal of inherent value of choice and the signaling of prospective negative outcomes.

J Neurosci 2002 Apr 1;22(7):2730-6

The neural correlates of moral sensitivity: a functional magnetic resonance imaging investigation of basic and moral emotions.

Moll J, de Oliveira-Souza R, Eslinger PJ, Bramati IE, Mourao-Miranda J, Andreiuolo PA, Pessoa L.

Neuroimaging and Behavioral Neurology Group, Hospitais D'Or and LABS, RJ, 22281-081, Brazil. jmoll@neuroimage.com

Humans are endowed with a natural sense of fairness that permeates social perceptions and interactions. This moral stance is so ubiquitous that we may not notice it as a fundamental component of daily decision making and in the workings of many legal, political, and social systems. Emotion plays a pivotal role in moral experience by assigning human values to events, objects, and actions. Although the brain correlates of basic emotions have been explored, the neural organization of "moral emotions" in the human brain remains poorly understood. Using functional magnetic resonance imaging and a passive visual task, we show that both basic and moral emotions activate the amygdala, thalamus, and upper midbrain. The orbital and medial prefrontal cortex and the superior temporal sulcus are also recruited by viewing scenes evocative of moral emotions. Our results indicate that the orbital and medial sectors of the prefrontal cortex and the superior temporal sulcus region, which are critical regions for social behavior and perception, play a central role in moral appraisals. We suggest that the automatic tagging of ordinary social events with moral values may be an important mechanism for implicit social behaviors in humans.

Neuroreport 2002 Jan 21;13(1):15-9

Positive and negative emotional verbal stimuli elicit activity in the left amygdala.

Hamann S, Mao H.

Department of Psychology, Emory University, Atlanta, GA 30322, USA.

The human amygdala's involvement in negative emotion is well established, but relatively little is known regarding its role in positive emotion. Here we examined the neural response to emotionally positive, negative, and neutral words using fMRI. Relative to neutral words, positive and negative emotional words elicited greater activity in the left amygdala. Positive but not negative words elicited activity in dorsal and ventral striatal regions which have been linked in previous neuroimaging studies to reward and positive affect, including caudate, putamen, globus pallidus, and accumbens. These findings provide the first direct evidence that the amygdala is involved in emotional reactions elicited by both positive and negative emotional words, and further indicate that positive words additionally activate brain regions related to reward.

Psychol Sci 2002 Mar;13(2):135-41

Ecstasy and agony: activation of the human amygdala in positive and negative emotion.

Hamann SB, Ely TD, Hoffman JM, Kilts CD.

Department of Psychology, Emory University, Atlanta, GA 30322, USA. shamann@emory.edu

Considerable evidence indicates that the amygdala plays a critical role in negative, aversive human emotions. Although researchers have speculated that the amygdala plays a role in positive emotion, little relevant evidence exists. We examined the neural correlates of positive and negative emotion using positron emission tomography (PET), focusing on the amygdala. Participants viewed positive and negative photographs, as well as interesting and uninteresting neutral photographs, during PET scanning. The left amygdala and ventromedial prefrontal cortex were activated during positive emotion, and bilateral amygdala activation occurred during negative emotion. High-interest, unusual photographs also elicited left-amygdala activation, a finding consistent with suggestions that the amygdala is involved in vigilance reactions to associatively ambiguous stimuli. The current results constitute the first neuroimaging evidence for a role of the amygdala in positive emotional reactions elicited by visual stimuli. Although the amygdala appears to play a more extensive role in negative emotion, it is involved in positive emotion as well.

: Nat Rev Neurosci 2002 Jul;3(7):563-73

The amygdala and reward.

Baxter MG, Murray EA.

Department of Psychology, Harvard University, 906 William James Hall, 33 Kirkland Street, Cambridge, Massachusetts 02138, USA. mbaxter@wjh.harvard.edu

The amygdala -- an almond-shaped group of nuclei at the heart of the telencephalon -- has been associated with a range of cognitive functions, including emotion, learning, memory, attention and perception. Most current views of amygdala function emphasize its role in negative emotions, such as fear, and in linking negative emotions with other aspects of cognition, such as learning and memory. However, recent evidence supports a role for the amygdala in processing positive emotions as well as negative ones, including learning about the beneficial biological value of stimuli. Indeed, the amygdala's role in stimulus-reward learning might be just as important as its role in processing negative affect and fear conditioning.

Proc Natl Acad Sci U S A 2002 Aug 6;99(16):10789-94

Sex differences in the neural basis of emotional memories.

Canli T, Desmond JE, Zhao Z, Gabrieli JD.

Department of Psychology, Stanford University, Stanford, CA 94305, USA. turhan.canli@sunysb.edu

Psychological studies have found better memory in women than men for emotional events, but the neural basis for this difference is unknown. We used event-related functional MRI to assess whether sex differences in memory for emotional stimuli is associated with activation of different neural systems in men and women. Brain activation in 12 men and 12 women was recorded while they rated their experience of emotional arousal in response to neutral and emotionally negative pictures. In a recognition memory test 3 weeks after scanning, highly emotional pictures were remembered best, and remembered better by women than by men. Men and women activated different neural circuits to encode stimuli effectively into memory even when the analysis was restricted to pictures rated equally arousing by both groups. Men activated significantly more structures than women in a network that included the right amygdala, whereas women activated significantly fewer structures in a network that included the left amygdala. Women had significantly more brain regions where activation correlated with both ongoing evaluation of emotional experience and with subsequent memory for the most emotionally arousing pictures. Greater overlap in brain regions sensitive to current emotion and contributing to subsequent memory may be a neural mechanism for emotions to enhance memory more powerfully in women than in men.

: J Neurosci 2002 Aug 1;22(15):6810-8

Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons.

Vyas A, Mitra R, Shankaranarayana Rao BS, Chattarji S.

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.

The hippocampus and the amygdala are essential components of the neural circuitry mediating stress responses. The hippocampus, which provides negative feedback regulation of the stress response, is particularly vulnerable to degenerative changes caused by chronic stress. Unlike the hippocampus, relatively little is known about how stress affects the amygdala and the nature of its role in the stress response. Hence, we examined the effects of two different models of chronic stress on hippocampal and amygdaloid neuronal morphology in rats. In agreement with previous reports, chronic immobilization stress (CIS) induced dendritic atrophy and debranching in CA3 pyramidal neurons of the hippocampus. In striking contrast, pyramidal and stellate neurons in the basolateral complex of the amygdala exhibited enhanced dendritic arborization in response to the same CIS. Chronic unpredictable stress (CUS), however, had little effect on CA3 pyramidal neurons and induced atrophy only in BLA bipolar neurons. These results indicate that chronic stress can cause contrasting patterns of dendritic remodeling in neurons of the amygdala and hippocampus. Moreover, CIS, but not CUS, reduced open-arm activity in the elevated plus-maze. These findings raise the possibility that certain forms of chronic stress, by affecting specific neuronal elements in the amygdala, may lead to behavioral manifestations of enhanced emotionality. Thus, stress-induced structural plasticity in amygdala neurons may provide a candidate cellular substrate for affective disorders triggered by chronic stress.

J Cogn Neurosci 2002 Jul 1;14(5):709-20

Is the human amygdala critical for the subjective experience of emotion? Evidence of intact dispositional affect in patients with amygdala lesions.

Anderson AK, Phelps EA.

Stanford University, Stanford, CA, USA.

It is thought that the human amygdala is a critical component of the neural substrates of emotional experience, involved particularly in the generation of fear, anxiety, and general negative affectivity. Although many neuroimaging studies demonstrate findings consistent this notion, little evidence of altered emotional experience following amygdala damage has been gathered in humans. In a preliminary test of the amygdala's role in phenomenal affective states, we assessed the extent of experienced positive and negative affective states in patients with amygdala damage and age-, sex-, and education-matched controls. To assess chronic changes in experienced affect, all groups were administered the Positive and Negative Affect Schedules (PANAS, Watson, Clark, & Tellegen, 1988). In the first study, we examined the effects of amygdala lesions on affective traits in 10 left and 10 right amygdala-damaged patients, 1 patient with bilateral amygdala damage (SP), and 20 control subjects. Subjects were asked to indicate the typicality of different experiential states of positive (e.g., inspired, excited) and negative (e.g., afraid, nervous) valence. In a second study, we examined more closely the effects of bilateral amygdala damage on the day-to-day generation of affective states by administering the PANAS daily for a 30-day period to patient SP and age-, sex-, and education-matched controls. In both experiments, no differences in the magnitude and frequency of self-reported positive or negative affect were found between control subjects and patients with amygdala damage. Moreover, principal components analyses of the covariation among different affects (across individuals in Study 1 and within individuals across days in Study 2) confirmed a two-factor (positive vs. negative) description of experienced affect in controls. A highly similar two-factor description of experienced affect was found in patients with amygdala lesions. This suggests that the underlying structure of affective states was intact following amygdala damage. It is concluded that the human amygdala may be recruited during phenomenal affective states in the intact brain, but is not necessary for the production of these states.

Proc Natl Acad Sci U S A 2002 Aug 20;99(17):11447-51

Dissociable prefrontal brain systems for attention and emotion.

Yamasaki H, LaBar KS, McCarthy G.

Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC 27710, USA.

The prefrontal cortex has been implicated in a variety of attentional, executive, and mnemonic mental operations, yet its functional organization is still highly debated. The present study used functional MRI to determine whether attentional and emotional functions are segregated into dissociable prefrontal networks in the human brain. Subjects discriminated infrequent and irregularly presented attentional targets (circles) from frequent standards (squares) while novel distracting scenes, parametrically varied for emotional arousal, were intermittently presented. Targets differentially activated middle frontal gyrus, posterior parietal cortex, and posterior cingulate gyrus. Novel distracters activated inferior frontal gyrus, amygdala, and fusiform gyrus, with significantly stronger activation evoked by the emotional scenes. The anterior cingulate gyrus was the only brain region with equivalent responses to attentional and emotional stimuli. These results show that attentional and emotional functions are segregated into parallel dorsal and ventral streams that extend into prefrontal cortex and are integrated in the anterior cingulate. These findings may have implications for understanding the neural dynamics underlying emotional distractibility on attentional tasks in affective disorders.

Cereb Cortex 2002 Sep;12(9):998-1003

Sex differences in temporo-limbic and frontal brain volumes of healthy adults.

Gur RC, Gunning-Dixon F, Bilker WB, Gur RE.

Department of Psychiatry, Brain Behavior Laboratory, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA. gur@bbl.med.upenn.edu

Sex differences have been observed in neurobehavioral measures and in neuroanatomic studies. Men and women differ in emotion processing, including perception, experience and expression, most notably reflected in greater male aggression. We examine temporo-limbic and prefrontal structures volumetrically in a large well-characterized sample of healthy adults, applying morphometric methods across cerebral regions that regulate emotions. Quantitative magnetic resonance imaging (MRI) was performed in 116 healthy adults, 57 men and 59 women, age range 18-49 years. We used reliable methods of region of interest identification to examine sex differences in volume of temporo-limbic and frontal regions. An automated tissue segmentation procedure was used to obtain separate measurements for gray and white matter. After correcting for cranial volume, men and women had identical volumes of amygdala and hippocampus, as well as dorsal prefrontal cortex. However, women had larger orbital frontal cortices than men, resulting in highly significant difference in the ratio of orbital gray to amygdala volume (P = 0.002). The larger volume of cortex devoted to emotional modulation may relate to behavioral evidence for sex differences in emotion processing.

J Cogn Neurosci 2000 Jan;12(1):56-77 Related Articles, Links

Specialized neural systems underlying representations of sequential movements.

Harrington DL, Rao SM, Haaland KY, Bobholz JA, Mayer AR, Binderx JR, Cox RW.

Psychology Service 116B, Veterans Affairs Medical Center, 1501 San Pedro SE, Albequerque, NM 87108, USA. j613@unm.edu

The ease by which movements are combined into skilled actions depends on many factors, including the complexity of movement sequences. Complexity can be defined by the surface structure of a sequence, including motoric properties such as the types of effectors, and by the abstract or sequence-specific structure, which is apparent in the relations amongst movements, such as repetitions. It is not known whether different neural systems support the cognitive and the sensorimotor processes underlying different structural properties of sequential actions. We investigated this question using whole-brain functional magnetic resonance imaging (fMRI) in healthy adults as they performed sequences of five key presses involving up to three fingers. The structure of sequences was defined by two factors that independently lengthen the time to plan sequences before movement: the number of different fingers (1-3; surface structure) and the number of finger transitions (0-4; sequence-specific structure). The results showed that systems involved in visual processing (extrastriate cortex) and the preparation of sensory aspects of movement (rostral inferior parietal and ventral premotor cortex (PMv)) correlated with both properties of sequence structure. The number of different fingers positively correlated with activation intensity in the cerebellum and superior parietal cortex (anterior), systems associated with sensorimotor, and kinematic representations of movement, respectively. The number of finger transitions correlated with activation in systems previously associated with sequence-specific processing, including the inferior parietal and the dorsal premotor cortex (PMd), and in interconnecting superior temporal-middle frontal gyrus networks. Different patterns of activation in the left and right inferior parietal cortex were associated with different sequences, consistent with the speculation that sequences are encoded using different mnemonics, depending on the sequence-specific structure. In contrast, PMd activation correlated positively with increases in the number of transitions, consistent with the role of this area in the retrieval or preparation of abstract action plans. These findings suggest that the surface and the sequence-specific structure of sequential movements can be distinguished by distinct distributed systems that support their underlying mental operations.

Nat Neurosci 2001 Mar;4(3):317-23 Related Articles, Links

The evolution of brain activation during temporal processing.

Rao SM, Mayer AR, Harrington DL.

Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

Timing is crucial to many aspects of human performance. To better understand its neural underpinnings, we used event-related fMRI to examine the time course of activation associated with different components of a time perception task. We distinguished systems associated with encoding time intervals from those related to comparing intervals and implementing a response. Activation in the basal ganglia occurred early, and was uniquely associated with encoding time intervals, whereas cerebellar activation unfolded late, suggesting an involvement in processes other than explicit timing. Early cortical activation associated with encoding of time intervals was observed in the right inferior parietal cortex and bilateral premotor cortex, implicating these systems in attention and temporary maintenance of intervals. Late activation in the right dorsolateral prefrontal cortex emerged during comparison of time intervals. Our results illustrate a dynamic network of cortical-subcortical activation associated with different components of temporal information processing.
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: J Neurosci 1997 Jul 15;17(14):5528-35 Related Articles, Links

Distributed neural systems underlying the timing of movements.

Rao SM, Harrington DL, Haaland KY, Bobholz JA, Cox RW, Binder JR.

Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

Timing is essential to the execution of skilled movements, yet our knowledge of the neural systems underlying timekeeping operations is limited. Using whole-brain functional magnetic resonance imaging, subjects were imaged while tapping with their right index finger in synchrony with tones that were separated by constant intervals [Synchronization (S)], followed by tapping without the benefit of an auditory cue [Continuation (C)]. Two control conditions followed in which subjects listened to tones and then made pitch discriminations (D). Both the S and the C conditions produced equivalent activation within the left sensorimotor cortex, the right cerebellum (dorsal dentate nucleus), and the right superior temporal gyrus (STG). Only the C condition produced activation of a medial premotor system, including the caudal supplementary motor area (SMA), the left putamen, and the left ventrolateral thalamus. The C condition also activated a region within the right inferior frontal gyrus (IFG), which is functionally interconnected with auditory cortex. Both control conditions produced bilateral activation of the STG, and the D condition also activated the rostral SMA. These results suggest that the internal generation of precisely timed movements is dependent on three interrelated neural systems, one that is involved in explicit timing (putamen, ventrolateral thalamus, SMA), one that mediates auditory sensory memory (IFG, STG), and another that is involved in sensorimotor processing (dorsal dentate nucleus, sensorimotor cortex).

J Neurosci 2002 Sep 15;22(18):7892-902

Regulation of synaptic plasticity genes during consolidation of fear conditioning.

Ressler KJ, Paschall G, Zhou XL, Davis M.

Department of Psychiatry and Behavioral Sciences, Center for Behavioral Neuroscience, Emory University School of Medicine, Atlanta, Georgia 30322, USA. kressle@emory.edu

In mammals, long-term memory induced by Pavlovian fear conditioning has been shown to be dependent on the amygdala during a protein and mRNA synthesis-dependent phase of memory consolidation. We have used genes identified in a kainic acid model of synaptic plasticity as in situ hybridization probes during the consolidation period after fear conditioning. We found that these genes were transcriptionally regulated in several brain areas only when stimuli were presented in a manner that supported behavioral learning and not after unpaired presentations or footshocks alone. Immediate early genes and neurofilament mRNA peaked approximately 30 min after conditioning, as expected. Interestingly, nurr-1, alpha-actinin, and 16c8 increased approximately 2-4 hr later, whereas neurogranin and gephyrin decreased during that time. Our results suggest that fear memory consolidation occurs within a broad neural circuit that includes, but is not limited to, the amygdala. Together, a broad array of transcriptionally regulated genes, encoding transcription factors, cytoskeletal proteins, adhesion molecules, and receptor stabilization molecules, appear to mediate the neural plasticity underlying specific forms of long-term memory in mammals.

Brain 2002 Oct;125(Pt 10):2286-95

Emotion comprehension in the temporal variant of frontotemporal dementia.

Rosen HJ, Perry RJ, Murphy J, Kramer JH, Mychack P, Schuff N, Weiner M, Levenson RW, Miller BL.

Department of Neurology, Memory and Aging Center, University of California at San Francisco, 350 Parnassus Avenue, Suite 800, Box 1207, San Francisco, CA 94143-1207, USA. howie@itsa.ucsf.edu

Frontotemporal dementia (FTD) is a neurodegenerative disease characterized by behavioural disorders that suggest abnormalities of emotional processing. Patients with the temporal variant of FTD (tvFTD) are particularly at risk for developing deficits in emotional processing secondary to atrophy in the amygdala, anterior temporal cortex (ATC) and orbital frontal cortex (OFC), structures that are components of the brain's emotional processing systems. In addition, previous studies have suggested that predominantly right, as opposed to left temporal atrophy is more likely to be associated with behavioural and emotional impairments in tvFTD. However, emotional processing has never been assessed directly in this group. We examined one aspect of emotional processing, namely the comprehension of facial expressions of emotion (emotional comprehension) in nine individuals with tvFTD, and correlated performance on this measure with atrophy (as measured from T(1)-weighted MRI scans by region of interest analysis) in the amygdala, ATC and OFC. Compared with age-matched controls, the tvFTD group was impaired in emotional comprehension, with more severe impairment for emotions with negative valence, including sadness, anger and fear, than for happiness. Emotional comprehension was correlated with atrophy in the right amygdala and the right OFC, and not with atrophy in other structures. When individual profiles of amygdala atrophy were examined across patients and compared with control values, right amygdala atrophy was always accompanied by left amygdala atrophy, whereas patients with volume loss in the left amygdala could have normal or decreased right amygdala volumes. Thus, emotional comprehension appeared to be most impaired when bilateral amygdala atrophy was present, and was not associated with the degree of left amygdala atrophy. Our data indicate that tvFTD is associated with impairments in emotional processing that may underlie some behavioural problems in this disorder, and that the emergence of such deficits depends on the specific pattern of anatomical injury. These results have implications both for the clinical presentation in tvFTD patients and for the study of the neuroanatomical basis of emotion.

Int J Neurosci 2002 Jun;112(6):605-12

A relationship between smell identification and empathy.

Spinella M.

Division of Social and Behavioral Sciences, Richard Stockton College of New Jersey, P.O. Box 195, Pomona, NJ 08240-0195, USA. marcello.spinella@stockton.edu

Olfaction is a sense that has close relationships with the limbic system and emotion. Empathy is a vicarious feeling of others' emotional states. The two functions are known to be subserved by common neuroanatomical structures, including orbitofrontal cortex, mediodorsal thalamus, and the amygdala. This study demonstrates a correlation between smell identification and empathy, using the Mehrabian and Epstein Empathy Questionnaire and Alberta Smell Test. Right nostril smell identification correlated with empathy, whereas the left nostril did not. Given the predominantly ipsilateral representation in the olfactory system, this is in accordance with right hemisphere dominance for emotional functions and empathy. Further, the emotional component of empathy (feeling another's emotions) correlated with smell, whereas a cognitive component (comprehending another's emotions) did not. This study is the first to demonstrate a relationship between empathy and smell in normal subjects, suggesting common neural substrates.

J Comp Neurol 2002 Nov 11;453(2):116-30

Amygdalo-cortical sprouting continues into early adulthood: Implications for the development of normal and abnormal function during adolescence.

Cunningham MG, Bhattacharyya S, Benes FM.

Laboratory of Structural Neuroscience, McLean Hospital; Program in Neuroscience and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02478.

Adolescence is a critical stage for the development of emotional maturity and diverse forms of psychopathology. The posterior basolateral nucleus of the amygdala is known to mediate fear and anxiety and is important in assigning emotional valence to cognitive processes. The medial prefrontal cortex, a homologue of the human anterior cingulate cortex, mediates emotional, attentional, and motivational behaviors at the cortical level. We postulate that the development of connectivity between these two corticolimbic regions contributes to an enhanced integration of emotion and cognition during the postnatal period. In order to characterize the development of this relay, injections of the anterograde tracer biocytin were stereotaxically placed within the posterior basolateral nucleus of the amygdala of rats at successive postnatal time points (postnatal days 6-120). Labeled fibers in the medial prefrontal cortex were evaluated using a combination of brightfield, confocal, and electron microscopy. We found that the density of labeled fibers originating from the posterior basolateral nucleus shows a sharp curvilinear increase within layers II and V of the anterior cingulate cortex and the infralimbic subdivisions of medial prefrontal cortex during the late postweanling period. This increase was paralleled by a linear rise in the number of axospinous and axodendritic synapses present in the neuropil. Based on these results, we propose that late maturation of amygdalo-cortical connectivity may provide an anatomical basis for the development and integration of normal and possibly abnormal emotional behavior during adolescence and early adulthood. J. Comp. Neurol. 453:116-130, 2002. Copyright 2002 Wiley-Liss, Inc.

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Nature, 2002 Sep 19;419(6904):269-270

Neuropsychology: Stimulating illusory own-body perceptions.

Blanke O, Ortigue S, Landis T, Seeck M.

'Out-of-body' experiences (OBEs) are curious, usually brief sensations in which a person's consciousness seems to become detached from the body and take up a remote viewing position. Here we describe the repeated induction of this experience by focal electrical stimulation of the brain's right angular gyrus in a patient who was undergoing evaluation for epilepsy treatment. Stimulation at this site also elicited illusory transformations of the patient's arm and legs (complex somatosensory responses) and whole-body displacements (vestibular responses), indicating that out-of-body experiences may reflect a failure by the brain to integrate complex somatosensory and vestibular information.
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Cognition 2001 Dec;82(2):157-78

Error monitoring in the hemispheres: the effect of lateralized feedback on lexical decision.

Kaplan JT, Zaidel E.

Department of Psychology, University of California, Los Angeles, CA 90095-1563, USA. jonask@ucla.edu

Does each hemisphere have its own system for monitoring and responding to errors? Three experiments investigate the effect of presenting lateralized accuracy feedback in a bilateral lexical decision task. We presented feedback after each trial in either the left visual field (LVF) or right visual field (RVF). In Experiment 1 the feedback stimuli were faces smiling or frowning, in Experiment 2 we used colored squares, and Experiment 3 tested the effect of verbal feedback. Negative feedback presented in the LVF tended to improve performance on the following trial, while the same negative feedback in the RVF tended to disrupt performance on the following trial. This result was strongest with the faces as feedback, was less pronounced with colored squares, and disappeared with verbal feedback. The results are interpreted as suggesting a right hemisphere superiority for error monitoring that depends on the mode of feedback.

Int J Neurosci 2002 Jun;112(6):743-57

Lateralized changes in autonomic arousal during emotional processing in patients with unilateral temporal lobe seizure onset.

Lee GP, Meador KJ, Loring DW, Bradley KP.

Department of Occupational Therapy, School of Allied Health, Department of Neurology, School of Medicine, Medical College of Georgia, Augusta, Georgia, USA. glee@mail.mcg.edu

The valence model of emotion, which posits cerebral lateralization for positive and negative emotional processing, was investigated in patients with unilateral mesial temporal lobe epilepsy (TLE) and controls by measuring skin conductance levels (SCLs) and heart rate (HR) while positive and negative emotional photographs were viewed. Left TLEs exhibited selective SCL hyperarousal when viewing negative emotional slides relative to controls and right TLEs. In contrast, right TLEs showed no significant differences compared with the other groups. Results are consistent with left hemispheric specialization for positive emotional expression. Dysfunction of left mesial temporal lobe structures may result in autonomic hyperarousal and a release of the unrestrained negative emotional tendencies of the right hemisphere.

J Neurophysiol 2002 Aug;88(2):771-82

Local field potential oscillations in primate cerebellar cortex: modulation during active and passive expectancy.

Courtemanche R, Pellerin JP, Lamarre Y.

Departement de Physiologie and Centre de Recherche en Sciences Neurologiques, Universite de Montreal, Quebec H3C 3J7, Canada.

Cerebellar local field potential (LFP) oscillations were recorded in the paramedian lobule of one hemisphere, while monkeys were in two behavioral conditions: actively performing an elbow flexion-extension or a lever-press task in response to an auditory or visual stimulus to get reward (active condition), or waiting quietly for the reward to come in the same time window after the appearance of the stimulus (passive condition). The oscillations in the paramedian lobule were first characterized in four monkeys, and they showed an idiosyncratic frequency for each monkey, between 13 and 25 Hz. The granule cell layer multi-unit activity was phase-locked with the negative phase of the LFP oscillations, while Purkinje cell simple spikes were also sometimes phase-locked with the LFP. Three monkeys were trained to perform the motor tasks: the LFP oscillations were modulated, in the active condition, in a systematic manner in relation to the lever-press or elbow flexion-extension tasks. During periods when the monkey was waiting to initiate movement, LFP oscillations appeared and then stopped with movement initiation. This modulation was valid for the task being executed with either hand. Surprisingly, the LFP oscillations were also systematically modulated during the passive condition; as the monkey was waiting for the usual time to get a reward passively, oscillations appeared stronger and were stopped by the end of the usual delay, whether the monkey was rewarded or not. This type of modulation was not affected by the length of the stimulus, as long as the reward window was known to the monkey. If the monkey had not been previously trained to the active condition, the modulation appeared in the passive condition. These results show that cerebellar LFP oscillations in the paramedian lobule are reliably present when the monkey is involved in a waiting period, whether this period ends with an active or passive event. This study provides electrophysiological evidence for a specific pattern of activity in the cerebellum for the expectancy of events that are known to be bound to happen, either externally, or from voluntary action.

Psychiatr Pol 2002 May-Jun;36(3):421-34

[Emotional behavior in schizophrenia and one-sided brain damage. Cerebral hemispheric asymmetry. Part I]

[Article in Polish]

Kucharska-Pietura K, Hunca-Bednarska A.

Katedry i Kliniki Psychiatrii AM w Lublinie.

Although, emotions play a crucial role in schizophrenia, the changes in emotional dimension in relation to brain asymmetry still remain controversial. The aim of our work was: 1) to compare the emotional behaviour between the examined groups: S--non-chronic schizophrenic patients (n = 50), CS--chronic schizophrenic patients (n = 50), N--healthy controls (n = 50), R--right brain-damaged patients (n = 30), and L--left brain-damaged patients (n = 30), 2) to assess the changes in attitude processes and in types of emotional reactions, its relation to lateralised hemisphere damage and chronicity of the schizophrenic process. All psychiatric subjects were diagnosed as paranoid schizophrenics according to DSM-IV criteria and were scored on the PANSS scale after four weeks of neuroleptic treatment. Brain-damaged patients were included if they experienced single-episode cerebrovascular accidents causing right or left hemisphere damage (confirmed in CT scan reports). The neurological patients were examined at least 3 weeks after the onset of the episode. Emotional behaviour was assessed using Observational Scale of Emotional Behaviour aimed at the evaluation of: A) attitude processes B) the emotional reactions. Our results revealed differentiated type of emotional behaviour in the examined population. Right brain-damaged patients significantly often revealed elevated mood, lack of adequacy of self-evaluation and active or negative attitude towards the environment. Left brain-damaged patients showed depressed mood, resignation, positive or seldom passive attitude to others and adequate self-evaluation. Schizophrenic patients mostly revealed indifferent mood and passive attitude to environment, their self-evaluation was rather adequate. Based on our data, the changes in emotional behaviour in schizophrenic patients might reflect frontal lobes dysfunction rather than dysfunction localised in one of cerebral hemispheres.
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Neuropsychiatry Neuropsychol Behav Neurol 2002 Jun;15(2):72-8

The perception of emotional chimeric faces in schizophrenia: further evidence of right hemisphere dysfunction.

Kucharska-Pietura K, David AS, Dropko P, Klimkowski M.

Department of Psychological Medicine, University Medical School, Lublin, Poland.

OBJECTIVE: To examine lateral perceptual bias, an index of right hemisphere function, and its relation to performance on a standard facial perception test and to clinical variables in a large sample of first episode and chronic schizophrenia. BACKGROUND: Judgments made on chimeric faces reliably elicit a perceptual bias to the left hemispace, presumed to be a result of right hemisphere dominance for spatial attention. Recent studies have suggested that this bias is reduced or absent in people with schizophrenia. METHODS: Fifty first-episode and 50 patients with chronic schizophrenic and 50 control subjects were given a brief neuropsychologic battery that included a Happy-Sad Chimeric Face test and the Benton Facial Recognition Test. All patients were rated on the Positive and Negative Syndrome Scale of Schizophrenia after 4 weeks of neuroleptic treatment. All were right handed RESULTS: The patients with schizophrenia showed a significantly weaker perceptual left hemispatial bias compared with controls. In fact the mean bias was in the opposite direction in the chronic group. There was no correlation between left hemispatial bias and either positive or negative symptoms, current medication dose, or mood. Results from the Benton test revealed a performance deficit among the patients with schizophrenia compared with controls but was not correlated with performance on the chimeric faces test in the patients. CONCLUSIONS: The results confirm a specific deficit in right hemisphere attentional functions in schizophrenia, which is separate from a general impairment in facial processing. The deficit is most marked in chronic patients but further study is required to determine whether this is a consequence of prolonged illness.

Acta Neurobiol Exp (Warsz) 2002;62(1):33-43

Perception of facial affect in chronic schizophrenia and right brain damage.

Kucharska-Pietura K, Klimkowski M.

Department of Psychiatry, University Medical School, 2 Abramowicka St., 20-442 Lublin, Poland. katepietura@hotmail.com

This study was designed to compare the performance of 50 chronic schizophrenics (CS) to that of 30 right brain-damaged patients (R), and 50 healthy controls (N) on several facial perception measures: Emotion Labelling and Recognition, and the Benton Facial Recognition Test. CSs were diagnosed according to DSM-IV criteria and their psychiatric state was assessed using the PANSS scale. All subjects were right handed. Their cognitive state was assessed using the MMSE. Subjects rated their current mood on a visual analogue scale. The results showed that the CSs and Rs were significantly impaired compared to Ns for the emotional tasks but did not differ from each other. Moreover, the patient groups were significantly less accurate in recognising emotionally neutral facial stimuli. Each subject group had more difficulty processing negative relative to positive affect. The deficit in schizophrenia was found to be stable, which may reflect a trait-like, rather than a state-dependent, characteristic. Moreover, some support is provided for the notion that facial affect perception in chronic schizophrenia is associated with right hemisphere dysfunction.

(IDM perspetive : *** alternative link is the left takes over to compensate for the damaged right - this is identifed elsewhere. IOW the schizzyness is a consequence of left brain dominating and so its 'natural' characteristics pop out but are distorted due to a lack of integrating skills usually dominated in the right)

Neuropsychologia 2002;40(9):1601-7

Cerebral hemispheric differences in memory of emotional and non-emotional words in normal individuals.

Nagae S, Moscovitch M.

Department of Psychology, Fukuoka University of Education, Munakata, Fukuoka, Japan. nagaex@fukuoka-edu.ac.jp

The present study was designed to examine the cerebral hemispheric differences in memory of positive, negative and non-emotional words using a new method of successive presentation to each visual half-field in which perception of each item was nearly perfect thereby allowing laterality differences for effects of emotion on memory to emerge unconfounded by perception (Experiment 1). This procedure was compared with traditional perceptual identification (Experiment 2). In Experiment 1, 12 words were presented successively in each half field in each trial followed by free recall at the end of the trial. The results showed that recall of positive and negative emotional words was better than that of non-emotional words in both visual fields. Recall of positive and negative emotional words was not different in left and right visual fields (RVFs) although the recall of non-emotional words was better in the RVF than in the left visual field (LVF). The differences in recall between emotional and non-emotional words was greater in the LVF than in the RVF. Experiment 2 used the more traditional method of perceptual identification following each visual half-field presentation of a single item. Perceptual identification was better in the RVF than the LVF in each word condition. There were no visual field differences in perceptual identification between emotional and non-emotional words, as there was for memory in Experiment 1. The results supported the hypothesis that explicit memory for emotional words was dependent more on the right hemisphere, whereas perception of both emotional and non-emotional words was more dependent on the left hemisphere

Semin Speech Lang 2002 May;23(2):117-28

Unilateral neglect: a disorder of attention.

Cherney LR.

Rehabilitation Institute of Chicago and Department of Physical Medicine and Rehabilitation, Northwestern University Medical School, Chicago, Illinois, USA. Lcherney@rehabchicago.org

Unilateral neglect is a complex disorder that occurs most frequently in patients with right hemisphere damage. Although it is most severe in the acute phase, it may be detectable in some patients many months and even years after onset. Its presence is usually obvious in functional activities, including reading and writing, and it has consistently been identified as a negative predictor for recovery of independence in daily living. The purposes of this article are to review common neglect symptoms, summarize current theories of neglect, outline appropriate assessment tasks, and describe several treatment approaches for left unilateral visual neglect.

Int J Neurosci 2001;110(3-4):197-219

Event-related synchronization and desynchronization during affective processing: emergence of valence-related time-dependent hemispheric asymmetries in theta and upper alpha band.

Aftanas L, Varlamov A, Pavlov S, Makhnev V, Reva N.

Psychophysiology Laboratory, State Research Institute of Physiology, Siberian Branch, Russian Academy of Medical Sciences, Timakova str. 4, 630117, Novosibirsk, Russia. aftanas@iph.ma.nsc.ru

Event-related desynchronization (ERD) and synchronization (ERS) in the individually defined theta, alpha-1, alpha-2, and alpha-3 frequency bands were measured in 22 healthy subjects (Ss) in response to neutral (Neut), emotionally positive (Pos), and negative (Neg) IAPS stimuli. The 62-channel EEG, facial EMG and ECG were simultaneously recorded while subjects viewed sequentially presented pictures and subjectively rated them after each presentation. The obtained findings indicate that differences induced by pictures varying in emotional valence are associated mainly with increased theta and alpha-3 synchronization activity and anterior hemispheric asymmetries. In the anterior temporal leads theta ERS revealed a significant valence by hemisphere interaction showing relatively greater right hemisphere theta ERS for Neg and left hemisphere ERS for Pos stimuli in the time window of 100-700 ms post-stimulus, whereas in the alpha-3 band Neg stimuli induced lateralized time-dependent left hemisphere ERS increased in the time window of 800-1200 ms, were not observed for Neut and Pos stimuli. The obtained results along with earlier observations on EEG correlates of affective processing challenge the notion that affective anterior hemispheric asymmetries are mainly sensitive to wide alpha frequency band. Frequency and time dependence of anterior hemispheric asymmetries in emotional valence discrimination is emphasized.

J Pers Soc Psychol. 2001 Nov;81(5):922-34.

Attending holistically versus analytically: comparing the context sensitivity of Japanese and Americans.

Masuda T, Nisbett RE.

Department of Psychology, University of Michigan, Ann Arbor 48109-1109, USA. tmasuda@umich.edu

Much research indicates that East Asians, more than Americans, explain events with reference to the context. The authors examined whether East Asians also attend to the context more than Americans do. In Study 1, Japanese and Americans watched animated vignettes of underwater scenes and reported the contents. In a subsequent recognition test, they were shown previously seen objects as well as new objects, either in their original setting or in novel settings, and then were asked to judge whether they had seen the objects. Study 2 replicated the recognition task using photographs of wildlife. The results showed that the Japanese (a) made more statements about contextual information and relationships than Americans did and (b) recognized previously seen objects more accurately when they saw them in their original settings rather than in the novel settings, whereas this manipulation had relatively little effect on Americans.

Neuropsychologia 2002;40(7):730-47

Picture the difference: electrophysiological investigations of picture processing in the two cerebral hemispheres.

Federmeier KD, Kutas M.

Department of Cognitive Science, University of California-San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0515, USA. kfederme@cogsci.ucsd.edu

The nature of semantic memory and the role of the two cerebral hemispheres in meaning processing were examined using event-related brain potentials (ERPs) elicited by pictures in sentences. Participants read sentence pairs ending with the lateralized presentation of three target types: (1) expected pictures, (2) unexpected pictures from the expected semantic category, and (3) unexpected pictures from an unexpected category. ERPs to contextually unexpected pictures were more negative 350-500ms (larger N400s) than those to expected pictures in both visual fields. However, while N400s to the two types of unexpected items did not differ with left visual field presentations, they were smaller to the unexpected items from the expected category with right visual field presentations. This pattern, previously observed to words [Brain Language 62 (1998) 149], suggests general differences in how the two hemispheres use context on-line. Other aspects of the N400 response-and effects on earlier ERP components-reveal differences between pictures and words, suggesting that semantic memory access is not modality-independent. The P2 component varied with ending type for right but not left visual field presentations, suggesting that the left hemisphere may use contextual information to prepare for the visual analysis of upcoming stimuli. Furthermore, there was clear evidence for an earlier negativity ("N300"), which varied with ending type but, unlike the N400, was unaffected by visual field of presentation. Overall, the results support our hypothesis that the left hemisphere actively uses top-down information to preactivate perceptual and semantic features of upcoming stimuli, while the right hemisphere adopts a "wait and see" integrative approach.

(IDM focus : *** proactive, 'as interpreted' nature of LH vs more reactive, integrating, 'as is' nature of RH)

Brain Lang 2002 Mar;80(3):269-86

Dissociating prelexical and postlexical processing of affective information in the two hemispheres: effects of the stimulus presentation format.

Windmann S, Daum I, Gunturkun O.

Department of Biopsychology, Ruhr-University Bochum, Germany. Sabine.Windmann@ruhr-uni-bochum.de

Using a lexical decision task, the authors investigated whether brain asymmetries in the detection of emotionally negative semantic associations arise only at a perceptually discriminative stage at which lexical analysis is accurate or can already be found at crude and incomplete levels of perceptual representation at which word-nonword discrimination is based solely on guessing. Emotionally negative and neutral items were presented near perceptual threshold in the left and right visual hemifields. Word-nonword discrimination performance as well as the bias to classify a stimulus as a "word" (whether or not it actually is a word) were assessed for a normal, horizontal stimulus presentation format (Experiment 1) and for an unusual, vertical presentation format (Experiment 2). Results show that while the two hemispheres are equally able to detect affective semantic associations at a prelexical processing stage (both experiments), the right hemisphere is superior at a postlexical, perceptually discriminative stage (Experiment 2). Moreover, the findings suggest that only an unusual, nonoverlearned stimulus presentation format allows adequate assessment of the right hemisphere's lexical-semantic skills. Copyright 2002 Elsevier Science (USA).
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Int J Neurosci 2001 Jul;109(1-2):127-37

The effect of total sleep deprivation on cognitive functions in normal adult male subjects.

Kim DJ, Lee HP, Kim MS, Park YJ, Go HJ, Kim KS, Lee SP, Chae JH, Lee CT.

Department of Psychiatry, College of Medicine, Catholic University of Korea. kdj922@chollian.net

This study was conducted to evaluate the effect of acute sleep deprivation on cognitive functions. A total of 18 healthy right handed males were deprived of sleep for 24 hours. Luria-Nebraska Neuropsychological Battery and calculation & digit-span subtest of K-WAIS were administered before and after sleep deprivation in order to examine the changes of cognitive functions. There were no differences in freedom from distractibility, tacile function, visual function, reading, writing, arithmetic and intellectual process function. However, the cognitive functions such as motor, rhythm, receptive & expressive speech, memory and complex verbal arithmetic function were decreased after sleep deprivation. All of these functions are known to be related to the right anterior hemisphere. For localization scales, the scores of right frontal and right temporal dysfunction scale were increased after sleep deprivation. These results indicate that sleep deprivation has a negative effect on cognitive functions, especially those associated with right anterior hemisphere or subcortical areas.

Integr Physiol Behav Sci 2001 Apr-Jun;36(2):137-53

The color-vision approach to emotional space: cortical evoked potential data.

Boucsein W, Schaefer F, Sokolov EN, Schroder C, Furedy JJ.

Physiological Psychology, University of Wuppertal, Germany. boucsein@uni-wuppertal.de

A framework for accounting for emotional phenomena proposed by Sokolov and Boucsein (2000) employs conceptual dimensions that parallel those of hue, brightness, and saturation in color vision. The approach that employs the concepts of emotional quality. intensity, and saturation has been supported by psychophysical emotional scaling data gathered from a few trained observers. We report cortical evoked potential data obtained during the change between different emotions expressed in schematic faces. Twenty-five subjects (13 male, 12 female) were presented with a positive, a negative, and a neutral computer-generated face with random interstimulus intervals in a within-subjects design, together with four meaningful and four meaningless control stimuli made up from the same elements. Frontal, central, parietal, and temporal ERPs were recorded from each hemisphere. Statistically significant outcomes in the P300 and N200 range support the potential fruitfulness of the proposed color-vision-model-based approach to human emotional space.

Neurosci Lett 2002 Feb 15;319(2):99-102

A left-prefrontal lateralized, sympathetic mechanism directs attention towards social threat in humans: evidence from repetitive transcranial magnetic stimulation.

van Honk J, Hermans EJ, d'Alfonso AA, Schutter DJ, van Doornen L, de Haan EH.

Helmholtz Research Institute, Affective Neuroscience Section, Utrecht University, Heidelberglaan 2, 3584 CS Utrecht, The Netherlands. j.vanhonk@fss.uu.nl

The prioritized processing of threat is suggested to be motivated by anxiety, regulated by the parasympatheticus, and biased to the right hemisphere. However, according to an anterior dimensional model of negative affect this is unlikely to be true when threat is of social origin. Social threat is communicated by the angry facial expression, and recent research indicates that prioritized processing of angry faces is motivated by anger. Anger is a sympathetically dominated emotion, and for its expression and experience, neuroimaging data have demonstrated anterior lateralization to the left hemisphere. To scrutinize the above diverging statements, suprathreshold low-frequency repetitive transcranial magnetic stimulation (rTMS) was applied over the right and the left prefrontal cortex (PFC) of ten healthy subjects during 15min continuously, and the subsequent effects on sympathetic and parasympathetic activity of the heart, and selective attention to angry facial expressions were investigated. Combined rTMS-neuroimaging studies have shown contralateral excitation after unilateral supratheshold low-frequency rTMS, hence the strengthening of contralaterally mediated emotion functions. The earlier reported increases in selective attention to angry facial expressions after right-PFC rTMS were found to be accompanied by and significantly associated with elevations in sympathetic activity. Our data suggest that a left-PFC lateralized, sympathetic mechanism directs attention towards the angry facial expression.

(IDM focus: *** The IDM categorisation of Plutchik's dichotomies of emotion mapped anger to the differentiation realm - single context, intense expression - above supports this re left brain single context)

Psychiatry Res 2001 Nov 30;108(2):65-78

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study.

Wible CG, Anderson J, Shenton ME, Kricun A, Hirayasu Y, Tanaka S, Levitt JJ, O'Donnell BF, Kikinis R, Jolesz FA, McCarley RW.

Department of Psychiatry, Harvard Medical School, Boston, MA, USA.

The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial-temporal lobe regions - two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal-prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.

Cogn Affect Behav Neurosci 2001 Sep;1(3):239-49 Related Articles, Links

An fMRI study of imagined self-rotation.

Creem SH, Downs TH, Wraga M, Harrington GS, Proffitt DR, Downs JH 3rd.

University of Utah, Department of Psychology, 380 S. 1530 E. Rm. 502, Salt Lake City, UT 84112, USA. sarah.creem@psych.utah.edu

In the present study, functional magnetic resonance imaging was used to examine the neural mechanisms involved in the imagined spatial transformation of one's body. The task required subjects to update the position of one of four external objects from memory after they had performed an imagined self-rotation to a new position. Activation in the rotation condition was compared with that in a control condition in which subjects located the positions of objects without imagining a change in self-position. The results indicated similar networks of activation to other egocentric transformation tasks involving decisions about body parts. The most significant area of activation was in the left posterior parietal cortex. Other regions of activation common among several of the subjects were secondary visual, premotor, and frontal lobe regions. These results are discussed relative to motor and visual imagery processes as well as to the distinctions between the present task and other imagined egocentric transformation tasks.

Dev Cell 2001 Aug;1(2):179-86

Mechanisms of left-right asymmetry: what's right and what's left? [zebra fish data]

Wright CV.

Department of Cell Biology, Vanderbilt University Medical School, Nashville, Tennessee 37232, USA. chris.wright@mcmail.vanderbilt.edu

A recent meeting at the Juan March Foundation in Madrid, Spain, covered current understanding of the pathways and mechanisms involved in generating left-right asymmetry.

Biol Psychiatry 2001 Sep 15;50(6):447-52

Event-related potentials in schizophrenia during tonal and phonetic oddball tasks: relations to diagnostic subtype, symptom features and verbal memory.

Bruder GE, Kayser J, Tenke CE, Friedman M, Malaspina D, Gorman JM.

Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.

BACKGROUND: This study compares event-related potentials for paranoid patients (n = 13) versus matched undifferentiated patients and unmedicated patients (n = 14) versus matched healthy adults. METHODS: Event-related potentials of right-handed patients and control subjects were recorded from 30 electrodes during oddball tasks using consonant-vowel syllables or complex tones. Patients were also assessed using the Positive and Negative Syndrome Scale, the Thought Disorder Index, and the Wechsler Memory Scale. RESULTS: Paranoid patients did not differ from undifferentiated patients in N1 or P3 amplitude but showed larger N2 at frontocentral sites to phonetic stimuli, as well as larger N2 over left than right hemisphere. Unmedicated patients showed reduced N2, but not N1 or P3, compared to control subjects. CONCLUSIONS: The N2 findings are consistent with neuropsychological evidence of greater verbal abilities and left hemisphere dominance in paranoid than nonparanoid schizophrenia. The findings also confirm the relationship of P3 to total Brief Psychiatric Rating Scale score, negative symptoms, and verbal associative memory.
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Schizophr Res 2001 May 30;50(1-2):19-26

Cerebral gray and white matter reductions and clinical correlates in patients with early onset schizophrenia.

Paillere-Martinot M, Caclin A, Artiges E, Poline JB, Joliot M, Mallet L, Recasens C, Attar-Levy D, Martinot JL.

Service Hospitalier Frederic Joliot, DSV-CEA, and INSERM U.334, 4 place du general Leclerc, 91406 Orsay, France. ml.paillere@psl.ap-hop-paris.fr

Few magnetic resonance imaging studies of schizophrenia have investigated brain tissue volumes and their relation to clinical symptoms in patients with an early age at illness onset. The twofold purpose of the study was to investigate both gray and white matter volumes in schizophrenic men with an early age at illness onset, and to determine whether clinical features correlated with tissue volume changes, using an automated voxel-by-voxel image analysis procedure. Twenty male patients with DSM-IV diagnoses of schizophrenia, and an early age at onset (m+/-SD=19+/-2) were compared with 20 age-matched health men. Magnetic resonance (1.5-T) scans were obtained with an Inversion-Recovery prepared fast gradient echo sequence enhancing gray and white matter contrast. Statistical Parametric Mapping was used for image segmentation and comparison. Patients had significant gray matter reductions in medial frontal gyri, left insula, left parahippocampus, and left fusiform gyrus; bilateral white matter reductions in frontal lobes, and increased total cerebrospinal fluid volume were also observed. Negative symptom scores were negatively related to white matter volumes in cingulate regions, and in the right internal capsule. These findings emphasize a pattern of left-hemisphere gray matter abnormalities, and suggest that fronto-paralimbic connectivity may be altered in men with early onset schizophrenia.

J Clin Exp Neuropsychol 2001 Feb;23(1):121-36

The role of functional neuroimaging in the neuropsychology of depression.

Liotti M, Mayberg HS.

Research Imaging Center, and Department of Radiology, Psychiatry and Medicine (Neurology), University of Texas Health Science Center, San Antonio, TX, USA. liotti@uthscsa.edu

Depressed individuals show impaired performance in tests of attention and concentration. They also exhibit PET resting state abnormalities in dorsal prefrontal cortex and anterior cingulate, regions known to be substrates of attentional processing in healthy individuals. This chapter outlines a strategy to study neuropsychological mechanisms in emotional disorders using functional imaging methods. It reviews evidence strongly implicating the dorsolateral prefrontal cortex, particularly in the right hemisphere, as a key brain structure in emotion/cognition interactions in negative mood states. It will be argued that this neocortical region is a crucial convergence zone, being the substrate of sustained attention to the external environment, and the main target of limbic-cortical influences during changes in mood state across health and disease.
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Neurosci Biobehav Rev 2000 Dec;24(8):799-815

The prisoners of despair: right hemisphere deficiency and suicide.

Weinberg I.

P.O. Box 331, 54103, Giv'at-Shemuel, Israel. igor73@internet-zahav.net.il

This paper presents an integrative approach to understanding of the inner experience of suicidal persons in terms of hemispheric asymmetry. The right hemisphere is involved in formation of polysemantic context. Polysemantic context is determined by multiple interconnections among its elements, while each concrete element bears the stamp of the whole context. Left hemisphere functioning leads to formation of monosemantic context. It is suggested that due to functional insufficiency of the right hemisphere the suicidal person demonstrates a compensatory shift to left hemisphere functioning. This shift manifests itself in reversed asymmetry of neurotransmitters, tendency to dissociation, alienated and negative perception of the body, lower sensitivity to pain, disintegration of self-representation, cognitive constriction, overly general nature of personal memories, difficulties in affect regulation as well as such personality traits as low openness to experience and personal constriction. This hypothesis raises a number of suggestions for future research.

Arch Gen Psychiatry 2001 Apr;58(4):334-41
Comment in:
Arch Gen Psychiatry. 2001 Apr;58(4):342-4.

Neural activity related to drug craving in cocaine addiction.

Kilts CD, Schweitzer JB, Quinn CK, Gross RE, Faber TL, Muhammad F, Ely TD, Hoffman JM, Drexler KP.

Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, 1639 Pierce Dr, Suite 4000, PO Drawer AF, Atlanta, GA 30322, USA. sdpcdk@emory.edu

BACKGROUND: Crack cocaine dependence and addiction is typically associated with frequent and intense drug wanting or craving triggered by internal or environmental cues associated with past drug use. METHODS: Water O 15 positron emission tomography (PET) studies were used to localize alterations in synaptic activity related to cue-induced drug craving in 8 crack cocaine-dependent African American men. In a novel approach, script-guided imagery of autobiographical memories were used as individualized cues to internally generate a cocaine craving state and 2 control (ie, anger and neutral episodic memory recall) states during PET image acquisition. RESULTS: The mental imagery of personalized drug use and anger-related scripts was associated with self-ratings of robust drug craving or anger, and comparable alterations in heart rate. Compared with the neutral imagery control condition, imagery-induced drug craving was associated with bilateral (right hemisphere amygdala activation greater than left) activation of the amygdala, the left insula and anterior cingulate gyrus, and the right subcallosal gyrus and nucleus accumbens area. Compared with the anger control condition, internally generated drug craving was associated with bilateral activation of the insula and subcallosal cortex, left hippocampus, and anterior cingulate cortex and brainstem. A brain-wide pixel-by-pixel search indicated significant positive and negative correlations between imagery-induced cocaine craving and regional cerebral blood flow (rCBF) in distributed sites. CONCLUSIONS: The collected findings suggest the craving-related activation of a network of limbic, paralimbic, and striatal brain regions, including structures involved in stimulus-reward association (amygdala), incentive motivation (subcallosal gyrus/nucleus accumbens), and anticipation (anterior cingulate cortex).

: Neuropsychology 2001 Oct;15(4):607-16

Superior episodic memory is associated with interhemispheric processing.

Christman SD, Propper RE.

Department of Psychology, University of Toledo, Ohio 43606, USA. schrist2@uoft02.utoledo.edu

The dependence of episodic memories on interhemispheric processing was tested. In Experiment 1, positive familial sinistrality (FS+; e.g., presence of left-handed relatives) was associated with superior episodic memory and inferior implicit memory in comparison with negative familial sinistrality (i.e., FS-). This reflected a greater degree of interhemispheric interaction in FS+ participants, which was hypothesized as facilitating episodic memory. In Experiment 2, the authors directly manipulated inter- versus intrahemispheric processing using tests of episodic (recognition) and semantic (lexical decision) memory in which letter strings were presented twice within trial blocks. Semantic memory was superior when the 2nd presentation went to the same hemisphere as the 1st. Episodic memory, however, was superior when the 2nd presentation of a stimulus went to the opposite hemisphere. Results support an interhemispheric processing basis for episodic memories.

Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 17, 11531-11536, August 20, 2002

Psychology
Selective impairment of reasoning about social exchange in a patient with bilateral limbic system damage

Valerie E. Stone *, Leda Cosmides , John Tooby , Neal Kroll , and Robert T. Knight ¶||
*Developmental Cognitive Neuroscience Program, University of Denver, 2155 South Race Street, Denver, CO 80208-2478; Center for Evolutionary Psychology, University of California, Santa Barbara, CA 93106; Department of Psychology, Young Hall, University of California, Davis, CA 95616; ¶Department of Psychology and the Helen Wills Neuroscience Institute, Tolman Hall, University of California, Berkeley, CA 94720; and ||Martinez Veterans Medical Center, Martinez, CA 94553

Communicated by Roger N. Shepard, Stanford University, Stanford, CA, June 12, 2002 (received for review December 24, 2001)

Social exchange is a pervasive feature of human social life. Models in evolutionary biology predict that for social exchange to evolve in a species, individuals must be able to detect cheaters (nonreciprocators). Previous research suggests that humans have a cognitive mechanism specialized for detecting cheaters. Here we provide neurological evidence indicating that social exchange reasoning can be selectively impaired while reasoning about other domains is left intact. The patient, R.M., had extensive bilateral limbic system damage, affecting orbitofrontal cortex, temporal pole, and amygdala. We compared his performance on two types of reasoning problem that were closely matched in form and equally difficult for control subjects: social contract rules (of the form, "If you take the benefit, then you must satisfy the requirement") and precaution rules (of the form, "If you engage in hazardous activity X, then you must take precaution Y"). R.M. performed significantly worse in social contract reasoning than in precaution reasoning, when compared both with normal controls and with other brain-damaged subjects. This dissociation in reasoning performance provides evidence that reasoning about social exchange is a specialized and separable component of human social intelligence, and is consistent with other research indicating that the brain processes information about the social world differently from other types of information.

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J Pers Soc Psychol 2000 May;78(5):871-88

Just say no (to stereotyping): effects of training in the negation of stereotypic associations on stereotype activation.

Kawakami K, Dovidio JF, Moll J, Hermsen S, Russin A.

Department of Social Psychology, University of Nijmegen, The Netherlands. kawakami@pych.kun.nl

The primary aim of the present research was to examine the effect of training in negating stereotype associations on stereotype activation. Across 3 studies, participants received practice in negating stereotypes related to skinhead and racial categories. The subsequent automatic activation of stereotypes was measured using either a primed Stroop task (Studies I and 2) or a person categorization task (Study 3). The results demonstrate that when receiving no training or training in a nontarget category stereotype, participants exhibited spontaneous stereotype activation. After receiving an extensive amount of training related to a specific category, however, participants demonstrated reduced stereotype activation. The results from the training task provide further evidence for the impact of practice on participants' proficiency in negating stereotypes.
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Perception 1999;28(3):341-59

Evidence for holistic processing of faces viewed as photographic negatives.

Hole GJ, George PA, Dunsmore V.

School of Cognitive and Computing Sciences, University of Sussex, Falmer, Brighton, UK. grahamh@cogs.susx.ac.uk

Inversion and photographic negation both impair face recognition. Inversion seems to disrupt processing of the spatial relationship between facial features ('relational' processing) which normally occurs with upright faces and which facilitates their recognition. It remains unclear why negation affects recognition. To find out if negation impairs relational processing, we investigated whether negative faces are subject to the 'chimeric-face effect'. Recognition of the top half of a composite face (constructed from top and bottom halves of different faces) is difficult when the face is upright, but not when it is inverted. To perform this task successfully, the bottom half of the face has to be disregarded, but the relational processing which normally occurs with upright faces makes this difficult. Inversion reduces relational processing and thus facilitates performance on this particular task. In our experiments, subjects saw pairs of chimeric faces and had to decide whether or not the top halves were identical. On half the trials the two chimeras had identical tops; on the remaining trials the top halves were different. (The bottom halves were always different.) All permutations of orientation (upright or inverted) and luminance (normal or negative) were used. In experiment 1, each pair of 'identical' top halves were the same in all respects. Experiment 2 used differently oriented views of the same person, to preclude matches being based on incidental features of the images rather than the faces displayed within them. In both experiments, similar chimeric-face effects were obtained with both positive and negative faces, implying that negative faces evoke some form of relational processing. It is argued that there may be more than one kind of relational processing involved in face recognition: the 'chimeric-face effect' may reflect an initial 'holistic' processing which binds facial features into a 'Gestalt', rather than being a demonstration of the configurational processing involved in individual recognition.

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: J Exp Child Psychol 1999 Oct;74(2):69-106

Developmental sequences in class reasoning and propositional reasoning.

Muller U, Sokol B, Overton WF.

Temple University, Philadelphia, PA 19122, USA. Ulrich.Mueller@banyan.ummed.edu

This study explored the theoretical prediction that class and propositional reasoning skills emerge as a function of the developing ability to coordinate increasingly complex negation and affirmation operations. Children from Grades 1, 3, 5, and 7 (7-, 9-, 11-, and 13-year-olds) were presented with problems from each domain. Rasch analyses of the children's responses were consistent with the hypothesis that both types of problems measured a single underlying dimension (i.e., the coordination of affirmation and negation operations). Qualitatively distinct levels of class and propositional reasoning were identified along this dimension, adding support to the notion that children's reasoning follows a logical developmental sequence. Planned comparisons supported the order-theoretical prediction that different groups of items account for solution differences between grade levels. Results also indicated that children encounter significant difficulties when they have to reason on the basis of negative information. Copyright 1999 Academic Press.

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Cerebral Cortex, Vol. 9, No. 1, 65-76, January 1999
© 1999 Oxford University Press

The Functional Anatomy of the Normal Human Auditory System : Responses to 0.5 and 4.0 kHz Tones at Va
ried Intensities
Alan H. Lockwood1,2,5, Richard J. Salvi2,5,6, Mary Lou Coad1,4, Sally A. Arnold2, David S. Wack1,4, B. W. Murphy1,4 and Robert F. Burkard2,5,6

"...Cingulate activity was maximal at low stimulus intensities, suggesting that it may function as a gain control center. In the right temporal lobe, the location of the maximal response varied with the intensity, but not with the frequency of the stimuli. In the left temporal lobe, there was evidence for tonotopic organization: a site lateral to the left primary auditory cortex was activated equally by both tones while a second site in primary auditory cortex was more responsive to the higher frequency."
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J Exp Psychol Learn Mem Cogn 2002 Mar;28(2):303-17

The effect of negation on deductive inferences.

Lea RB, Mulligan EJ.

Department of Psychology, Macalester College, Saint Paul, Minnesota 55105, USA. lea@macalester.edu

Research shows that negation can suppress the activation of propositions presented explicitly in text, but does negation have a similar effect on propositions that can be inferred? That is, does negation inhibit the inference process? Four experiments investigated whether a deductive inference that produces a negated conclusion (therefore not a) is made as readily as a similar inference form that yields an affirmative conclusion (therefore a). A combination of naming latencies, verification times, and reading times indicate that negation does not affect the deductive inference process itself, although it may inhibit the activation of inferred concepts.
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Br J Psychol 2000 Nov;91 ( Pt 4):533-50

The effect of explicit negatives and of different contrast classes on conditional syllogisms.

Schaeken W, Schroyens W.

Laboratory of Experimental Psychology, University of Leuven, Belgium. walter.schaeken@psy.kuleuven.ac.be

One experiment tested the effects of systematically negating the constituents of four fundamental inferences based on conditionals: Modus Ponens (i.e. inferences of the form: if p then q; p therefore q), Modus Tollens (if p then q; not-q therefore not-p); Affirmation of the Consequent (if p then q; q therefore p), and Denial of the Antecedent (if p then q; not-p therefore not-q). The latter two inferences are valid only for bi-conditionals (if, and only if, p then q). The participants drew their own conclusions from premises about letters and numbers on cards. We observed a significant effect of explicit negatives on Modus Tollens and Denial of the Antecedent problems: The inferences were drawn more often for conditionals that yield a negative conclusion (e.g. if p then not q; q therefore not p) than for conditionals that yield an affirmative conclusion (e.g. if not p then q; not q therefore p). Additionally, we observed a similar, but smaller effect on Affirmation of the Consequent problems. Furthermore, we observed a significant effect of the categorical premise (affirmative or negative), especially on Affirmation of the Consequent problems. Finally, we observed an effect of the magnitude of the contrast class. If the contrast is larger (a set of three, five or nine values), then the making of a double negation or the production of an affirmative conclusion is more difficult for Denial of the Antecedent inferences. We discussed the results in relation to a negative categorical premise bias, an affirmative premise bias, a negative conclusion bias and a double negation effect.

Shinrigaku Kenkyu 2001 Jun;72(2):87-94

[Effects of negative-sentence suggestions on various behavior]

[Article in Japanese]

Miyashita T, Monzen S.

School of Human Sciences, Waseda University, Mikajima, Tokorozawa 359-1192.

The purpose of this study was to examine the effects of negative-sentence suggestions on various behavior. From the standpoint of the logic of negation, Miyashita (1998a, 1999) investigated the characteristics of feelings, sensations, and behavior. The results suggested that negative-sentence suggestions had more affirmative effects on mono-dimensional behavior than on multi-dimensional behavior. The present study examined this hypothesis. A total of 36 subjects (18 males, 18 females, mean age = 23.22, SD = 3.41) participated in the experiment. Subjects were given suggestions related to either mono-dimensional behavior or multi-dimensional behavior in negative-sentence form. An example of a suggestion related to mono-dimensional behavior would be "Your body does not move backwards", while an example for multi-dimensional behavior would be "Your body does not move." Body sway was then measured. Results showed that negative-sentence suggestions had more affirmative effects on mono-dimensional behavior than on multi-dimensional behavior. The hypothesis proposed by previous studies was supported.

Acta Paediatr 2000 Jul;89(7):830-5

Associations between cerebral blood-flow measured by single photon emission computed tomography (SPECT), electro-encephalogram (EEG), behaviour symptoms, cognition and neurological soft signs in children with attention-deficit hyperactivity disorder (ADHD).

Gustafsson P, Thernlund G, Ryding E, Rosen I, Cederblad M.

Department of Child and Adolescent Psychiatry, University Hospital, Malmo, Sweden.

Twenty-eight children with attention-deficit hyperactivity disorder (ADHD) were examined with SPECT (single photon emission computed tomography). Seven of the children had abnormal distribution of the regional cerebral blood-flow (rCBF) on visual evaluation and 10 had abnormal EEG findings. The only clinical finding that differentiated the group with normal from abnormal rCBF was behaviour symptom load. A factor analysis of the rCBF in different regions of interest yielded one factor with low rCBF in the temporal and cerebellar regions and high rCBF in the subcortical and thalamic regions, which was significantly associated with the degree of motor impairment and results on a cognitive test (WISC). Another factor consisting of high rCBF in frontal and parietal regions had a significant negative correlation with the degree of behaviour symptoms. There was a negative correlation between the rCBF in the right frontal regions and the degree of behaviour symptoms. The number of minor physical anomalies (MPA) was negatively correlated to the rCBF in the frontal lobes bilaterally. These results suggest that there may be at least two functional disturbances in ADHD, one specific neurodevelopmentally determined disturbance of the frontal lobes, especially of the right hemisphere, related to behaviour deviance, and another disturbance of the integration of the temporal lobes, the cerebellum and subcortical structures, related to motor planning and aspects of cognition.
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Audiol Neurootol 2000 May-Aug;5(3-4):225-34

Unilateral neglect after right-hemisphere damage: contributions from event-related potentials.

Deouell LY, Hamalainen H, Bentin S.

Department of Psychology, The Hebrew University of Jerusalem, Israel. msleon@mscc.huji.ac.il

Unilateral neglect is a frequent sequel of right-hemisphere damage. Patients suffering from neglect may fail to detect, orient to, acknowledge or respond to stimuli on their contralesional side, even in the absence of primary sensory or motor loss. Despite the major clinical significance of the phenomenon and its potential implications for our understanding of human cognition, the underlying cognitive deficits are not well understood. We review the relatively few event-related potential studies that attempted to assess the different parts of the cognitive system in neglect patients. We suggest that theories of neglect, based primarily on performance data, may be refined by incorporating these results, and that this line of research may provide information that is not available using traditional performance measures. Copyright 2000 S. Karger AG, Basel

Acta Neurobiol Exp (Warsz) 2000;60(1):17-28

Categorization of unilaterally presented emotional words: an ERP analysis.

Schapkin SA, Gusev AN, Kuhl J.

Institute of Psychology, Russian Academy of Sciences, Moscow, Russia. schapkin@psychol.ras.ru

This study is intended to clarify the functional role of different ERP components as indicators of the processing of emotions. The effect of emotional connotation of words on hemispheric lateralization is also explored. Visual ERPs were recorded to unilaterally presented positive, negative, and neutral words that should be categorized according to their emotional connotation. The P2 amplitude was larger to positive than to negative words whereas P3 amplitude was larger to positive words compared with neutral ones. The slow positive wave (SPW) was influenced by words emotionality at anterior and posterior sites differently. The amplitude of the N1 component was larger in the left hemisphere to contralaterally presented words. The P2 and P3 components were larger over the left hemisphere whereas the N3 and N4 components were larger over the right hemisphere to ipsilateral stimulation. The results support our hypotheses on the functional role of positive ERP components in the processing of an affective words connotation: the P2 wave reflects a general evaluation of emotional significance, the P3 a task-related decision, and the SPW an additional decision control in the context of the emotional experience of an individual. Neither the "right hemisphere hypothesis" nor "valence hypothesis" on lateralization of the processing of emotions were confirmed. Each hemisphere seems to exert its effect on emotion through specific hemispheric resources that are unequally allocated along the different stages of task processing and may cause alternation of hemispheric dominance.

J Clin Psychol 2001 Jul;57(7):901-14

Suicidal ideation and help-negation: Not just hopelessness or prior help.

Deane FP, Wilson CJ, Ciarrochi J.

Department of Psychology, University of Wollongong, Wollongong, NSW 2522, Australia. Frank_Deane@uow.edu.au

Few distressed young people seek professional psychological help and little is known about what sources of help young people seek for different problems. In suicidal youth, the process of help-negation may exacerbate poor help-seeking. Three hundred and two undergraduate university students completed a questionnaire measuring suicidal ideation, hopelessness, prior help-seeking experience, and help-seeking intentions. Participants indicated they would seek help from different sources of help for different types of problems, but friends consistently were rated as the most likely source of help. Help-negation was suggested by higher levels of suicidal ideation being associated with lower help-seeking intentions. However, the negative suicidal ideation/help-seeking-intentions relationship was not explained by hopelessness or prior help-seeking. Help-negation appears to involve more than just negative expectations regarding the future. The discussion proposes social problem-solving orientation as one of a number of potential explanatory variables. Copyright 2001 John Wiley & Sons, Inc.

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Cerebral Cortex, Vol. 11, No. 10, 954-965, October 2001
© 2001 Oxford University Press

New Evidence for Distinct Right and Left Brain Systems for Deductive versus Probabilistic Reasoning
Lawrence M. Parsons and Daniel Osherson1
University of Texas Health Science Center at San Antonio, San Antonio, TX and
1 Rice University, Houston, TX, USA

Lawrence M. Parsons, Director, Cognitive Neuroscience Program, Division of Behavioral and Cognitive Sciences, Directorate for Social, Behavioral, and Economic Sciences, National Science Foundation, 4201 Wilson Boulevard, Arlington, VA 22230, USA.

Deductive and probabilistic reasoning are central to cognition but the functional neuroanatomy underlying them is poorly understood. The present study contrasted these two kinds of reasoning via positron emission tomography. Relying on changes in instruction and psychological ‘set’, deductive versus probabilistic reasoning was induced using identical stimuli. The stimuli were arguments in propositional calculus not readily solved via mental diagrams. Probabilistic reasoning activated mostly left brain areas whereas deductive activated mostly right. Deduction activated areas near right brain homologues of left language areas in middle temporal lobe, inferior frontal cortex and basal ganglia, as well as right amygdala, but not spatial–visual areas. Right hemisphere activations in the deduction task cannot be explained by spill-over from overtaxed, left language areas. Probabilistic reasoning was mostly associated with left hemispheric areas in inferior frontal, posterior cingulate, parahippocampal, medial temporal, and superior and medial prefrontal cortices. The foregoing regions are implicated in recalling and evaluating a range of world knowledge, operations required during probabilistic thought. The findings confirm that deduction and induction are distinct processes, consistent with psychological theories enforcing their partial separation. The results also suggest that, except for statement decoding, deduction is largely independent of language, and that some forms of logical thinking are non-diagrammatic.

Oaksford, M., and Chater, N., (2001) "The probabilistic approach to human reasoning" IN Trends in Cognitive Sciences Vol 5. No8 August 2001: 349-357

"In a standard reasoning task, performance is compared with the inferences people should make according to logic, so a judgement can be made on the rationality of people's reasoning. It has been found that people make large and systematic (i.e. non-random) errors, which suggests that humans might be irrational. However, the probabilistic approach argues against this interpretation" (p349)

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Cerebral Cortex, Vol. 10, No. 5, 512-528, May 2000
© 2000 Oxford University Press

Human Temporal Lobe Activation by Speech and Nonspeech Sounds
J.R. Binder, J.A. Frost, T.A. Hammeke, P.S.F. Bellgowan, J.A. Springer, J.N. Kaufman and E.T. Possing
Department of Neurology and Department of Cellular Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA

Functional organization of the lateral temporal cortex in humans is not well understood. We recorded blood oxygenation signals from the temporal lobes of normal volunteers using functional magnetic resonance imaging during stimulation with unstructured noise, frequency-modulated (FM) tones, reversed speech, pseudowords and words. For all conditions, subjects performed a material- nonspecific detection response when a train of stimuli began or ceased. Dorsal areas surrounding Heschl's gyrus bilaterally, particularly the planum temporale and dorsolateral superior temporal gyrus, were more strongly activated by FM tones than by noise, suggesting a role in processing simple temporally encoded auditory information. Distinct from these dorsolateral areas, regions centered in the superior temporal sulcus bilaterally were more activated by speech stimuli than by FM tones. Identical results were obtained in this region using words, pseudowords and reversed speech, suggesting that the speech–tones activation difference is due to acoustic rather than linguistic factors. In contrast, previous comparisons between word and nonword speech sounds showed left-lateralized activation differences in more ventral temporal and temporoparietal regions that are likely involved in processing lexical–semantic or syntactic information associated with words. The results indicate functional subdivision of the human lateral temporal cortex and provide a preliminary framework for understanding the cortical processing of speech sounds.
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Cerebral Cortex, Vol. 11, No. 1, 17-25, January 2001
© 2001 Oxford University Press

Hemispheric and Gender-related Differences in the Gross Morphology of the Anterior Cingulate/Paracingulate Cortex in Normal Volunteers: An MRI Morphometric Study
Murat Yücel1,2,3, Geoffrey W. Stuart1,3, Paul Maruff1,2, Dennis Velakoulis1,3, Simon F. Crowe2, Greg Savage3 and Christos Pantelis1,3
1 Applied Schizophrenia Division, Mental Health Research Institute, Parkville, Victoria, Australia 3052,
2 School of Psychological Sciences, La Trobe University, Bundoora, Victoria, Australia 3083 and
3 Cognitive Neuropsychiatry Unit, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia 3052

The sulci and gyri found within the anterior cingulate (AC), and across the cerebrum generally, have been found to vary in location and complexity from one individual to the next, making it difficult to analyze imaging data accurately and systematically. In this study, we examined the nature of morphometric variance in the AC of the left and right cerebral hemispheres using high-resolution structural magnetic resonance imaging (MRI) acquired from 176 healthy volunteers. Depending on the presence of a paracingulate sulcus (PCS) and its antero-posterior extent, three types of AC patterns were identified: ‘prominent’, ‘present’ and ‘absent’. Hemispheric comparisons across the whole sample showed the PCS to be more commonly ‘prominent’ in the left hemisphere and more commonly ‘absent’ in the right hemisphere. There was a significant gender difference, such that males showed an asymmetric pattern characterized by increased fissurization of the left AC, while females showed greater symmetry, with less fissurization of the left AC. Overall cerebral morphology, namely hemispheric volume and hemispheric fissurization, were also measured and used as independent variables as well as covariates in the analyses in order to ascertain the specificity of the results regarding AC morphology. Results showed that cerebral volume for males was larger on the right than on the left while fissurization showed the reverse asymmetry of greater leftward fissurization. In contrast, females were symmetric in both respects. The findings regarding AC morphology could not be explained by differences in these overall cerebral measures or by differences in age and handedness within the population. The results suggest that in the normal male brain, there exist morphological asymmetries at both the global and local levels that are less apparent in the female brain. The findings have implications for future studies examining the organization, development and functional anatomy of the AC.
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Presse Med 2001 Feb 24;30(7):339-40

[Depression in the elderly. Clinical aspects]

[Article in French]

Barbier D.

Secteur 84.G.02, Centre Hospitalier de Montfavet, 2, avenue de la Pinede, BP 92, F 84128 Montfavet.

DIFFICULT DIAGNOSIS: Depression in the elderly can take on many often misleading aspects. Sadness may be considered legitimate or "normal" for an elderly person. Depression may masquerade as an organic disorder where somatic complaints, pain and anxiety predominate. All these different clinical forms may mislead the clinician. THE MASK OF HYPOCHONDRIA: A tendency to hypochondria, found in more than one-half of all depressed elderly subjects, may be reinforced by bouts of complementary examinations. The patient is convinced of having an unrecognized organic disease. The mask of hypochondria must be considered with special care because it is a major risk factor for attempted and successful suicide. THE MASK OF DELUSIONS: Elderly patients often develop a state of melancolia-like depression with delusions. Delusions may be congruent with the predominant depressed mood, for example a guilt feeling for an act never committed, or inversely, non-congruent with the thymic state (persecution, negation delusin), for example Cotard syndrome where the patient is persuaded that his/her organs are malfunctioning or have disappeared. Despite these impressive mood disorders that often incite prescription of a neuroleptic, these elderly patients respond favorably to antidepressor treatment.

Neurosci Lett 2000 Nov 17;294(2):89-92

The hemispherical laterality of the visual evoked potentials during simple dot stimulus in normal human subjects.

Omoto S, Kuroiwa Y, Li M, Kamitani T.

Department of Ophthalmology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, 236-0004, Yokohama, Japan.

We studied scalp visual evoked potentials (VEPs) during a simple visual attention paradigm using a dot stimulus, which was presented every 1600 ms, at the center of a screen. The visual attention paradigm consisted of three tasks: task R, task L and task N. The subjects were instructed to press a button either with the right hand (task R) or with the left hand (task L) after seeing the dot. They were also instructed just to look at a dot, without pressing the button (task N). We defined N1 as a negative wave with a latency of 50-130 ms, P1 as a positive wave with a latency of 110-150 ms and N2 as a negative wave with a latency of 130-210 ms. During task R, P1-N2 amplitude at T6 was significantly greater than that at T5. The N1-P1 and N2 amplitudes at O2 were significantly greater than those at O1. During task L, the waveforms at T6 and O2 were more clearly detected than those at T5 and O1. We conclude that there is a functional dominance of the right cerebral hemisphere in our simple visual reaction tasks.
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Schizophr Bull 2000;26(3):709-21

Altered hemispheric functional dominance during word generation in negative schizophrenia.

Artiges E, Martinot JL, Verdys M, Attar-Levy D, Mazoyer B, Tzourio N, Giraud MJ, Paillere-Martinot ML.

Functional brain imaging studies have reported decreased frontal activations in schizophrenia, but hemispheric dominance for language has rarely been assessed. To investigate regional activation and lateralization during word production, we determined normalized regional cerebral blood flow (rCBF) variations with positron emission tomography (PET) and H2(15)O (water labeled with the isotope oxygen 15) in 14 negative schizophrenia patients and 14 volunteers. Subjects were scanned during two trials of three conditions: rest, vocalized verbal fluency, and spontaneous word production. Images were analyzed using an anatomical volumes of interest method, and the two groups' changes were compared, using rest as a baseline. Differences in the lateralization of changes were detected in homologous frontal and inferior parietal regions. The lateralization effects in patients arose from lower activations in the left frontal regions, abnormal right inferior frontal activations, and weaker right inferior parietal deactivation, during the word production tasks. The right hemisphere changes correlated negatively with the performance in verbal fluency. Thus in negative schizophrenia patients, while the activations were less focused on the left hemisphere regions usually engaged in word generation, rCBF changes in the right hemisphere might reflect a compensatory functional pattern.

Shinrigaku Kenkyu 2000 Oct;71(4):325-30

[Configural and component processings in face recognition: comparison between inversion and negation effects]

[Article in Japanese]

Tsujii T, Itoh Y.

Division of Human Relations, Graduate School of Keio University, Mita, Minato-ku, Tokyo 108-8345.

It has previously been reported that subjects show difficulties in recognizing faces which are either inverted or in photographic negative. This study examined whether inversion and negation would disrupt the same aspects of face recognition processes in a same-different decision task for simultaneously presented faces. In a "different" condition, two faces were subtlely changed either in component information (eye size) or configural information (placement of inner features). The results revealed that negation equally disrupted component and configural processings, whereas inversion selectively disrupted configural processing more than component processing. Thus, the negation effect, which has been accounted for in terms of edge vs. surface processing, cannot be accounted for in terms of component vs. configural processing. It is concluded that inversion and negation selectively disrupt different aspects of cognitive processes underlying face recognition.

Brain Lang 1998 Feb 15;61(3):376-94

Presupposition and implication of truth: linguistic deficits following early brain lesions.

Eisele JA, Lust B, Aram DM.

Department of Pediatrics, Albany Medical College, NY 12208-3478, USA.

Twenty-four children (4-17 years) with unilateral left (N = 14) or right (N = 10) hemisphere damage and 24 age-matched controls were tested on their ability to presuppose the truth of factive sentences e.g., "Max knew that he locked the door," and to infer the truth or falsity of implicative sentences "Max remembered to lock the door." Experimental sentence types varied according to the type of inference, the semantic features of the verb (factive vs. implicative), the presence and type of negation (lexical or syntactic), and the syntax of the complement (tensed or infinitive). Relative to age-matched controls, left lesion subjects were deficient in both their presupposition and implication performance, particularly when such inferences required the computation of negation scope. Right lesion subjects exhibited a somewhat more selective deficit; one limited to implication, but not presupposition, and one limited to lexical but not syntactic forms of negation.

Mem Cognit 1997 Nov;25(6):888-909

Conceptual combination: conjunction and negation of natural concepts.

Hampton JA.

Psychology Department, City University, London, England. j.a.hampton@city.ac.uk

The operation of negation on combinations of natural categories was examined in two experiments. In the first, category membership ratings of lists of items were obtained for pairs of concepts considered individually and in two logical combinations: conjunctions (e.g., "Tools which are also Weapons") and negated conjunctions--forms of those conjunctions in which the modifier noun category was negated ("Tools which are not Weapons"). For conjunctions, results supported earlier findings of overextension and the geometric averaging of constituent membership values (Hampton, 1988b). Previous findings of concept dominance and noncommutativity within conjunctions were also replicated, both for typicality ratings and for probability of class membership. For negated conjunctions, the pattern of dominance was similar but interacted with order within the conjunction. Negated conjunctions were also overextended. The second experiment explored how the attributes of negated conjunctions were derived from those of the two component concepts. Frequency of generation of attributes expressed positively (has wheels) or negatively (has no wheels) followed rated frequency in the negated category. The distinctiveness of an attribute to distinguish the complement from the head-noun class was associated with the generation of attributes, particularly when there was relatively high overlap between the two categories.

J Int Neuropsychol Soc 1995 Nov;1(6):554-60

Right hemisphere mediation of verbal learning and memory in acquired right hemisphere speech dominant patients.

Sass KJ, Silberfein CM, Platis I, Westerveld M, Buchanan CP, Delaney RC, Kim JH, Spencer DD.

Department of Surgery (Neurosurgery), Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Forty-eight patients with temporal lobe epilepsy completed measures of narrative recall and list learning prior to surgery. The intracarotid amytal procedure (IAP) established that 13 patients were right hemisphere dominant for speech and 35 (18 left foci, 17 right foci) were left hemisphere dominant. Hippocampal volumetric neuron densities were measured after surgery. The left hippocampal neuron densities in subfields CA3 and the hilar area were significantly correlated with list learning ability and percent retention for narrative recall only for left hemisphere speech dominant patients with left seizure foci. No significant correlations between measures of neuron volume and memory were found for the left hemisphere speech dominant patients with right seizure foci or the right hemisphere speech dominant patients with left seizure foci. This suggests that the right hemisphere of right speech dominant patients mediates verbal memory as well as speech. This conclusion is supported by patterns of correlations among measures of verbal memory that differed for patients undergoing resection of the dominant hemisphere versus those undergoing resection of the nondominant hemisphere. However, it is premature to conclude that the cerebral organization of cognitive functions of right hemisphere speech dominant patients is equivalent albeit reversed from that of left hemisphere speech dominant patients. Right hemisphere speech dominant patients with left temporal foci differed from left hemisphere speech dominant patients with right temporal foci with respect to the patterns of correlations between measures of verbal memory and intelligence as well as the level of intellectual ability that they demonstrated.

(IDM : right brained superpositions?)

J Neurol Neurosurg Psychiatry 1995 Jul;59(1):50-4

Cerebral and callosal organisation in a right hemisphere dominant "split brain" patient.

Lutsep HL, Wessinger CM, Gazzaniga MS.

Center for Neuroscience, University of California Davis 95616, USA.

Patients described in previous reports who have undergone corpus callostomy for control of seizures have been left hemisphere dominant for language. To determine the hemispheric localisation (and possible coexistence) of language and traditional right hemisphere skills in reversed dominance, the first right hemisphere dominant corpus callostomy patient was studied. Localisation of callosal functions was also investigated, as MRI showed 1.5 cm of spared callosal body. The patient, KO, a 15 year old girl with familial left handedness, underwent two stage callosotomy in 1988. Lateralised visually presented stimuli requiring same or different comparisons between visual fields showed chance performance. Oral naming and reading showed better performance by the right hemisphere than the left, whereas both hemispheres were proficient in auditory comprehension. Active voice syntax was above chance only in the right hemisphere. Face recognition was significantly better in the right hemisphere than in the left. Tasks requiring tactile comparisons between hands showed above chance performance except in the instance in which the non-dominant right hand was stimulated first in a point localisation task between hands. This case showed hemispheric coexistence of language and traditional right hemispheric skills in a corpus callosotomy patient with reversed language dominance. Tactile transfer was localised to the mid-posterior callosal body.

J Child Neurol 1995 Jul;10(4):310-4

Right-hemisphere dysfunction in Asperger's syndrome.

McKelvey JR, Lambert R, Mottron L, Shevell MI.

Department of Neurology/Neurosurgery, McGill University, Montreal, Quebec, Canada.

Asperger's syndrome has many clinical features in common with acquired right-hemisphere dysfunction and has been postulated to result from a developmental abnormality of the right hemisphere. However, right-hemisphere abnormality has not previously been documented on neuroanatomic or functional imaging in patients with Asperger's syndrome. We report three patients with Asperger's syndrome found to have abnormal right-hemisphere function on single photon emission computed tomographic (SPECT) imaging. The subjects were two males and one female, ranging from 12 to 16 years of age. All were diagnosed on the basis of the presence of the complete constellation of clinical features previously outlined. All patients were investigated with computed tomographic (CT) scanning, magnetic resonance imaging (MRI), and SPECT scanning. In one subject, CT and MRI revealed enlargement of the right lateral ventricle, reflecting a mild degree of right hemispheric atrophy. CT and MRI studies on the other two subjects were normal. SPECT scanning demonstrated right hemispheric abnormalities in each subject: right temporal hypoperfusion with a central area of increased perfusion along with frontal polar hyperperfusion in one; diffusely decreased right hemispheric uptake in the second; and decreased frontal and occipital uptake in the third. Cerebellar abnormalities were also present: a smaller right hemisphere with increased uptake in the first; decreased uptake in the vermis and right hemisphere in the second; and decreased vermal uptake in the third. These findings support the hypothesis that the neurobiologic basis of Asperger's syndrome is a developmental abnormality of the right cerebral hemisphere.

Semin Pediatr Neurol 1997 Jun;4(2):70-6

Normal language acquisition.

Rescorla L, Mirak J.

Department of Psychology, Bryn Mawr College, PA 19010, USA.

Long before they start talking, children are skilled at using eye contact, facial expression, and nonverbal gestures to communicate with other people. They also are able to discriminate speech sounds from an early age. Vocabulary learning builds on the child's knowledge about objects, actions, locations, properties, and stages gained as a result of sensorimotor development. Early word combinations allow children to express semantic relationships between these various referents. During the period from 2 to 4 years of age, children move from expressing their ideas in simple telegraphic speech to being able to ask questions, use negation, talk about past and future events, and describe complicated situations using sentences constructed according to complex grammatical rules.

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Cerebral Cortex, Vol. 9, No. 4, 379-391, June 1999
© 1999 Oxford University Press

The Functional Neuroanatomy of Novelty Processing: Integrating ERP and fMRI Results
B. Opitz, A. Mecklinger, A.D. Friederici and D.Y. von Cramon
Max-Planck-Institute of Cognitive Neuroscience, Leipzig, Germany

Recent research indicates that non-tonal novel events, deviating from an ongoing auditory environment, elicit a positive event-related potential (ERP), the novel P3. Although a variety of studies examined the neural network engaged in novelty detection, there is no complete picture of the underlying brain mechanisms. This experiment investigated these neural mechanisms by combining ERP and functional magnetic resonance imaging (fMRI). Hemodynamic and electrophysiological responses were measured in the same subjects using the same experimental design. The ERP analysis revealed a novel P3, while the fMRI responses showed bilateral foci in the middle part of the superior temporal gyrus. When subjects attended to the novel stimuli only identifiable novel sounds evoked a N4-like negativity. Subjects showing a strong N4-effect had additional fMRI activation in right prefrontal cortex (rPFC) as compared to subjects with a weak N4-effect. This pattern of results suggests that novelty processing not only includes the registration of deviancy but may also lead to a fast access and retrieval of related semantic concepts. The fMRI activation pattern suggests that the superior temporal gyrus is involved in novelty detection, whereas accessing and retrieving semantic concepts related to novel sounds additionally engages the rPFC.
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Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 17, 11447-11451, August 20, 2002

Neurobiology
Dissociable prefrontal brain systems for attention and emotion
(novelty|prefrontal cortex|amygdala|cingulate gyrus)

Hiroshi Yamasaki*,, Kevin S. LaBar, and Gregory McCarthy*,§,¶
* Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC 27710; Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki 444-0806, Japan; Center for Cognitive Neuroscience, Duke University, Durham, NC 27708; and § Department of Veterans Affairs Medical Center, Durham, NC 27705

Edited by Patricia S. Goldman-Rakic, Yale University School of Medicine, New Haven, CT, and approved July 10, 2002 (received for review March 26, 2002)

The prefrontal cortex has been implicated in a variety of attentional, executive, and mnemonic mental operations, yet its functional organization is still highly debated. The present study used functional MRI to determine whether attentional and emotional functions are segregated into dissociable prefrontal networks in the human brain. Subjects discriminated infrequent and irregularly presented attentional targets (circles) from frequent standards (squares) while novel distracting scenes, parametrically varied for emotional arousal, were intermittently presented. Targets differentially activated middle frontal gyrus, posterior parietal cortex, and posterior cingulate gyrus. Novel distracters activated inferior frontal gyrus, amygdala, and fusiform gyrus, with significantly stronger activation evoked by the emotional scenes. The anterior cingulate gyrus was the only brain region with equivalent responses to attentional and emotional stimuli. These results show that attentional and emotional functions are segregated into parallel dorsal and ventral streams that extend into prefrontal cortex and are integrated in the anterior cingulate. These findings may have implications for understanding the neural dynamics underlying emotional distractibility on attentional tasks in affective disorders.
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Am J Psychiatry 158:938-943, June 2001
© 2001 American Psychiatric Association

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Article

A Functional Magnetic Resonance Imaging Study of Auditory Mismatch in Schizophrenia
Cynthia G. Wible, Ph.D., Marek Kubicki, M.D., Ph.D., Seung-Schik Yoo, Ph.D., Daniel F. Kacher, M.S., Dean F. Salisbury, Ph.D., Mark C. Anderson, M.S., Martha E. Shenton, Ph.D., Yoshio Hirayasu, M.D., Ph.D., Ron Kikinis, M.D., Ferenc A. Jolesz, M.D., and Robert W. McCarley, M.D.
OBJECTIVE: Previous research has noted functional and structural temporal lobe abnormalities in schizophrenia that relate to symptoms such as auditory hallucinations and thought disorder. The goal of the study was to determine whether the functional abnormalities are present in schizophrenia at early stages of auditory processing. METHOD: Functional magnetic resonance imaging activity was examined during the presentation of the mismatch stimuli, which are deviant tones embedded in a series of standard tones. The mismatch stimuli are used to elicit the mismatch negativity, an early auditory event-related potential. Ten patients with schizophrenia and 10 comparison subjects were presented the mismatch stimuli condition and a control condition in which only one tone was presented repeatedly. RESULTS: The superior temporal gyrus showed the most prevalent and consistent activation. The superior temporal gyrus showed less activation in the schizophrenic subjects than in the comparison subjects only during the mismatch stimuli condition. CONCLUSIONS: This result is consistent with those of mismatch negativity event-related potential studies and suggests that early auditory processing is abnormal in chronic schizophrenia.
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Cerebral Cortex, Vol. 11, No. 3, 267-277, March 2001
© 2001 Oxford University Press

Conjoint and Extended Neural Networks for the Computation of Speech Codes: The Neural Basis of Selective Impairment in Reading Words and Pseudowords
Benjamin Xu, Jordan Grafman1, William D. Gaillard2, Kenji Ishii, Francisco Vega-Bermudez, Pietro Pietrini1, Patricia Reeves-Tyer, Paul DiCamillo and William Theodore
Epilepsy Research Branch and
1 Cognitive Neuroscience Section, NINDS, the National Institutes of Health, Bethesda, MD 20892 and
2 The Department of Neurology, Children's National Medical Center, Washington, DC, USA

The computation of speech codes (i.e. phonology) is an important aspect of word reading. Understanding the neural systems and mech- anisms underlying phonological processes provides a foundation for the investigation of language in the brain. We used high-resolution three-dimensional positron emission tomography (PET) to investigate neural systems essential for phonological processes. The burden of neural activities on the computation of speech codes was maximized by three rhyming tasks (rhyming words, pseudowords and words printed in mixed letter cases). Brain activation patterns associated with these tasks were compared with those of two baseline tasks involving visual feature detection. Results suggest strong left lateralized epicenters of neural activity in rhyming irrespective of gender. Word rhyming activated the same brain regions engaged in pseudoword rhyming, suggesting conjoint neural networks for phonological processing of words and pseudowords. However, pseudoword rhyming induced the largest change in cerebral blood flow and activated more voxels in the left posterior prefrontal regions and the left inferior occipital–temporal junction. In addition, pseudoword rhyming activated the left supramarginal gyrus, which was not apparent in word rhyming. These results suggest that rhyming pseudowords requires active participation of extended neural systems and networks not observed for rhyming words. The implications of the results on theories and models of visual word reading and on selective reading dysfunctions after brain lesions are discussed.
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Cerebral Cortex, Vol. 9, No. 2, 137-150, March 1999
© 1999 Oxford University Press

Synchronization Between Temporal and Parietal Cortex During Multimodal Object Processing in Man
A. von Stein1,2,3, P. Rappelsberger1, J. Sarnthein1,3 and H. Petsche1

1 Institut für Neurophysiologie, Universität Wien, Währingerstrasse17, A-1090 Vienna and
2 Konrad Lorenz Institut für Evolutions- and Kognitionsforschung, A-3422 Altenberg, Austria

A series of recordings in cat visual cortex suggest that synchronous activity in neuronal cell ensembles serves to bind the different perceptual qualities belonging to one object. We provide evidence that similar mechanisms seem also to be observable in human subjects for the representation of supramodal entities. Electroencephalogram (EEG) was recorded from 19 scalp electrodes (10/20 system) in 19 human subjects and EEG amplitude and coherence were determined during presentation of objects such as house, tree, ball. Objects were presented in three different ways: in a pictorial presentation, as spoken words and as written words. In order to find correlates of modality-independent processing, we searched for patterns of activation common to all three modalities of presentation. The common pattern turned out to be an increase of coherence between temporal and parietal electrodes in the 13–18 Hz beta1 frequency range. This is evidence that population activity of temporal cortex and parietal cortex shows enhanced coherence during presentation of semantic entities. Coherent activity in this low-frequency range might play a role for binding of multimodal ensembles.
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The Journal of Neuroscience, June 1, 2001, 21(11):3942-3948

Transient Interhemispheric Neuronal Synchrony Correlates with Object Recognition
Tatsuya Mima, Tomi Oluwatimilehin, Taizo Hiraoka, and Mark Hallett
Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1428

Object recognition might be achieved by the recreation of a meaningful internal image from visual fragments. This recreation might be achieved by neuronal synchronization that has been proposed as a solution for the perceptual binding problem. In this study, we evaluated synchronization between the occipitotemporal regions bilaterally using electroencephalograms during several visual recognition tasks. Conscious recognition of familiar objects spanning the visual midline induced transient interhemispheric electroencephalographic coherence in the band, which did not occur with meaningless objects or with passive viewing. Moreover, there was no interhemispheric coherence when midline objects were not recognized as meaningful or when familiar objects were presented in one visual hemifield. These data suggest a close link between site-specific interregional synchronization and object recognition.

Key words: object recognition; neuronal synchronization; EEG; interhemispheric coherence; perceptual binding; visual recognition task
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Vol. 97, Issue 4, 1867-1872, February 15, 2000

Neurobiology
Gamma rhythms and beta rhythms have different synchronization properties
N. Kopell,, G. B. Ermentrout§, M. A. Whittington¶, and R. D. Traub
Department of Mathematics and Center for BioDynamics, Boston University, Boston MA 02215; § Department of Mathematics, University of Pittsburgh, Pittsburgh PA 15260; ¶ School of Biomedical Sciences, Worsley Building, University of Leeds, Leeds LS2 9NL, United Kingdom; and Division of Neuroscience, The Medical School, University of Birmingham, Birmingham B15 2TT, United Kingdom

Contributed by Nancy J. Kopell, December 3, 1999

Experimental and modeling efforts suggest that rhythms in the CA1 region of the hippocampus that are in the beta range (12-29 Hz) have a different dynamical structure than that of gamma (30-70 Hz). We use a simplified model to show that the different rhythms employ different dynamical mechanisms to synchronize, based on different ionic currents. The beta frequency is able to synchronize over long conduction delays (corresponding to signals traveling a significant distance in the brain) that apparently cannot be tolerated by gamma rhythms. The synchronization properties are consistent with data suggesting that gamma rhythms are used for relatively local computations whereas beta rhythms are used for higher level interactions involving more distant structures.
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Cerebral Cortex, Vol. 11, No. 1, 37-58, January 2001
© 2001 Oxford University Press

A Neural Model of how Horizontal and Interlaminar Connections of Visual Cortex Develop into Adult Circuits that Carry Out Perceptual Grouping and Learning
Stephen Grossberg and James R. Williamson
Department of Cognitive and Neural Systems and Center for Adaptive Systems, Boston University, Boston, MA 02215, USA

A neural model suggests how horizontal and interlaminar connections in visual cortical areas V1 and V2 develop within a laminar cortical architecture and give rise to adult visual percepts. The model suggests how mechanisms that control cortical development in the infant lead to properties of adult cortical anatomy, neurophysiology and visual perception. The model clarifies how excitatory and inhibitory connections can develop stably by maintaining a balance between excitation and inhibition. The growth of long-range excitatory horizontal connections between layer 2/3 pyramidal cells is balanced against that of short-range disynaptic interneuronal connections. The growth of excitatory on-center connections from layer 6-to-4 is balanced against that of inhibitory interneuronal off-surround connections. These balanced connections interact via intracortical and intercortical feedback to realize properties of perceptual grouping, attention and perceptual learning in the adult, and help to explain the observed variability in the number and temporal distribution of spikes emitted by cortical neurons. The model replicates cortical point spread functions and psychophysical data on the strength of real and illusory contours. The on-center, off-surround layer 6-to-4 circuit enables top-down attentional signals from area V2 to modulate, or attentionally prime, layer 4 cells in area V1 without fully activating them. This modulatory circuit also enables adult perceptual learning within cortical area V1 and V2 to proceed in a stable way.
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Cerebral Cortex, Vol. 12, No. 10, 1048-1056, October 2002
© 2002 Oxford University Press

Brain Activity Underlying Encoding and Retrieval of Source Memory
Selene Cansino, Pierre Maquet1,2, Raymond J. Dolan2 and Michael D. Rugg3
Laboratory of NeuroCognition, Faculty of Psychology, National Autonomous University of Mexico, Mexico City, Mexico,
1 Cyclotron Research Center, University of Liege, Liege, Belgium,
2 Wellcome Department of Cognitive Neurology, Institute of Neurology and
3 Institute of Cognitive Neuroscience and Department of Psychology, University College London, UK

Address correspondence to Selene Cansino, Laboratory of Neuro-Cognition, Faculty of Psychology, National Autonomous University of Mexico, Apartado Postal 25-308, Mexico DF, 03421 Mexico. Email: selene@servidor.unam.mx.

Neural activity elicited during the encoding and retrieval of source information was investigated with event-related functional magnetic resonance imaging (efMRI). During encoding, 17 subjects performed a natural/artificial judgement on pictures of common objects which were presented randomly in one of the four quadrants of the display. At retrieval, old pictures were mixed with new ones and subjects judged whether each picture was new or old and, if old, indicated in which quadrant it was presented at encoding. During encoding, study items that were later recognized and assigned a correct source judgement elicited greater activity than recognized items given incorrect judgements in a variety of regions, including right lateral occipital and left prefrontal cortex. At retrieval, regions showing greater activity for recognized items given correct versus incorrect source judgements included the right hippocampal formation and the left prefrontal cortex. These findings indicate a role for these regions in the encoding and retrieval of episodic information beyond that required for simple item recognition.
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Cerebral Cortex, Vol. 11, No. 10, 966-974, October 2001
© 2001 Oxford University Press

The Priming Method: Imaging Unconscious Repetition Priming Reveals an Abstract Representation of Number in the Parietal Lobes
Lionel Naccache and Stanislas Dehaene
Unité INSERM 334, Service Hospitalier Frédéric Joliot, CEA/DRM/DSV, 4 Place du Général Leclerc, F-91401 Orsay Cedex, France

Lionel Naccache, Unité INSERM 334, Service Hospitalier Frédéric Joliot, CEA/DRM/DSV, 4 Place du Général Leclerc, 91401 Orsay Cedex, France. Email: naccache@shfj.cea.fr

Most of the current brain imaging methods are limited by the low spatial resolution of neuroimaging techniques and remain unable to measure activity at the scale of single neurons or small columns of neurons, which are the coding elements of the nervous system. In this work we have adapted the priming method, an emerging research strategy that can overcome some of these spatial limitations, to investigate the coding of numerical quantities in the human brain. This approach combines the logic of psychological priming experiments with the recently discovered neurophysiological phenomenon called repetition suppression (RS). In each trial, while subjects perform a constant task, a subliminal prime is presented prior to each target. By varying the relationship between prime and target, one can detect which brain areas present RS specifically for any given level of prime–target repetition. We first expose the general logic, potential and limitations of the priming method and then illustrate it by demonstrating that a region of parietal cortex is coding for numbers at the quantity level, independently of other stimulus attributes, and that this region processes both consciously and unconsciously perceived stimuli.
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Cerebral Cortex, Vol. 9, No. 3, 213-221, April 1999
© 1999 Oxford University Press

From Perception to Action: Temporal Integrative Functions of Prefrontal and Parietal Neurons
Javier Quintana and Joaquin M. Fuster
Department of Psychiatry and Biobehavioral Sciences and Brain Research Institute, School of Medicine, University of California at Los Angeles, Los Angeles, CA 90024-1759, USA

The dorsolateral prefrontal cortex (DPFC) and the posterior parietal cortex (PPC) are anatomically and functionally interconnected, and have been implicated in working memory and the preparation for behavioral action. To substantiate those functions at the neuronal level, we designed a visuomotor task that dissociated the perceptual and executive aspects of the perception–action cycle in both space and time. In that task, the trial-initiating cue (a color) indicated with different degrees of certainty the direction of the correct manual response 12 s later. We recorded extracellular activity from 258 prefrontal and 223 parietal units in two monkeys performing the task. In the DPFC, some units (memory cells) were attuned to the color of the cue, independent of the response-direction it connoted. Their discharge tended to diminish in the course of the delay between cue and response. In contrast, few color-related units were found in PPC, and these did not show decreasing patterns of delay activity. Other units in both cortices (set cells) were attuned to response-direction and tended to accelerate their firing in anticipation of the response and in proportion to the predictability of its direction. A third group of units was related to the determinacy of the act; their firing was attuned to the certainty with which the animal could predict the correct response, whatever its direction. Cells of the three types were found closely intermingled histologically. These findings further support and define the role of DPFC in executive functions and in the temporal closure of the perception– action cycle. The findings also agree with the involvement of PPC in spatial aspects of visuomotor behavior, and add a temporal integrative dimension to that involvement. Together, the results provide physiological evidence for the role of a prefrontal–parietal network in the integration of perception with action across time.
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Cerebral Cortex, Vol. 9, No. 5, 497-506, July 1999
© 1999 Oxford University Press

Nouns and Verbs in the Intact Brain: Evidence from Event-related Potentials and High-frequency Cortical Responses
Friedemann Pulvermüller, Werner Lutzenberger1 and Hubert Preissl1
Department of Psychology, Universität Konstanz, 78457 Konstanz and
1 Institut für Medizinische Psychologie, Universität Tübingen, 72074 Tübingen, Germany

Lesion evidence indicates that words from different lexical categories, such as nouns and verbs, may have different cortical counterparts. In this study, processing of nouns and verbs was investigated in the intact brain using (i) behavioral measures, (ii) stimulus-triggered event-related potentials and (iii) high-frequency electrocortical responses in the gamma band. Nouns and verbs carefully matched for various variables, including word frequency, length, arousal and valence, were presented in a lexical decision task while electrocortical responses were recorded. In addition, information about cognitive processing of these stimuli was obtained using questionnaires and reaction times. As soon as ~200 ms after stimulus onset, event-related potentials disclosed electrocortical differences between nouns and verbs over widespread cortical areas. In a later time window, 500–800 ms after stimulus onset, there was a significant difference between high-frequency responses in the 30 Hz range. Difference maps obtained from both event-related potentials and high-frequency responses revealed strong betweencategory differences of signals recorded above motor and visual cortices. Behavioral data suggest that these different physiological responses are related to semantic associations (motor or visual) elicited by these word groups. Our results are consistent with a neurobiological model of language representation postulating cell assemblies with distinct cortical topographies as biological counterparts of words. Assemblies representing nouns referring to visually perceived objects may include neurons in visual cortices, and assemblies representing action verbs may include additional neurons in motor, premotor and prefrontal cortices. Event-related potentials and high-frequency responses are proposed to indicate two different functional states of cell assemblies: initial full activation (`ignition') and continuous reverberatory activity.
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(Journal of Cognitive Neuroscience. 2002;14:561-577.)
© 2002 The MIT Press

Neural Differentiation of Lexico-Syntactic Categories or Semantic Features?
Event-Related Potential Evidence for Both
Marion L. Kellenbach, Albertus A. Wijers, Marjolijn Hovius, Juul Mulder and Gijsbertus Mulder
University of Groningen

Event-related potentials (ERPs) were used to investigate whether processing differences between nouns and verbs can be accounted for by the differential salience of visual-perceptual and motor attributes in their semantic specifications. Three subclasses of nouns and verbs were selected, which differed in their semantic attribute composition (abstract, high visual, high visual and motor). Single visual word presentation with a recognition memory task was used. While multiple robust and parallel ERP effects were observed for both grammatical class and attribute type, there were no interactions between these. This pattern of effects provides support for lexical–semantic knowledge being organized in a manner that takes account both of category-based (grammatical class) and attribute-based distinctions.
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Cerebral Cortex, Vol. 12, No. 2, 212-221, February 2002
© 2002 Oxford University Press

Dynamics of Gamma-band Activity Induced by Auditory Pattern Changes in Humans
Jochen Kaiser1, Werner Lutzenberger1, Hermann Ackermann2 and Niels Birbaumer1,3
1 MEG Center, Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, 72074 Tübingen, Germany,
2 Department of Neurology, University of Tübingen, 72076 Tübingen, Germany and
3 Department of Psychology, University of Padova, 35131 Padova, Italy

Dr Jochen Kaiser, Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Gartenstrasse 29, 72074 Tübingen, Germany. Email: jochen.kaiser@unituebingen.de.

Increasing evidence suggests separate auditory pattern and space processing streams. The present paper describes two magnetoencephalogram studies examining gamma-band activity to changes in auditory patterns using consonant–vowel syllables (experiment 1), animal vocalizations and artificial noises (experiment 2). Two samples of each sound type were presented to passively listening subjects in separate oddball paradigms with 80% standards and 20% deviants differing in their spectral composition. Evoked magnetic mismatch fields peaking ~190 ms poststimulus showed a trend for a left-hemisphere advantage for syllables, but no hemispheric differences for the other sounds. Frequency analysis and statistical probability mapping of the differences between deviants and standards revealed increased gamma-band activity above 60 Hz over left anterior temporal/ventrolateral prefrontal cortex for all three types of stimuli. This activity peaked simultaneously with the mismatch responses for animal sounds (180 ms) but was delayed for noises (260 ms) and syllables (320 ms). Our results support the hypothesized role of anterior temporal/ventral prefrontal regions in the processing of auditory pattern change. They extend earlier findings of gamma-band activity over posterior parieto-temporal cortex during auditory spatial processing that supported the putative auditory dorsal stream. Furthermore, earlier gamma-band responses to animal vocalizations may suggest faster processing of fear-relevant information.
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Neurocase (2001) Vol. 7, pp. 303-317
© Oxford University Press 2001

The Right Hemisphere's Role in Action Word Processing: a Double Case Study
Bettina Neininger1,2 and Friedemann Pulvermüller1,2,3
1 Department of Psychology, University of Konstanz, PO Box D25, 78457 Konstanz, 2 Lurija Institut, Kliniken Schmieder Allensbach, Postfach 240, 78473 Allensbach, Germany and 3 Cognition and Brain Sciences Unit, Medical Research Council,15 Chaucer Road, Cambridge CB2 2EF, UK

Correspondence to: Bettina Neininger, Department of Psychology, University of Konstanz, PO Box D25, 78457 Konstanz, Germany. Tel: +49 (0)7531 88 3086; Fax: +49 (0)7531 88 2891; e-mail: bettina.neininger@uni-konstanz.de

Word category-specific deficits were investigated in two patients with right hemispheric lesions and hemiparesis affecting the left extremities. Words from three categories, action verbs, nouns with strong visual associations and nouns with both strong action and visual associations, were presented in a lexical decision task. The stimulus categories were matched for word length and frequency. In both patients, responses to action verbs were slowed and/or less accurate compared with the other word categories. This was so even in the patient with a minor lesion in the motor, pre-motor and somatosensory areas of the hand representation. Control subjects did not show category differences when tested with the same stimulus materials. These results are consistent with the view that the cortical areas involved in the programming of body movements, even those in the hemisphere not dominant for language, specifically contribute to and are necessary for the processing of words referring to such movements. As an alternative, the affected brain areas may be of particular relevance for the processing of words from the lexical category of verbs. The results are consistent with a brain model of language based on Hebb's cell assembly concept.
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Brain, Vol. 123, No. 12, 2552-2566, December 2000
© 2000 Oxford University Press

Brain responses to nouns, verbs and class-ambiguous words in context
Kara D. Federmeier1, Jessica B. Segal3, Tania Lombrozo4 and Marta Kutas1,2
1 Departments of Cognitive Science and 2 Neurosciences, University of California San Diego, La Jolla, California, 3 Department of Neurology, Johns Hopkins University, Baltimore, Maryland and 4 Stanford University, Stanford, California, USA

Correspondence to: Kara D. Federmeier, Department of Cognitive Science, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0515, USA E-mail: kfederme@cogsci.ucsd.edu

Recent neuropsychological and imaging data have implicated different brain networks in the processing of different word classes, nouns being linked primarily to posterior, visual object-processing regions and verbs to frontal, motor-processing areas. However, as most of these studies have examined words in isolation, the consequences of such anatomically based representational differences, if any, for the processing of these items in sentences remains unclear. Additionally, in some languages many words (e.g. `drink') are class-ambiguous, i.e. they can play either role depending on context, and it is not yet known how the brain stores and uses information associated with such lexical items in context. We examined these issues by recording event-related potentials (ERPs) in response to unambiguous nouns (e.g. `beer'), unambiguous verbs (e.g. `eat'), class-ambiguous words and pseudowords used as nouns or verbs within two types of minimally contrastive sentence contexts: noun-predicting (e.g. `John wanted THE [target] but ...') and verb-predicting (`John wanted TO [target] but ...'). Our results indicate that the nature of neural processing for nouns and verbs is a function of both the type of stimulus and the role it is playing. Even when the context completely specifies their role, word class-ambiguous items differ from unambiguous ones over frontal regions by ~150 ms. Moreover, whereas pseudowords elicit larger N400s when used as verbs than when used as nouns, unambiguous nouns and ambiguous words used as nouns elicit more frontocentral negativity than unambiguous verbs and ambiguous words used as verbs, respectively. Additionally, unambiguous verbs elicit a left-lateralized, anterior positivity (~200 ms) not observed for any other stimulus type, though only when these items are used appropriately as verbs (i.e. in verb-predicting contexts). In summary, the pattern of neural activity observed in response to lexical items depends on their general probability of being a verb or a noun and on the particular role they are playing in any given sentence. This implicates more than a simple two-way distinction of the brain networks involved in their storage and processing. Experience, as well as context during on-line language processing, clearly shapes the neural representations of nouns and verbs, such that there is no single neural marker of word class. Our results further suggest that the presence and nature of the word class-based dissociations observed after brain damage are similarly likely to be a function of both the type of stimulus and the context in which it occurs, and thus must be assessed accordingly.
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(Journal of Cognitive Neuroscience. 2001;13:713-720.)
© 2001 The MIT Press

Grammatical Distinctions in the Left Frontal Cortex
Kevin A. Shapiro
Harvard University

Alvaro Pascual-Leone, Felix M. Mottaghy and Massimo Gangitano

Harvard Medical School/Beth Israel-Deaconess Medical Center

Alfonso Caramazza

Harvard University

Selective deficits in producing verbs relative to nouns in speech are well documented in neuropsychology and have been associated with left hemisphere frontal cortical lesions resulting from stroke and other neurological disorders. The basis for these impairments is unresolved: Do they arise because of differences in the way grammatical categories of words are organized in the brain, or because of differences in the neural representation of actions and objects? We used repetitive transcranial magnetic stimulation (rTMS) to suppress the excitability of a portion of left prefrontal cortex and to assess its role in producing nouns and verbs. In one experiment subjects generated real words; in a second, they produced pseudowords as nouns or verbs. In both experiments, response latencies increased for verbs but were unaffected for nouns following rTMS. These results demonstrate that grammatical categories have a neuroanatomical basis and that the left prefrontal cortex is selectively engaged in processing verbs as grammatical objects.
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*************************** inhibit = habits, integrate, excite = differentiate *******************
Cerebral Cortex, Vol. 12, No. 6, 575-584, June 2002
© 2002 Oxford University Press

Inhibitory and Excitatory Responses of Single Neurons in the Human Medial Temporal Lobe during Recognition of Faces and Objects
Itzhak Fried1,2,3, Katherine A. Cameron1, Sharona Yashar1, Raymond Fong1 and Jack W. Morrow1
1 Division of Neurosurgery and
2 Department of Psychiatry & Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, CA 90095, USA and
3 Functional Neurosurgery Unit, Tel-Aviv Medical Center and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Itzhak Fried, Division of Neurosurgery, Box 957039, UCLA School of Medicine, Los Angeles, CA 90095-7039, USA. Email: ifried@mednet.ucla.edu.

The medial temporal lobe (MTL) plays a critical role in transforming complex stimuli into permanent memory traces, yet little is known on how the activity of neurons in the human brain mediates this process. Recording from single neurons in the human MTL during visual encoding and retrieval of faces and objects, we found that in the hippocampus faces evoked predominantly suppression of neuronal firing below prestimulus baseline (‘inhibitory responses’). These responses were also prevalent in the entorhinal cortex but were absent in the amygdala during the first second of stimulus encoding when all responses to faces were ‘excitatory’ (neuronal firing increased above the prestimulus baseline). Inhibitory responses were more prevalent during recognition than encoding and were also present during processing of objects, albeit less frequently than during processing of faces. Despite the prevalence in the hippocampus of cells with inhibitory responses and their relative specificity to faces, it was mainly the activity of the cells with excitatory responses that was selective for stimulus features such as gender and emotional expression of faces. These findings suggest that a large population of cells with inhibitory responses is engaged in the hippocampal memory network, but primarily cells with excitatory responses process feature-specific information.
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Cerebral Cortex, Vol. 12, No. 8, 818-830, August 2002
© 2002 Oxford University Press

Machine Psychology: Autonomous Behavior, Perceptual Categorization and Conditioning in a Brain-based Device
Jeffrey L. Krichmar and Gerald M. Edelman
W.M. Keck Laboratory, The Neurosciences Institute, 10640 John Jay Hopkins Drive, San Diego, CA 92121, USA

Jeffrey L. Krichmar, W.M. Keck Laboratory, The Neurosciences Institute, 10640 John Jay Hopkins Drive, San Diego, CA 92121, USA. Email: krichmar@nsi.edu.

In studying brain activity during the behavior of living animals, it is not possible simultaneously to analyze all levels of control from molecular events to motor responses. To provide insights into how levels of control interact, we have carried out synthetic neural modeling using a brain-based real-world device. We describe here the design and performance of such a device, designated Darwin VII, which is guided by computer-simulated analogues of cortical and subcortical structures. All levels of Darwin VII’s neural architecture can be examined simultaneously as the device behaves in a real environment. Analysis of its neural activity during perceptual categorization and conditioned behavior suggests neural mechanisms for invariant object recognition, experience-dependent perceptual categorization, first-order and second-order conditioning, and the effects of different learning rates on responses to appetitive and aversive events. While individual Darwin VII exemplars developed similar categorical responses that depended on exploration of the environment and sensorimotor adaptation, each showed highly individual patterns of changes in synaptic strengths. By allowing exhaustive analysis and manipulation of neuroanatomy and large-scale neural dynamics, such brain-based devices provide valuable heuristics for understanding cortical interactions. These devices also provide the groundwork for the development of intelligent machines that follow neurobiological rather than computational principles in their construction.
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Cerebral Cortex, Vol 6, 288-296, Copyright © 1996 by Oxford University Press

Deviant auditory stimuli activate human left and right auditory cortex differently
S Levanen, A Ahonen, R Hari, L McEvoy and M Sams
Low Temperature Laboratory, Helsinki University of Technology, Espoo, Finland.

Infrequent "deviant' auditory stimuli embedded in a homogeneous sequence of "standard' sounds evoke a neuromagnetic mismatch field (MMF), which is assumed to reflect automatic change detection in the brain. We investigated whether MMFs would reveal hemispheric differences in cortical auditory processing. Seven healthy adults were studied with a whole-scalp neuromagnetometer. The sound sequence, delivered to one ear at time, contained three infrequent deviants (differing from standards in duration, frequency, or interstimulus interval) intermixed with standard tones. MMFs peaked 9-34 msec earlier in the right than in the left hemisphere, irrespective of the stimulated ear. Whereas deviants activated only one MMF source in the left hemisphere, two temporally overlapping but spatially separate sources, one in the temporal lobe and another in the inferior parietal cortex, were necessary to explain the right-hemisphere MMFs. We suggest that the bilateral MMF components originating in the supratemporal cortex are feature specific whereas the right-hemisphere parietal component reflects more global auditory change detection. The results imply hemispheric differences in sound processing and suggest stronger involvement of the right than the left hemisphere in change detection.
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The Journal of Neuroscience, September 1, 2000, 20(17):6631-6639

Right-Hemisphere Dominance for the Processing of Sound-Source Lateralization
Jochen Kaiser1, Werner Lutzenberger1, Hubert Preissl1, Hermann Ackermann2, and Niels Birbaumer1, 3
1 Magnetoencephalography Center, Institute of Medical Psychology and Behavioral Neurobiology and 2 Department of Neurology, University of Tübingen, 72076 Tübingen, Germany, and 3 Department of Psychology, University of Padua, 35131 Padova, Italy

Cortical processing of change in direction of a perceived sound source was investigated in 12 human subjects using whole-head magnetoencephalography. The German word "da" was presented either with or without 0.7 msec interaural time delays to create the impression of right- or left-lateralized or midline sources, respectively. Midline stimuli served as standards, and lateralized stimuli served as deviants in a mismatch paradigm. Two symmetrically linked dipoles fitted to the mismatch fields showed stronger moments in the hemisphere contralateral to the side of the deviant. The right dipole displayed equal latencies to both left and right deviants, whereas left dipole latencies were longer for ipsilateral than contralateral deviants. Frequency analysis between 20-70 Hz and statistical probability mapping revealed increased induced gamma-band activity at 53 ± 2.5 Hz to both types of deviants. Right deviants elicited spectral amplitude enhancements in this frequency range, peaking at latencies of 160 and 240 msec. These effects were localized bilaterally over the angular gyri and posterior temporal regions. Coherence analysis suggested the existence of two separate interhemispheric networks. For left-lateralized deviants, both spectral amplitude enhancements at 110 and 220 msec and coherence increases were restricted to the right hemisphere. In conclusion, both mismatch dipole latencies at the supratemporal plane and gamma-band activity in posterior parietotemporal areas suggested a right hemisphere engagement in the processing of bidirectional sound-source shifts. In contrast, left-hemisphere regions responded predominantly to contralateral events. These findings may help to elucidate phenomena such as unilateral auditory neglect.

Key words: sound-source lateralization; magnetoencephalogram (MEG); mismatch response; dipole latency; gamma-band activity (GBA); coherence; posterior parietal cortex; auditory dorsal stream; human subjects
===============
PNAS Vol. 96, Issue 18, 10460-10465, August 31, 1999

Neurobiology
Native language, gender, and functional organization of the auditory cortex
R. Salmelin*,, A. Schnitzler, L. Parkkonen*, K. Biermann, P. Helenius*, K. Kiviniemi*, K. Kuukka*, F. Schmitz, and H.-J. Freund
* Brain Research Unit, Low Temperature Laboratory, Helsinki University of Technology, P.O. Box 2200, FIN-02015 HUT, Finland; and Department of Neurology, Heinrich Heine University, Moorenstrasse 5, D-40225 Düsseldorf, Germany

Communicated by Olli V. Lounasmaa, Helsinki University of Technology, Espoo, Finland, June 25, 1999 (received for review March 19, 1999)

Whole-head magnetoencephalography was employed in 40 normal subjects to investigate whether the basic functional organization of the auditory cortex varies with linguistic environment. Robust activations of the bilateral supratemporal auditory cortices to 1-kHz pure tones, maximum at about 100 ms after stimulus onset, were studied in Finnish and German female and male subject groups with monolingual background. Activations elicited by the tones were mutually indistinguishable in German and Finnish women. In contrast, German men showed significantly stronger auditory responses to pure tones in the left, language-dominant hemisphere than Finnish men. We discuss the possibility that the prominent left-hemisphere activation in German males reflects higher frequency resolution required for distinguishing between German than Finnish vowels and that the clear effect of native language in male but not in female auditory cortex derives from more pronounced functional lateralization in men. The present data suggest that the influence of native language can extend to auditory cortical processing of pure-tone stimuli with no linguistic content and that this effect is conspicuous in the male brain.
==============
The Journal of Neuroscience, September 1, 2000, 20(17):6631-6639

Right-Hemisphere Dominance for the Processing of Sound-Source Lateralization
Jochen Kaiser1, Werner Lutzenberger1, Hubert Preissl1, Hermann Ackermann2, and Niels Birbaumer1, 3
1 Magnetoencephalography Center, Institute of Medical Psychology and Behavioral Neurobiology and 2 Department of Neurology, University of Tübingen, 72076 Tübingen, Germany, and 3 Department of Psychology, University of Padua, 35131 Padova, Italy

Cortical processing of change in direction of a perceived sound source was investigated in 12 human subjects using whole-head magnetoencephalography. The German word "da" was presented either with or without 0.7 msec interaural time delays to create the impression of right- or left-lateralized or midline sources, respectively. Midline stimuli served as standards, and lateralized stimuli served as deviants in a mismatch paradigm. Two symmetrically linked dipoles fitted to the mismatch fields showed stronger moments in the hemisphere contralateral to the side of the deviant. The right dipole displayed equal latencies to both left and right deviants, whereas left dipole latencies were longer for ipsilateral than contralateral deviants. Frequency analysis between 20-70 Hz and statistical probability mapping revealed increased induced gamma-band activity at 53 ± 2.5 Hz to both types of deviants. Right deviants elicited spectral amplitude enhancements in this frequency range, peaking at latencies of 160 and 240 msec. These effects were localized bilaterally over the angular gyri and posterior temporal regions. Coherence analysis suggested the existence of two separate interhemispheric networks. For left-lateralized deviants, both spectral amplitude enhancements at 110 and 220 msec and coherence increases were restricted to the right hemisphere. In conclusion, both mismatch dipole latencies at the supratemporal plane and gamma-band activity in posterior parietotemporal areas suggested a right hemisphere engagement in the processing of bidirectional sound-source shifts. In contrast, left-hemisphere regions responded predominantly to contralateral events. These findings may help to elucidate phenomena such as unilateral auditory neglect.

Key words: sound-source lateralization; magnetoencephalogram (MEG); mismatch response; dipole latency; gamma-band activity (GBA); coherence; posterior parietal cortex; auditory dorsal stream; human subjects
==============
Journal of Neuroscience, Vol 1, 323-331, Copyright © 1981 by Society for Neuroscience

Variability in right hemisphere language function after callosal section: evidence for a continuum of generative capacity
JJ Sidtis, BT Volpe, DH Wilson, M Rayport and MS Gazzaniga

Two recent patients in our behavioral series investigating the psychological effects of callosal section exhibit right hemisphere language. Using lateralized visual and auditory stimulation, semantic, phonetic, and expressive linguistic functions were examined. While the right hemisphere language systems in both patients were shown to be capable of semantic information processing, they differed in their abilities to process phonetic information, follow verbal commands, and produce linguistic responses. It is argued that the differences between left and right hemisphere language systems are quantitative and are best characterized along a continuum of generative capacity. It is the variability in such capacity that appears to be responsible for the variability in right hemisphere language function within the split- brain population.
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Brain, Vol. 123, No. 7, 1293-1326, July 2000
© 2000 Oxford University Press

Cerebral specialization and interhemispheric communication
Does the corpus callosum enable the human condition?
Michael S. Gazzaniga
Center for Cognitive Neuroscience, Dartmouth College, Hanover, New Hampshire, USA

Correspondence to: Michael S. Gazzaniga, Center for Cognitive Neuroscience, Dartmouth College, Hanover, NH 03755, USA

The surgical disconnection of the cerebral hemispheres creates an extraordinary opportunity to study basic neurological mechanisms: the organization of the sensory and motors systems, the cortical representation of the perceptual and cognitive processes, the lateralization of function, and, perhaps most importantly, how the divided brain yields clues to the nature of conscious experience. Studies of split-brain patients over the last 40 years have resulted in numerous insights into the processes of perception, attention, memory, language and reasoning abilities. When the constellation of findings is considered as a whole, one sees the cortical arena as a patchwork of specialized processes. When this is considered in the light of new studies on the lateralization of functions, it becomes reasonable to suppose that the corpus callosum has enabled the development of the many specialized systems by allowing the reworking of existing cortical areas while preserving existing functions. Thus, while language emerged in the left hemisphere at the cost of pre-existing perceptual systems, the critical features of the bilaterally present perceptual system were spared in the opposite half-brain. By having the callosum serve as the great communication link between redundant systems, a pre-existing system could be jettisoned as new functions developed in one hemisphere, while the other hemisphere could continue to perform the previous functions for both half-brains. Split-brain studies have also revealed the complex mosaic of mental processes that participate in human cognition. And yet, even though each cerebral hemisphere has its own set of capacities, with the left hemisphere specialized for language and speech and major problem-solving capacities and the right hemisphere specialized for tasks such as facial recognition and attentional monitoring, we all have the subjective experience of feeling totally integrated. Indeed, even though many of these functions have an automatic quality to them and are carried out by the brain prior to our conscious awareness of them, our subjective belief and feeling is that we are in charge of our actions. These phenomena appear to be related to our left hemisphere's interpreter, a device that allows us to construct theories about the relationship between perceived events, actions and feelings.
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(Journal of Cognitive Neuroscience. 2002;14:702-708.)
© 2002 The MIT Press

Hemispheric Encoding Asymmetry is More Apparent Than Real
Michael B. Miller
University of Massachusetts Boston

Alan Kingstone

University of British Columbia

Michael S. Gazzaniga

Dartmouth College

Previous neuroimaging studies have claimed a left hemisphere specialization for episodic "encoding" and a right hemisphere specialization for episodic "retrieval." Yet studies of split-brain patients indicate relatively minor memory impairment after disconnection of the two hemispheres. This suggests that both hemispheres are capable of encoding and retrieval. In the present experiment, we examined the possible limits on encoding capacity of each hemisphere by manipulating the "depth" of processing during the encoding of unfamiliar faces and familiar words in the left and right hemispheres of two split-brain patients. Results showed that only the left hemisphere benefited from deeper (more elaborate) encoding of familiar words, and only the right hemisphere benefited from deeper encoding of unfamiliar faces. Our findings are consistent with the view that hemispheric asymmetries in episodic encoding are related to hemisphere-specific processing of particular stimuli. Convergent with recent neuroimaging studies, these results with split-brain patients also suggest that these hemispheric differences are not due to unique specializations in each half brain for encoding memories, but rather, are due to preferential recruitment of the synaptically closer prefrontal cortex to posterior regions processing material-specific information.
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Published online before print May 21, 2002, 10.1073/pnas.122644899;
Proc. Natl. Acad. Sci. USA, Vol. 99, Issue 11, 7803-7808, May 28, 2002

Psychology-BS
Hemispheric asymmetry in human lateral prefrontal cortex during cognitive set shifting
Seiki Konishi*,, Toshihiro Hayashi*, Idai Uchida*, Hideyuki Kikyo*, Emi Takahashi*, and Yasushi Miyashita*,
* Department of Physiology, University of Tokyo School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan; and National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan

Edited by Brenda Milner, McGill University, Montreal, Canada, and approved April 8, 2002 (received for review December 4, 2001)

Functional organization of human cerebral hemispheres is asymmetrically specialized, most typically along a verbal/nonverbal axis. In this event-related functional MRI study, we report another example of the asymmetrical specialization. Set-shifting paradigms derived from the Wisconsin card sorting test were used, where subjects update one behavior to another on the basis of environmental feedback. The cognitive requirements constituting the paradigms were decomposed into two components according to temporal stages of task events. Double dissociation of the component brain activity was found in the three bilateral pairs of regions in the lateral frontal cortex, the right regions being activated during exposure to negative feedback and the corresponding left regions being activated during updating of behavior, to suggest that both hemispheres contribute to cognitive set shifting but in different ways. The asymmetrical hemispheric specialization within the same paradigms further implies an interhemispheric interaction of these task components that achieve a common goal.
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Journal of Neuroscience, Vol 15, 2748-2755, Copyright © 1995 by Society for Neuroscience

Magnetic and electric brain activity evoked by the processing of tone and vowel stimuli
C Eulitz, E Diesch, C Pantev, S Hampson and T Elbert
Institute for Experimental Audiology, University of Munster, Germany.

Sustained magnetic and electric brain waves may reflect linguistic processing when elicited by auditory speech stimuli. In the present study, only in the latency interval subsequent to the N1m/N1 has a sensitivity of brain responses to features of speech been demonstrated. We conclude this from studying the auditory-evoked magnetic field (AEF) and the corresponding evoked potential (AEP) in response to vowels and a tone. Brain activity was recorded from the left and the right hemisphere of 11 subjects. Three aspects of transient activity were examined: (1) the amplitudes and source characteristics of the N1m component of the AEF; (2) the amplitudes and source characteristics of the sustained field (SF), and (3) the corresponding amplitude characteristics of the AEP. Sustained potential amplitudes and SF root mean square amplitudes, as well as the dipole strength of the SF source, were found to be larger for vowel-evoked signals than for signals elicited by the tone stimulus. The amplitude and dipole strength effects had an interaction with hemisphere, with larger interhemispheric differences for the vowel condition, as well as larger tone-vowel differences of these parameters in the speech-dominant left hemisphere. No statistically significant hemisphere-by-stimulus-type interactions were found in N1/N1m amplitudes and N1m source parameters.
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Am J Psychiatry 1983; 140:1340-1344
Copyright © 1983 by American Psychiatric Association

Altered lateralization of cognitive processes in depressed women
EK Silberman, H Weingartner, R Stillman, HJ Chen and RM Post

Eighteen normal men and women had a left hemisphere advantage for processing a verbal task, but depressed women showed a trend toward right hemisphere superiority. In depression the right hemisphere may share functions performed exclusively by the left hemisphere in normal subjects. Altered laterality may be a trait of depression-prone people or a change related to depressive episodes themselves. In the latter case, the right hemisphere may be compensating for relative deactivation of the dominant left hemisphere.
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Am J Psychiatry 158:1437-1440, September 2001
© 2001 American Psychiatric Association

Perceptual Asymmetries in Schizophrenia: Subtype Differences in Left Hemisphere Dominance for Dichotic Fused Words
Michelle S. Friedman, M.A., Gerard E. Bruder, Ph.D., Paul G. Nestor, Ph.D., Barbara K. Stuart, B.A., Xavier F. Amador, Ph.D., and Jack M. Gorman, M.D.
OBJECTIVE: Dichotic listening techniques have been used to study hemispheric dominance for language in schizophrenia. The authors’ goal was to compare subjects with paranoid and undifferentiated subtypes of schizophrenia. METHOD: The Fused Rhymed Words Test was used to compare perceptual asymmetries in 16 patients with paranoid schizophrenia, 28 patients with undifferentiated schizophrenia, and 29 healthy comparison subjects. RESULTS: Patients with paranoid schizophrenia had the largest left hemisphere advantage and patients with undifferentiated schizophrenia had the smallest. The asymmetry of healthy subjects was intermediate. Hemisphere advantage varied as a function of gender only in the patients with undifferentiated schizophrenia. CONCLUSIONS: The findings support the hypotheses that undifferentiated schizophrenia is associated with underactivation of left hemisphere resources for verbal processing and that paranoid schizophrenia is characterized by preserved left hemisphere processing.
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Am J Psychiatry 1995; 152:932-935
Copyright © 1995 by American Psychiatric Association

Smaller right ear (left hemisphere) advantage for dichotic fused words in patients with schizophrenia
G Bruder, E Rabinowicz, J Towey, A Brown, CA Kaufmann, X Amador, D Malaspina and JM Gorman
Department of Biopsychology, New York State Psychiatric Institute, NY 10032, USA.

OBJECTIVE: The purposes of this study were to compare right ear (left hemisphere) advantage for dichotic words in schizophrenia and depression and to assess its association with antipsychotic medication, symptom ratings, and gender. METHOD: Thirty-two schizophrenic patients and 65 patients with major depression were given the Fused Rhymed Words Test, a dichotic listening measure of hemispheric dominance for language. RESULTS: An earlier finding of smaller left hemisphere advantage in schizophrenic patients was replicated. There was no significant change in ear advantage in a subgroup of the schizophrenic patients tested when they were taking neuroleptics and when they were not. The smaller left hemisphere advantage in the schizophrenic patients was not dependent on gender but was related to symptom ratings on the Positive and Negative Syndrome Scale. CONCLUSIONS: The findings are consistent with a left hemisphere dysfunction in schizophrenia, which is associated with positive symptoms.
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Am J Psychiatry 157:759-766, May 2000
© 2000 American Psychiatric Association

Central Auditory Processing in Patients With Auditory Hallucinations
Colette M. McKay, Ph.D., Donna M. Headlam, M.Sc., and David L. Copolov, M.B., Ph.D.
ABSTRACT

OBJECTIVE: Data from a full assessment of auditory perception in patients with schizophrenia were used to investigate whether auditory hallucinations are associated with abnormality of central auditory processing. METHOD: Three groups of subjects participated in auditory assessments: 22 patients with psychosis and a recent history of auditory hallucinations, 16 patients with psychosis but no history of auditory hallucinations, and 22 normal subjects. Nine auditory assessments, including auditory brainstem response, monotic and dichotic speech perception tests, and nonspeech perceptual tests, were performed. Statistical analyses for group differences were performed using analysis of variance and Kruskal-Wallis tests. The results of individual patients with test scores in the severely abnormal range (more than three standard deviations from the mean for the normal subjects) were examined for patterns that suggested sites of dysfunction in the central auditory system. RESULTS: The results showed significant individual variability among the subjects in both patient groups. There were no group differences on tests that are sensitive to low brainstem function. Both patient groups performed poorly in tests that are sensitive to cortical or high brainstem function, and hallucinating patients differed from nonhallucinating patients in scores on tests of filtered speech perception and response bias patterns on dichotic speech tests. Six patients in the hallucinating group had scores in the severely abnormal range on more than one test. CONCLUSIONS: Hallucinations may be associated with auditory dysfunction in the right hemisphere or in the interhemispheric pathways. However, comparison of results for the patient groups suggests that the deficits seen in hallucinating patients may represent a greater degree of the same types of deficits seen in nonhallucinating patients.
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Am J Psychiatry 157:1279-1284, August 2000
© 2000 American Psychiatric Association

Hypnotic Visual Illusion Alters Color Processing in the Brain
Stephen M. Kosslyn, Ph.D., William L. Thompson, B.A., Maria F. Costantini-Ferrando, Ph.D., Nathaniel M. Alpert, Ph.D., and David Spiegel, M.D.
OBJECTIVE: This study was designed to determine whether hypnosis can modulate color perception. Such evidence would provide insight into the nature of hypnosis and its underlying mechanisms. METHOD: Eight highly hypnotizable subjects were asked to see a color pattern in color, a similar gray-scale pattern in color, the color pattern as gray scale, and the gray-scale pattern as gray scale during positron emission tomography scanning by means of [15O]CO2. The classic color area in the fusiform or lingual region of the brain was first identified by analyzing the results when subjects were asked to perceive color as color versus when they were asked to perceive gray scale as gray scale. RESULTS: When subjects were hypnotized, color areas of the left and right hemispheres were activated when they were asked to perceive color, whether they were actually shown the color or the gray-scale stimulus. These brain regions had decreased activation when subjects were told to see gray scale, whether they were actually shown the color or gray-scale stimuli. These results were obtained only during hypnosis in the left hemisphere, whereas blood flow changes reflected instructions to perceive color versus gray scale in the right hemisphere, whether or not subjects had been hypnotized. CONCLUSIONS: Among highly hypnotizable subjects, observed changes in subjective experience achieved during hypnosis were reflected by changes in brain function similar to those that occur in perception. These findings support the claim that hypnosis is a psychological state with distinct neural correlates and is not just the result of adopting a role.
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(Journal of Cognitive Neuroscience. 2002;14:887-901.)
© 2002 The MIT Press

Hypnosis Modulates Activity in Brain Structures Involved in the Regulation of Consciousness
Pierre Rainville
Université de Montréal

Robert K. Hofbauer and M. Catherine Bushnell

McGill University

Gary H. Duncan

Université de Montréal

Donald D. Price

University of Florida

The notion of consciousness is at the core of an ongoing debate on the existence and nature of hypnotic states. Previously, we have described changes in brain activity associated with hypnosis (Rainville, Hofbauer, Paus, Duncan, Bushnell, & Price, 1999). Here, we replicate and extend those findings using positron emission tomography (PET) in 10 normal volunteers. Immediately after each of 8 PET scans performed before (4 scans) and after (4 scans) the induction of hypnosis, subjects rated their perceived level of "mental relaxation" and "mental absorption," two of the key dimensions describing the experience of being hypnotized. Regression analyses between regional cerebral blood flow (rCBF) and self-ratings confirm the hypothesized involvement of the anterior cingulate cortex (ACC), the thalamus, and the ponto-mesencephalic brainstem in the production of hypnotic states. Hypnotic relaxation further involved an increase in occipital rCBF that is consistent with our previous interpretation that hypnotic states are characterized by a decrease in cortical arousal and a reduction in cross-modality suppression (disinhibition). In contrast, increases in mental absorption during hypnosis were associated with rCBF increases in a distributed network of cortical and subcortical structures previously described as the brain's attentional system. These findings are discussed in support of a state theory of hypnosis in which the basic changes in phenomenal experience produced by hypnotic induction reflect, at least in part, the modulation of activity within brain areas critically involved in the regulation of consciousness.
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Am J Psychiatry 1997; 154:812-818
Copyright © 1997 by American Psychiatric Association

Size, shape, and orientation of neurons in the left and right hippocampus: investigation of normal asymmetries and alterations in schizophrenia
DW Zaidel, MM Esiri and PJ Harrison
Department of Psychology, University of California at Los Angeles 90095- 1563, USA.

OBJECTIVE: Schizophrenia may involve the two cerebral hemispheres differentially. This study was conducted to determine whether left and right hippocampal neuronal size, shape, and orientation are normally asymmetrical or asymmetrically affected in schizophrenia. METHOD: The authors examined postmortem tissue from the left and right hippocampus of 17 normal individuals and 14 individuals with schizophrenia. They measured the size, shape, and variability in orientation of pyramidal neurons in hippocampal subfields CA1-CA4 and the subiculum in computer images of 10-micron coronal sections stained with cresyl violet. RESULTS: Both neuronal size and shape showed significant effects of diagnosis and a three-way interaction between diagnosis, hemisphere, and subfield. Neurons of the schizophrenic subjects were smaller than those of the normal subjects in the left CA1, left CA2, and right CA3 subfields; their shape differed from that of the normal subjects in the left CA1, left subiculum, and right CA3 subfields. There were no group differences in variability of neuronal orientation, but neurons in the CA3 genu in the schizophrenic subjects were less variable on the right than on the left. In the normal subjects, except for larger neurons in the left than in the right CA2 subfield and some left-right differences in variability of neuronal orientation, no statistically significant asymmetries were observed. CONCLUSIONS: The data confirm that hippocampal neuronal size is decreased in schizophrenia and reveal that the shape of neurons is altered, supporting the view that hippocampal cytoarchitectural abnormalities may be part of the cerebral substrate of schizophrenia. They also provide further evidence that the abnormalities are localized and lateralized.
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Am J Psychiatry 1988; 145:944-949
Copyright © 1988 by American Psychiatric Association

Patterns of thought disorder associated with right cortical damage, schizophrenia, and mania
EK Daniels, ME Shenton, PS Holzman, LI Benowitz, M Coleman, S Levin and D Levine
Mailman Research Center, McLean Hospital, Belmont, Mass.

The authors used the Thought Disorder Index to measure thought disorder in 23 patients with unilateral right hemisphere cortical damage, 20 patients with bipolar mania, and 25 patients with schizophrenia. There were no differences in the total amount of thought disorder in these groups, but each showed a unique pattern of thought disorder. Patients with right hemisphere damage displayed fragmented thinking, manic patients displayed playful thinking, and schizophrenic patients displayed idiosyncratic thinking. These findings support the view that thought disorder is manifested in different forms that are relatively specific to psychiatric or neurological condition.
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Am J Psychiatry 156:1159-1163, August 1999
© 1999 American Psychiatric Association

Bipolar Disorder: Anomalous Brain Asymmetry Associated With Psychosis
Martin Reite, M.D., Peter Teale, M.S.E.E., Donald C. Rojas, Ph.D., David Arciniegas, M.D., and Jeanelle Sheeder, B.A.
OBJECTIVE: Anomalous cerebral asymmetry in schizophreniform disorders has been described, but its presence in psychotic mood disorders has not been established. Measures of cerebral asymmetry may distinguish patients with psychotic mood disorders from those with nonpsychotic mood disorders and from comparison subjects. To test this hypothesis, the authors examined functional cerebral asymmetry by using a metric based on magnetic source imaging. METHOD: A total of 33 subjects participated. Nine were patients with bipolar I disorder and a negative history of psychotic symptoms during mood disorder episodes, 12 were patients with bipolar I disorder and a positive history of psychotic symptoms during mood disorder episodes, and 12 were nonpsychiatric comparison subjects. Equivalent current dipole generators in both hemispheres were estimated for the 20-msec-latency somatosensory evoked field (M20) component produced by stimulation of the contralateral median nerve. RESULTS: The comparison subjects demonstrated asymmetry in anterior-posterior equivalent current dipole locations of the M20 (right anterior to left), and the bipolar subjects with no history of psychosis were similarly asymmetric. The bipolar subjects with a history of psychosis during mood episodes, however, demonstrated a reversal of cerebral asymmetry of the M20 (left anterior to right). CONCLUSIONS: Cerebral lateralization of the M20 distinguished bipolar subjects with psychosis from those without psychosis and comparison subjects. The M20 is generated in area 3b of the postcentral gyrus. These findings suggest anatomical displacement of the postcentral gyrus in psychotic disorders and support the hypothesis that anomalous cerebral asymmetry is a feature of psychotic disorders generally, including psychotic mood disorders.
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Annu. Rev. Neurosci. 2002. 25:151-188.

FUNCTIONAL MRI OF LANGUAGE: New Approaches to Understanding the Cortical Organization of Semantic Processing
Susan Bookheimer
Brain Mapping Center, UCLA School of Medicine, Los Angeles, California 90095; email: sbook@ucla.edu

KEY WORDS: fMRI, functional neuroimaging, inferior frontal gyrus, speech, comprehension, semantics

Until recently, our understanding of how language is organized in the brain depended on analysis of behavioral deficits in patients with fortuitously placed lesions. The availability of functional magnetic resonance imaging (fMRI) for in vivo analysis of the normal brain has revolutionized the study of language. This review discusses three lines of fMRI research into how the semantic system is organized in the adult brain. These are (a) the role of the left inferior frontal lobe in semantic processing and dissociations from other frontal lobe language functions, (b) the organization of categories of objects and concepts in the temporal lobe, and (c) the role of the right hemisphere in comprehending contextual and figurative meaning. Together, these lines of research broaden our understanding of how the brain stores, retrieves, and makes sense of semantic information, and they challenge some commonly held notions of functional modularity in the language system.
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The British Journal of Psychiatry 167: 783-785 (1995)
© 1995 The Royal College of Psychiatrists

Month of birth, hemisphere of birth and schizophrenia
J McGrath, J Welham and M Pemberton
Clinical Studies Unit, Wolston Park Hospital, Brisbane, Australia.

BACKGROUND: To assess quarterly fluctuations in schizophrenia births in a southern hemisphere data set, and to compare the quarterly birth distributions of patients born in the northern and southern hemisphere. METHOD: The month and place of birth of patients with schizophrenia (n = 9348) were extracted from a mental health register. RESULTS: The quarterly birth distribution of patients with schizophrenia differed significantly from the estimated general population distribution in SH- born patients. The quarterly distribution of patient births differed significantly when the two hemispheres were compared. CONCLUSION: These data support the hypothesis that there is a risk for schizophrenia that is related to the time of birth, and which fluctuates across the year.
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Brain Res Mol Brain Res 2002 Nov 15;107(2):183-189

Schizophrenia and Nogo: elevated mRNA in cortex, and high prevalence of a homozygous CAA insert.

Novak G, Kim D, Seeman P, Tallerico T.

Department of Pharmacology, Medical Sciences Building, University of Toronto, Room 4344, Medical Science Building, 8 Taddle Creek Road, Ontario, M5S 1A8, Toronto, Canada

Schizophrenia is a major psychiatric disorder which is hypothesized to result from abnormal neurodevelopment or neural changes in adulthood and possibly associated with altered gene expression. To search for genes overexpressed in schizophrenia, cDNA library subtractive hybridization experiments between post-mortem human frontal cerebral cortices from schizophrenia individuals and neurological controls were carried out. One of the genes over-expressed in schizophrenia was identified as Nogo (also known as reticulon 4, RTN4, NI 250, or RTN-X), a myelin-associated protein which inhibits the outgrowth of neurites and nerve terminals. The elevated expression of Nogo mRNA in schizophrenia was confirmed by quantitative reverse transcription-polymerase chain reaction studies: 16.5 pg Nogo cDNA/&mgr;g total RNA in schizophrenia, and 10.2 pg Nogo cDNA/&mgr;g total RNA in controls (n=7; P=0.01, t-test for n<30). To identify possible polymorphisms in this gene, the Nogo nucleotide sequence was determined in a series of schizophrenia and control samples. The Nogo mRNA was found to contain a CAA insert polymorphism in the 3'-untranslated region. The prevalence of individuals homozygous for this CAA insert was significantly higher in schizophrenia compared to controls in genomic DNA samples extracted from post-mortem brain and blood samples: 17/81 or 21% in schizophrenia and 2/61 or 3% in controls (P=0.0022, chi(2)- and Fisher's exact-tests). Because the 3'-untranslated regions of eukaryotic genes are known to regulate gene expression, the increased frequency of the Nogo CAA insert in schizophrenia may contribute to abnormal regulation of Nogo gene expression, and may indicate a role for Nogo in disturbed neurodevelopment in schizophrenia.

Published online before print February 20, 2001, 10.1073/pnas.041431898;
Proc. Natl. Acad. Sci. USA, Vol. 98, Issue 5, 2934-2939, February 27, 2001

Social Sciences
Lifespan depends on month of birth
Gabriele Doblhammer* and James W. Vaupel
Max Planck Institute for Demographic Research, Doberanerstrasse 114, 18057 Rostock, Germany

Edited by Kenneth W. Wachter, University of California, Berkeley, CA, and approved November 16, 2000 (received for review September 8, 2000)

Month of birth influences adult life expectancy at ages 50+. Why? In two countries of the Northern Hemisphere-Austria and Denmark-people born in autumn (October-December) live longer than those born in spring (April-June). Data for Australia show that, in the Southern Hemisphere, the pattern is shifted by half a year. The lifespan pattern of British immigrants to Australia is similar to that of Austrians and Danes and significantly different from that of Australians. These findings are based on population data with more than a million observations and little or no selectivity. The differences in lifespan are independent of the seasonal distribution of deaths and the social differences in the seasonal distribution of births. In the Northern Hemisphere, the excess mortality in the first year of life of infants born in spring does not support the explanation of selective infant survival. Instead, remaining life expectancy at age 50 appears to depend on factors that arise in utero or early in infancy and that increase susceptibility to diseases later in life. This result is consistent with the finding that, at the turn of the last century, infants born in autumn had higher birth weights than those born in other seasons. Furthermore, differences in adult lifespan by month of birth decrease over time and are significantly smaller in more recent cohorts, which benefited from substantial improvements in maternal and infant health.
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The British Journal of Psychiatry 155: 79-85 (1989)
© 1989 The Royal College of Psychiatrists

Mood changes after right-hemisphere lesions
SE Starkstein, RG Robinson, MA Honig, RM Parikh, J Joselyn and TR Price
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Ninety-three patients with acute stroke lesions restricted to the right hemisphere were examined for the presence of mood changes. While 46 patients showed no mood changes, 19 were unduly cheerful, 17 had developed major depression, and 11 had developed minor depression. Although there were no significant between-groups differences in other demographic variables, neurological deficits, activities of daily living, cognitive impairment, or quality of social support, patients with major depression had a significantly higher frequency of familial history of psychiatric disorder and lesions of the parietal cortex than patients with either no mood change or major depression following left- hemisphere lesions. On the other hand, undue cheerfulness was significantly associated with lesions of the right frontal operculum. These findings suggest that major depression following right-hemisphere lesions may have a different aetiology and mechanism than major depression following left frontal or basal ganglia lesions.
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The British Journal of Psychiatry 142: 477-481 (1983)
© 1983 The Royal College of Psychiatrists

Left hemisphere's inability to sustain attention over extended time periods in schizophrenics
S Niwa, K Hiramatsu, T Kameyama, O Saitoh, K Itoh and H Utena

Each hemisphere's ability to sustain attention over extended time periods was investigated in 14 schizophrenics and 17 controls using dichotic detection tasks. Schizophrenics produced significantly higher rates of omission errors, as compared to that of commission errors. The rates of omission errors for schizophrenics fluctuated markedly, while the rates of commission errors remained fairly constant. Primarily due to the fluctuation of omission errors, the detection index decreased progressively when schizophrenics were engaged in right-ear tasks. These results suggest that schizophrenics demonstrate a deficit concerning 'response set', especially in the left hemisphere. It is feasible that there may be a correlation with disturbances in integration mechanisms of both hemispheres in schizophrenics.
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Am J Geriatr Psychiatry 10:36-43, February 2002
© 2002 American Association for Geriatric Psychiatry

Age-Related Decline in Dopamine Transporters
Analysis of Striatal Subregions, Nonlinear Effects, and Hemispheric Asymmetries
Christopher H. van Dyck, M.D., John P. Seibyl, M.D., Robert T. Malison, M.D., Marc Laruelle, M.D., Sami S. Zoghbi, Ph.D., Ronald M. Baldwin, Ph.D. and Robert B. Innis, M.D., Ph.D.
Received June 4, 2001; revised July 24, 2001; accepted July 27, 2001. From the Departments of Psychiatry and Diagnostic Radiology, Yale University School of Medicine, New Haven, CT; and VA Connecticut Healthcare System, West Haven, CT. Address correspondence to Dr. van Dyck, Cognitive Disorders Clinic, Department of Psychiatry, Yale University School of Medicine, One Church Street, Suite 600, New Haven, CT 06510. E-mail: christopher.vandyck@yale.edu

Neuroimaging studies have documented an age-related decline in striatal dopamine transporters (DATs) as a marker of dopaminergic neurodegeneration. The authors further elucidated the effects on this neural system in healthy aging, in contrast to Parkinson disease (PD). The effects of age on striatal DAT availability were examined in a large, healthy subject sample (N=126) with [123I]2ß-carbomethoxy-3ß-(4-iodophenyl)tropane ([123I]ß-CIT) and single photon emission computed tomography (SPECT). Striatal DAT availability (V3'') showed a significant inverse correlation with age, declining in a nearly linear manner by 46% over the age range 18 to 88 years, or 6.6% per decade. Rates of decline were comparable for caudate (48%) and putamen (45%), with only minimal increase in left–right asymmetry with age. Hemispheric asymmetries were unrelated to the handedness of subjects. These results demonstrate that aging is associated with a relatively symmetric loss of DATs in the caudate and putamen in both hemispheres. These findings have implications not only for healthy aging but also for neurodegenerative disorders such as PD.

Key Words: Neuroimaging • Dopamine • Neurophysiology • SPECT
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The British Journal of Psychiatry (2000) 177: 169-173
© 2000 The Royal College of Psychiatrists

Interhemispheric asymmetry of motor cortical excitability in major depression as measured by transcranial magnetic stimulation
FUMIKO MAEDA, MD
Laboratory for Magnetic Brain Stimulation, Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Cambridge, MA and Department of Neuropsychiatry, Keio University School of Medicine, Toyko

JULIAN P. KEENAN, PhD

Laboratory for Magnetic Brain Stimulation, Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Cambridge, MA

ALVARO PASCUAL-LEONE, PhD

Laboratory for Magnetic Brain Stimulation, Behavioral Neurology Unit, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Cambridge, MA and Institute for Bioengineering, Miguel Hernandez Univeristy, Alicante, Spain

Correspondence: Dr A. Pascual-Leone, 330 Brookline Ave. KS452, Boston, MA 02215, USA. Tel: 617-667-0203; Fax: 617-975-5322; e-mail: apleone@caregroup.harvard.edu

Declaration of interest This study was supported in part by the Cellular Science Research Foundation, Yoshida Science Foundation, Stanley Vada Foundation, National Alliance for Research in Schizophrenia and Depression, and the National Institute of Mental Health (ROIMH57980).

Background Neuroimaging studies of major depressive disorder (MDD) indicate interhemispheric differences in prefrontal cortical activity (right greater than left).

Aims To investigate whether there are any interhemispheric differences of motor cortical excitability in MDD.

Method Eight patients with treatment-refractory MDD off medication were assessed for the severity of their depression, and transcranial magnetic stimulation studies (bilateral motor threshold and paired-pulse studies) were conducted. Eight normal controls were also studied.

Results MDD patients showed significant interhemispheric differences in motor threshold and paired-pulse curves, both of which showed lower excitability on the left hemisphere. Such differences were absent in controls.

Conclusions Our findings may aid the further understanding of the neurophysiology underlying MDD.
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The British Journal of Psychiatry (2000) 177: 468
© 2000 The Royal College of Psychiatrists

--------------------------------------------------------------------------------

Correspondence

Transcranial magnetic stimulation: asymmetrical excitability and depression
B. J. Moore
The University Department of Psychiatry, Royal Liverpool University Hospital, Liverpool L69 3GA

EDITED BY MATTHEW HOTOPF

Maeda et al (2000) have succeeded in demonstrating the interhemispheric asymmetry of motor cortical excitability in major depression, using transcranial magnetic stimulation (TMS). This is an important finding that raises questions not only about the pathophysiology of major depression, but also about the state or trait nature of the results.

In discussing possible explanations for this functional asymmetry the authors consider the activity of inhibitory interneurons between cortical output cells, as proposed by Wasserman et al (1996), but it is not clear whether this mechanism is thought to act within the hemisphere being stimulated. The role of transcallosal inhibitory mechanisms has been demonstrated in schizophrenia (Davey et al, 1997; Boroojerdi et al, 1999) and is likely to be relevant to understanding asymmetrical motor thresholds in depression. In support of this view, Menkes et al (1999) hypothesised that depression is associated with decreased left hemisphere excitability with respect to the right hemisphere. They successfully showed that inhibitory low-frequency repetitive TMS applied to the right frontal lobe produced a significant anti-depressant effect, in contrast to exciting the left frontal lobe by means of fast-frequency repetitive TMS, the antidepressant effects of which have been known for some years.

Furthermore, Maeda et al report mean motor thresholds in the depression group of 41.13% for the left hemisphere and 37.63% for the right hemisphere, and in the healthy group of 48.29% for the left hemisphere and 52.7% for the right hemisphere. This gives a mean motor threshold of 39.38% for the depression group and 50.50% for the controls, which suggests important differences in both absolute threshold and laterality between the groups. Any changes to either of these parameters in subjects recovered from depression, and possibly in their first-degree relatives, not only promises new insights into the pathophysiology of depression, but also may provide clues about the most elusive object, a biological marker for depression.

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Brain, Vol 117, Issue 4 729-737, Copyright © 1994 by Oxford University Press

Right hemisphere restitution of language and memory functions in right hemisphere language-dominant patients with left temporal lobe epilepsy
C Helmstaedter, M Kurthen, DB Linke and CE Elger
University Clinic of Epileptology, Bonn, Germany.

Concomitant with the right hemispheric restitution of language functions after early left hemisphere lesions, suppression effects on originally right hemispheric visuospatial/constructional functions have repeatedly been reported. The present study evaluated this issue in 10 right hemisphere language-dominant patients with temporal lobe epilepsy. Left hemisphere language-dominant patients with left (n = 10) or right (n = 10) temporal lobe epilepsy served as controls. The following results were obtained: in all but one of the right dominant patients, left hemisphere lesions, left hemisphere foci and histories of early left brain damage indicated that secondary language transfer rather than a genetically determination is the more likely cause of the right hemisphere dominance. Despite this transfer, the language functions (comprehension, fluency, reasoning) of the right dominant patients remained significantly impaired. Language generally appeared to be better preserved in patients with an onset of epilepsy before the third year of life or a circumscribed left hemisphere lesion. No suppression effects could be detected on the level of complex cortical language and non-language functions. In contrast, on the level of temporo-limbic memory functions, verbal learning and recognition were left largely intact, albeit mostly at the expense of visuo-spatial learning and memory. The findings of the study thus indicate that the cerebral plasticity of the right hemisphere differs according to the extent of the left-hemisphere lesion, the onset of structural/functional damage and the complexity of the functions requiring restitution. Assuming that language and memory represent neocortical and palaeocortical functions, respectively, the restitution process is seemingly governed by their status in a phylogenetically determined hierarchy of functional importance.
==============
Brain, Vol. 123, No. 1, 74-81, January 2000
© 2000 Oxford University Press

Language lateralization in healthy right-handers
S. Knecht, M. Deppe, B. Dräger, L. Bobe, H. Lohmann, E.-B. Ringelstein and H. Henningsen
Department of Neurology, University of Münster, Germany

Correspondence to: Stefan Knecht, MD, Department of Neurology, University of Münster, Albert-Schweitzer-Straße 33, D-48129 Münster, Germany E-mail: knecht@uni-muenster.de

Our knowledge about the variability of cerebral language lateralization is derived from studies of patients with brain lesions and thus possible secondary reorganization of cerebral functions. In healthy right-handed subjects `atypical', i.e. right hemisphere language dominance, has generally been assumed to be exceedingly rare. To test this assumption we measured language lateralization in 188 healthy subjects with moderate and strong right-handedness (59% females) by a new non-invasive, quantitative technique previously validated by direct comparison with the intracarotid amobarbital procedure. During a word generation task the averaged hemispheric perfusion differences within the territories of the middle cerebral arteries were determined. (i) The natural distribution of language lateralization was found to occur along a bimodal continuum. (ii) Lateralization was equivalent in men and women. (iii) Right hemisphere dominance was found in 7.5% of subjects. These findings indicate that atypical language dominance in healthy right-handed subjects of either sex is considerably more common than previously suspected.

Key Words: language lateralization; hemispheric dominance; aphasia; Doppler-ultrasonography

Abbreviations: CBFV = cerebral blood flow velocity; fMRI = functional MRI; fTCD = functional transcranial Doppler-ultrasonography; MCA = middle cerebral arteries
================
Neurology 2001;57:1018-1024
© 2001 American Academy of Neurology

Language and spatial attention can lateralize to the same hemisphere in healthy humans
A. Flöel, MD, S. Knecht, MD, H. Lohmann, MA, M. Deppe, PhD, J. Sommer, MA, B. Dräger, MD, E.-B. Ringelstein, MD and H. Henningsen, MD
From the Department of Neurology, University of Münster, Germany.

Address correspondence and reprint requests to Dr. Agnes Flöel, Department of Neurology, University of Münster, Albert-Schweitzer-Straße 33, D-48129 Münster, Germany; e-mail: floeel@uni-muenster.de

Background:— Disorders of language classically occur after left brain lesions, and disorders of spatial attention after right brain lesions. It is unclear whether the hemispheric dissociation of functions is a fixed pattern of brain organization.

Objective:— The authors determined whether lateralization of language and lateralization of spatial attention also dissociate in people with atypical (i.e., right hemispheric) language dominance.

Methods:— The authors selected 10 subjects with typical, i.e., left hemispheric, and 10 with atypical, i.e., right hemispheric, language representation on a random basis from a sample of 326 healthy volunteers examined with functional transcranial Doppler sonography (fTCD) for language dominance. In these subjects, hemispheric lateralization of cerebral perfusion during a line bisection task was determined with fTCD.

Results:— The authors found a dissociation between dominance for language and spatial attention in all but four subjects. In the latter subjects, there was a significant lateralization to the right hemisphere for both tasks. The four subjects showed normal intellectual, linguistic, and spatial performance, with normal EEG and MRI scans of the brain.

Conclusion:— Even in the absence of brain pathology, the same hemisphere can be dominant in control of both language and spatial attention.
========================
Brain, Vol 119, Issue 4 1255-1262, Copyright © 1996 by Oxford University Press

Collaboration between the hemispheres of a callosotomy patient. Emerging right hemisphere speech and the left hemisphere interpreter
MS Gazzaniga, JC Eliassen, L Nisenson, CM Wessinger, R Fendrich and K Baynes
Center for Neuroscience, University of California Davis, USA.

Split brain patients who are initially unable to produce speech in their right hemispheres sometimes develop the ability to do so. Patient J.W., the subject of this report, is such a patient. At the time of his callosotomy, J.W. had a language dominant left hemisphere; his right hemisphere could understand both spoken and written language, but he was unable to speak. Fourteen years after his surgery, we found that J.W. was capable of naming approximately 25% of the stimuli presented to his left visual field (LVF). Now, 1 year later, we find that he can name about 60% of such stimuli. This late-developing speech ability appears to be consequence of long-term neural plasticity. However, the subject's extended verbal responses to LVF stimuli seem to result from a collaboration between the hemispheres and to involve the left hemisphere interpreter.
================
Brain, Vol. 122, No. 7, 1317-1325, July 1999
© 1999 Oxford University Press

Semantic integration in reading: engagement of the right hemisphere during discourse processing
M. St George, M. Kutas, A. Martinez and M. I. Sereno
University of California, San Diego, USA

Correspondence to: Marie St George, Center for Research in Language, 0526, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0526, USA E-mail: stgeorge@crl.ucsd.edu

We examined the brain areas involved in discourse processing by using functional MRI in 10 individuals as they read paragraphs, with or without a title, word by word for comprehension. Functional data were collected from 20 adjacent 5 mm axial slices. Discourse processing was associated with activation in inferior frontal and temporal regions of both cerebral hemispheres in the titled and untitled conditions. Moreover, there was substantially more right hemisphere activation for untitled than for the titled paragraphs. More specifically we found: (i) greater activation in the inferior temporal sulcus of both hemispheres for untitled than titled paragraphs; (ii) greater average volume of activation in response to untitled than titled paragraphs in the middle temporal sulcus of the right hemisphere and the reverse pattern in the left middle temporal sulcus. Consistent with previous studies of individuals with right hemisphere damage, we suggest that the right middle temporal regions may be especially important for integrative processes needed to achieve global coherence during discourse processing.

Key Words: functional MRI; language; semantic integration; right hemisphere

Abbreviations: BA = Brodmann area; ERP = event-related brain potential; fMRI = functional MRI

=============
(Journal of Cognitive Neuroscience. 2002;14:550-560.)
© 2002 The MIT Press

The Response of Left Temporal Cortex to Sentences
R. Vandenberghe
University Hospital Gasthuisberg, Leuven

A.C. Nobre

Oxford University

C.J. Price

University College London

The meaning of a sentence differs from the sum of the meanings of its constituents. Left anterior temporal cortex responds to sentences more strongly than to unconnected words. We hypothesized that the anterior temporal response to sentences is due to this difference in meaning (compositional semantics). Using positron emission tomography (PET), we studied four experimental conditions (2 x 2 factorial design): In one condition, subjects read normal sentences. In a second condition, they read grammatically correct sentences containing numerous semantic violations (semantically random sentences). In a third condition, we scrambled the word order within the normal sentences, and, in a fourth condition, the word order was scrambled within the semantically random sentences. The left anterior temporal pole responded strongly to sentences compared to scrambled versions of sentences. A similar although weaker response occurred in the left anterior superior temporal sulcus and the left posterior middle temporal gyrus. A subset of voxels within the left anterior temporal pole responded more to semantically random sentences and their scrambled versions than to normal sentences and the corresponding scrambled versions (main effect of semantic randomness). Finally, the grammatical and the semantic factor interacted in a subset of voxels within the anterior temporal pole: Activity was higher when subjects read normal sentences compared to their scrambled versions but not for semantically random sentences compared to their corresponding scrambled versions. The effects of grammar and meaning and, most importantly, the interaction between grammatical and semantic factors are compatible with the hypothesis that the left anterior temporal pole contributes to the composition of sentence meaning.
==================
Brain, Vol. 124, No. 10, 2028-2044, October 2001
© 2001 Oxford University Press

The neural organization of discourse
An H215O-PET study of narrative production in English and American sign language
A. R. Braun, A. Guillemin, L. Hosey and M. Varga
Language Section, Voice Speech and Language Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, USA

Correspondence to: A. R. Braun, MD, Language Section, Voice Speech and Language Branch, National Institute on Deafness and Other Communication Disorders, Building 10, Room 5N118A, 10 Center Drive MSC 1407, National Institutes of Health, Bethesda, MD 20892, USA E-mail: brauna@nidcd.nih.gov

In order to identify brain regions that play an essential role in the production of discourse, H215O-PET scans were acquired during spontaneous generation of autobiographical narratives in English and in American Sign Language in hearing subjects who were native users of both. We compared languages that differ maximally in their mode of expression yet share the same core linguistic properties in order to differentiate the stages of discourse production: differences between the languages should reflect later, modality-dependent stages of phonological encoding and articulation; congruencies are more likely to reveal the anatomy of earlier modality-independent stages of conceptualization and lexical access. Common activations were detected in a widespread array of regions; left hemisphere language areas classically related to speech were also robustly activated during sign production, but the common neural architecture extended beyond the classical language areas and included extrasylvian regions in both right and left hemispheres. Furthermore, posterior perisylvian and basal temporal regions appear to play an integral role in spontaneous self-generated formulation and production of language, even in the absence of exteroceptive stimuli. Results additionally indicate that anterior and posterior areas may play distinct roles in early and late stages of language production, and suggest a novel model for lateralization of cerebral activity during the generation of discourse: progression from the early stages of lexical access to later stages of articulatory–motor encoding may constitute a progression from bilateral to left-lateralized activation. This pattern is not predicted by the standard Wernicke–Geschwind model, and may become apparent when language is produced in an ecologically valid context.
=============
Brain, Vol. 125, No. 8, 1829-1838, August 2002
© 2002 Guarantors of Brain

Speech production: Wernicke, Broca and beyond
S. Catrin Blank1, Sophie K. Scott2, Kevin Murphy3, Elizabeth Warburton4 and Richard J. S. Wise1
1 MRC Clinical Sciences Centre, Cyclotron Unit, Hammersmith Hospital, 2 Department of Psychology, University College London, 3 Department of Respiratory Medicine, Imperial College School of Medicine, Charing Cross Hospital, London and 4 Department of Neuroscience, Addenbrooke’s Hospital, Cambridge, UK

Correspondence to: Dr Catrin Blank, MRC Clinical Sciences Centre, Cyclotron Unit, Hammersmith Hospital, Du Cane Road, London W12 0NN, UKE-mail: katrin.blank@ic.ac.uk

We investigated the brain systems engaged during propositional speech (PrSp) and two forms of non- propositional speech (NPrSp): counting and reciting overlearned nursery rhymes. Bilateral cerebral and cerebellar regions were involved in the motor act of articulation, irrespective of the type of speech. Three additional, left-lateralized regions, adjacent to the Sylvian sulcus, were activated in common: the most posterior part of the supratemporal plane, the lateral part of the pars opercularis in the posterior inferior frontal gyrus and the anterior insula. Therefore, both NPrSp and PrSp were dependent on the same discrete subregions of the anatomically ill-defined areas of Wernicke and Broca. PrSp was also dependent on a predominantly left-lateralized neural system distributed between multi-modal and amodal regions in posterior inferior parietal, anterolateral and medial temporal and medial prefrontal cortex. The lateral prefrontal and paracingulate cortical activity observed in previous studies of cued word retrieval was not seen with either NPrSp or PrSp, demonstrating that normal brain- language representations cannot be inferred from explicit metalinguistic tasks. The evidence from this study indicates that normal communicative speech is dependent on a number of left hemisphere regions remote from the classic language areas of Wernicke and Broca. Destruction or disconnection of discrete left extrasylvian and perisylvian cortical regions, rather than the total extent of damage to perisylvian cortex, will account for the qualitative and quantitative differences in the impaired speech production observed in aphasic stroke patients.
===============
Brain, Vol 121, Issue 12 2369-2379, Copyright © 1998 by Oxford University Press

Morphology of the planum temporale and corpus callosum in left handers with evidence of left and right hemisphere speech representation
SD Moffat, E Hampson and DH Lee
Department of Psychology, University of Western Ontario, London, Canada.

In the present study we investigated planum temporale asymmetry and corpus callosum morphology in a sample of young adult left-handed males, using MRI. Two subgroups of left-handed males were identified on the basis of their differing speech lateralization patterns, which were inferred from results of the Fused Dichotic Words Test. These individuals then underwent MRI in order to obtain area measurements of the left and right planum temporale and the midsagittal corpus callosum. Comparisons between these left-handed males and an archival sample of age-matched right-handed males were also performed. Results demonstrated a strong leftward asymmetry in the planum temporale among subjects with left-hemisphere speech representation, regardless of handedness, but no consistent planum temporale asymmetry among subjects with right hemisphere speech representation. The results suggest that reversed speech lateralization is not necessarily accompanied by a concomitant reversal of planum temporale asymmetry. Examination of callosal areas revealed that left-handed subjects with left hemisphere speech functions had a larger corpus callosum than either left-handed subjects with right hemisphere speech functions or right-handed subjects. Increased interhemispheric communication may be required when the neural systems underlying speech and handedness are represented in opposite hemispheres.
===================
Brain, Vol 117, Issue 6 1241-1253, Copyright © 1994 by Oxford University Press

The role of the right hemisphere in the interpretation of figurative aspects of language. A positron emission tomography activation study
G Bottini, R Corcoran, R Sterzi, E Paulesu, P Schenone, P Scarpa, RS Frackowiak and CD Frith
MRC Clinical Sciences Centre, Hammersmith Hospital, London, UK.

We investigated cerebral activity in six normal volunteers using PET to explore the hypothesis that the right hemisphere has a specific role in the interpretation of figurative aspects of language such as metaphors. We also mapped the anatomical structures involved in sentence comprehension. During regional cerebral blood flow measurement subjects were asked to perform three different linguistic tasks: (i) metaphorical comprehension; (ii) literal comprehension of sentences; and (iii) a lexical-decision task. We found that comprehension of sentences compared with the lexical-decision task, induced extensive activation in several regions of the left hemisphere, including the prefrontal and basal frontal cortex, the middle and inferior temporal gyri and temporal pole, the parietal cortex and the precuneus. Comprehension of metaphors was associated with similar activations in the left hemisphere, but in addition, a number of sites were activated in the right hemisphere: the prefrontal cortex, the middle temporal gyrus, the precuneus and the posterior cingulate. We conclude that the interpretation of language involves widespread distributed systems bilaterally with the right hemisphere having a special role in the appreciation of metaphors.
===================
Brain, Vol. 125, No. 9, 2067-2080, September 2002
© 2002 Guarantors of Brain

Can segregation within the semantic system account for category-specific deficits?
Jacqueline A. Phillips1, Uta Noppeney1, Glyn W. Humphreys2 and Cathy J. Price1
1 The Wellcome Department of Cognitive Neurology, Institute of Neurology, London and 2 Behavioural Brain Sciences, School of Psychology, University of Birmingham, Birmingham, UK

Correspondence to: Dr Cathy Price, Wellcome Department of Cognitive Neurology, 12 Queen Square, London WC1N 3BG, UK E-mail: c.price@fil.ion.ucl.ac.uk

Functional neuroimaging was used to investigate the extent to which category-specific semantic deficits in patients can be accounted for in terms of the demands placed on neural systems underlying different types of semantic knowledge. Unlike previous functional imaging studies of category specificity, we used a factorial design that crossed category (tools and fruits) with tasks requiring retrieval of either action or perceptual (real life size) knowledge. The presentation of tools relative to fruit increased activation in the same left posterior middle temporal area that was linked to the retrieval of action knowledge in general (for fruit as well as tools). However, we found no correlation between activation evoked by fruit and the size retrieval task. The left medial anterior temporal cortex was the only region to be activated for fruit relative to tools. We argue that the sensory–functional theory of category-specific effects is insufficient to account for the current neuroimaging literature. However, the data do support a more refined version of the theory: tools, relative to fruit, are more strongly linked to manipulative/motor knowledge and, for some tasks, fruit may be more reliant on integrating multiple semantic features.
===============
Brain, Vol. 122, No. 7, 1317-1325, July 1999
© 1999 Oxford University Press

Semantic integration in reading: engagement of the right hemisphere during discourse processing
M. St George, M. Kutas, A. Martinez and M. I. Sereno
University of California, San Diego, USA

Correspondence to: Marie St George, Center for Research in Language, 0526, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0526, USA E-mail: stgeorge@crl.ucsd.edu

We examined the brain areas involved in discourse processing by using functional MRI in 10 individuals as they read paragraphs, with or without a title, word by word for comprehension. Functional data were collected from 20 adjacent 5 mm axial slices. Discourse processing was associated with activation in inferior frontal and temporal regions of both cerebral hemispheres in the titled and untitled conditions. Moreover, there was substantially more right hemisphere activation for untitled than for the titled paragraphs. More specifically we found: (i) greater activation in the inferior temporal sulcus of both hemispheres for untitled than titled paragraphs; (ii) greater average volume of activation in response to untitled than titled paragraphs in the middle temporal sulcus of the right hemisphere and the reverse pattern in the left middle temporal sulcus. Consistent with previous studies of individuals with right hemisphere damage, we suggest that the right middle temporal regions may be especially important for integrative processes needed to achieve global coherence during discourse processing.

Key Words: functional MRI; language; semantic integration; right hemisphere

Abbreviations: BA = Brodmann area; ERP = event-related brain potential; fMRI = functional MRI
================
PNAS Vol. 95, Issue 5, 2703-2708, March 3, 1998

Psychology-BS
Neural correlates of the episodic encoding of pictures and words
Cheryl L. Grady*, Anthony R. McIntosh, M. Natasha Rajah, and Fergus I. M. Craik
Rotman Research Institute of Baycrest Centre and Department of Psychology, University of Toronto, 3560 Bathurst Street, Toronto, Ontario, Canada, M6A 2E1

Communicated by Endel Tulving, Rotman Research Institute of Baycrest Centre, Toronto, Canada, December 8, 1997 (received for review August 15, 1997)

A striking characteristic of human memory is that pictures are remembered better than words. We examined the neural correlates of memory for pictures and words in the context of episodic memory encoding to determine material-specific differences in brain activity patterns. To do this, we used positron emission tomography to map the brain regions active during encoding of words and pictures of objects. Encoding was carried out by using three different strategies to explore possible interactions between material specificity and types of processing. Encoding of pictures resulted in greater activity of bilateral visual and medial temporal cortices, compared with encoding words, whereas encoding of words was associated with increased activity in prefrontal and temporoparietal regions related to language function. Each encoding strategy was characterized by a distinctive activity pattern, but these patterns were largely the same for pictures and words. Thus, superior overall memory for pictures may be mediated by more effective and automatic engagement of areas important for visual memory, including medial temporal cortex, whereas the mechanisms underlying specific encoding strategies appear to operate similarly on pictures and words.
================
Brain, Vol 112, Issue 1 39-63, Copyright © 1989 by Oxford University Press

Reading with one hemisphere
K Patterson, F Vargha-Khadem and CE Polkey
MRC Applied Psychology Unit, Cambridge, UK.

The subjects of this study were 2 originally right-handed teen-aged girls who had undergone complete hemispherectomy (1 left, 1 right) for intractable epilepsy. Both subjects had developed normal language and reading capacities before the onset of their illness. The reading performance of H.P. (whose right hemisphere had been removed), while not as advanced in level as that of a normal 17-yr-old, showed no abnormality in any subcomponent of reading skill. The reading performance of N.I. (whose left hemisphere had been removed) was poor, but with a pattern of retained and impaired subskills strikingly similar to adult deep dyslexic patients and to split-brain patients given reading tasks lateralized to the left visual field (right hemisphere). The results are discussed with regard to implications for the reading capacity of the nondominant right hemisphere and also its putative contribution to normal reading.
================
(Journal of Cognitive Neuroscience. 2001;13:341-356.)
© 2001 The MIT Press

No Right to Speak? The Relationship Between Object Naming and Semantic Impairment: Neuropsychological Evidence and a Computational Model
M.A. Lambon Ralph
University of Bristol, Bristol, UK

J.L. McClelland

Center for the Neural Basis of Cognition, Pittsburgh

K. Patterson

MRC Cognition and Brain Sciences Unit, Cambridge, UK

C.J. Galton

Addenbrooke's Hospital, Cambridge, UK

J.R. Hodges

MRC Cognition and Brain Sciences Unit, Cambridge, UK
Addenbrooke's Hospital, Cambridge, UK

The processes required for object naming were addressed in a study of patients with semantic dementia (a selective decline of semantic memory resulting from progressive temporal lobe atrophy) and in a computational model of single-word production. Although all patients with semantic dementia are impaired in both single-word production and comprehension, previous reports had indicated two different patterns: (a) a parallel decline in accuracy of naming and comprehension, with frequent semantic naming errors, suggesting a purely semantic basis for the anomia and (b) a dramatic progressive anomia without commensurate decline in comprehension, which might suggest a mainly postsemantic source of the anomia. Longitudinal data for 16 patients with semantic dementia reflected these two profiles, but with the following additional important specifications: (1) despite a few relatively extreme versions of one or other profile, the full set of cases formed a continuum in the extent of anomia for a given degree of degraded comprehension; (2) the degree of disparity between these two abilities was associated with relative asymmetry in laterality of atrophy: a parallel decline in the two measures characterized patients with greater right- than left-temporal atrophy, while disproportionate anomia occurred with a predominance of atrophy in the left-temporal lobe. In an implemented computational model of naming, semantic representations were distributed across simulated left- and right-temporal regions, but the semantic units on the left were more strongly connected to left-lateralized phonological representations. Asymmetric damage to semantic units reproduced the longitudinal patient profiles of naming relative to comprehension, plus additional characteristics of the patients' naming performance. On the basis of both the neuropsychological and computational evidence, we propose that semantic impairment alone can account for the full range of word production deficits described here.
===============
Brain, Vol 107, Issue 1 145-153, Copyright © 1984 by Oxford University Press

Dissociation of language and cognition. A psychological profile of two disconnected right hemispheres
MS Gazzaniga and CS Smylie

Two split-brain patients who differ in their right hemisphere language capacity were tested on a variety of simple cognitive tasks. Both isolated right hemispheres performed poorly on most tests. The results suggest that the presence of language in the right hemisphere, a brain system that ordinarily does not possess such competence, need not necessarily confer the full complement of cognitive skills associated with the language processing skills of the left hemisphere.
================
American Journal of Neuroradiology 21:1048-1054 (6 2000)
© 2000 American Society of Neuroradiology

Cerebral Activation during Multiplication: A Functional MR Imaging Study of Number Processing
Robert K. Fulbright,a, David L. Molfesea, Alexander A. Stevensa, Pawel Skudlarskia, Cheryl M. Lacadiea and John C. Gorea
a From the Departments of Diagnostic Radiology (R.K.F., P.S., C.M.L., J.C.G.) and Applied Physics (J.C.G.), Yale University, 333 Cedar Street, New Haven, CT; the Department of Cognitive Science (D.L.M.), University of California at San Diego, La Jolla, CA; and the Department of Psychiatry (A.A.S.), Oregon Health Sciences University, Portland, OR.

BACKGROUND AND PURPOSE: Current models of brain function propose that number processing involves the interaction of different neuronal networks. Our purpose was to use functional MR (fMR) imaging to elucidate the brain regions engaged by multiplication.

METHODS: Eighteen adults underwent fMR imaging while performing matching, multiplication, and control tasks. For each task, three or four single-digit or low-value double-digit numbers were presented serially followed by a 12-second delay. A target stimulus then appeared and subjects made a judgement by pressing a button box that recorded responses. During the matching task, subjects judged whether the target stimulus matched one of the previous numbers. During the multiplication task, subjects judged whether the target stimulus was the product of the previous numbers. For the control task, the numbers were always zeros, and the subjects responded to a target stimulus that was always four zeros. Composite statistical parametric maps of the time course of activation comparing the control task with the matching and multiplication tasks, respectively, were generated and the significance of signal changes was estimated by randomization of statistical parametric maps.

RESULTS: The matching and multiplication tasks resulted in activation (P < .005) in the medial superior frontal gyrus; the anterior cingulate gyrus; the intraparietal sulci, bilaterally; the right superior frontal sulcus bilaterally; the middle, inferior and precentral frontal gyri (left greater than right); the left basal ganglia; and the right lateral and inferior occipital gyri. There was a larger area of early activation in the right middle frontal gyrus during the matching task compared with the multiplication task, and there was a longer interval of activation in the left middle frontal gyrus during the multiplication task (10 seconds) than in the matching task (6 seconds).

CONCLUSION: Multiplication and memory of numbers share an integrated network of brain regions. The left frontal lobe, an area also involved in memory and language processes, appears to play an important role in multiplication.

**********SELF-REFERENCING***********
====================================
(Journal of Cognitive Neuroscience. 1999;11:617-630.)
© 1999 The MIT Press

Differential Contributions of the Left and Right Inferior Parietal Lobules to Number Processing
F. Chochna, L. Cohenb, P. F. van de Moortelec and S. Dehaenec
a INSERM U334, Orsay, France
b INSERM U334, Orsay and Hôpital de la Salpêtrière, Paris, France
c INSERM U334, Orsay, France

We measured cerebral activation with functional magnetic resonance imaging at 3 Tesla while eight healthy volunteers performed various number processing tasks known to be dissociable in brain-lesioned patients: naming, comparing, multiplying, or subtracting single digits. The results revealed the activation of a circuit comprising bilateral intraparietal, prefrontal, and anterior cingulate components. The extension and lateralization of this circuit was modulated by task demands. The intraparietal and prefrontal activation was more important in the right hemisphere during the comparison task and in the left hemisphere during the multiplication task and was intensely bilateral during the subtraction task. Thus, partially distinct cerebral circuits with the dorsal parietal pathway underlie distinct arithmetic operations
===================
Cerebral Cortex, Vol. 11, No. 4, 350-359, April 2001
© 2001 Oxford University Press

Dissociating Neural Correlates of Cognitive Components in Mental Calculation
O. Gruber1,2, P. Indefrey3, H. Steinmetz4 and A. Kleinschmidt4
1 Max-Planck-Institute of Cognitive Neuroscience, Leipzig, Germany,
2 Institute of Medicine, Research Center Jülich, Jülich, Germany,
3 Max-Planck-Institute for Psycholinguistics, Nijmegen, The Netherlands and
4 Department of Neurology, University of Frankfurt, Frankfurt, Germany

Mental calculation is a complex cognitive operation that is composed of a set of distinct functional processes. Using functional magnetic resonance imaging (fMRI), we mapped brain activity in healthy subjects performing arithmetical tasks and control tasks evoking a comparable load on visuo-constructive, linguistic, attentional and mnemonic functions. During calculation, as well as non-mathematical tasks, similar cortical networks consisting of bilateral prefrontal, premotor and parietal regions were activated, suggesting that most of these cortical areas do not exclusively represent modules for calculation but support more general cognitive operations that are instrumental but not specific to mental arithmetic. Significant differences between calculation and the non-mathematical tasks were found in parietal sub-regions, where non-arithmetic number or letter substitution tasks preferentially activated the superior parietal lobules whereas calculation predominantly elicited activation of the left dorsal angular gyrus and the medial parietal cortices. We interpret the latter activations to reflect sub-processes of mental calculation that are related to the processing of numerical representations during exact calculation and to arithmetical fact retrieval. Finally, we found that more complex calculation tasks involving the application of calculation rules increased activity in left inferior frontal areas that are known to subserve linguistic and working memory functions. Taken together, these findings help to embed the specific cognitive operation of calculation into a neural framework that provides the required set of instrumental components. This result may further inform the cognitive modeling of calculation and adds to the understanding of neuropsychological deficit patterns in patients.
=============
Brain, Vol 119, Issue 6 1983-1990, Copyright © 1996 by Oxford University Press

Age and hemisphere effects on dendritic structure
B Anderson and V Rutledge
Department of Neurology, University of Alabama at Birmingham 35294- 0007, USA.

The dendritic structures of 187 small supragranular pyramidal neurons of the posterior superior temporal gyrus were studied with rapid Golgi impregnations in postmortem samples from 10 men aged 21-71 years. The number of primary basilar dendritic branches, the total number of basilar dendritic endings, the total basilar dendritic length, the total number of visible basilar dendritic spines and the cell soma sizes were all positively inter-correlated and all features were correlated to age (r = -0.77, -0.88, -0.82, -0.72, -0.86, respectively; all P < 0.05). These neuronal measures all correlated with brain weight (r = 0.79*, 0.65*, 0.51, 0.45, 0.55, respectively; *denotes P < 0.05). A first principle component derived from the inter-correlations of the neuronal features plus brain weight correlated almost perfectly with age (r = -0.93). The neuronal features differed between the right and left hemispheres (Wilks' Lambda = 0.91, P < 0.01). Post hoc tests showed that the dendritic trees of the right hemisphere were longer (P = 0.002), more branched (P = 0.008) and possessed more dendritic spines (P = 0.0009; Sheffe's tests). In conclusion, there are hemispheric differences in the dendritic structure of the small pyramidal neurons of presumptive human speech cortex and its right hemisphere analogue. Generalized neuronal atrophy is highly correlated with both brain weight and age, and is a candidate process to explain the decline in cognition with age.
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Brain, Vol 114, Issue 3 1441-1456, Copyright © 1991 by Oxford University Press

Hemisphere asymmetry in decision making abilities. An experimental study in unilateral brain damage
A Tartaglione, ML Inglese, F Bandini, L Spadavecchia, K Hamsher and E Favale
Clinica Neurologica dell'Universita di Genova, Italy.

Thirty control subjects and 60 unilateral brain-damaged patients, 30 with left hemisphere (LH) damage and 30 with right hemisphere (RH) disease, underwent a disjunctive 4-choice reaction time study. Speed of reaction (as defined by the reciprocal of reaction time (RT), movement time (MT) and total response time (TRT] and accuracy of response (as represented by the sum of errors in selecting the correct response key) were investigated comparatively as a function of side of lesion and of performance on Raven's Coloured Progressive Matrices (PM47). In contrast to movement speed (1/MT), reaction speed (1/RT) as well as total response speed (1/TRT) showed a lesion effect independent of side of damage. Conversely, accuracy was differentially impaired, LH damage being associated with a significantly higher number of errors. Speed and accuracy had different relationships with the performance on the PM47 in the two hemisphere groups. Speed was affected in parallel with changes in PM47 performance both in the LH and in RH groups, whereas accuracy was altered only in LH patients. It was concluded that speed of motor reaction is affected by unilateral brain lesions irrespective of their side, whereas decision making processes, as expressed by accuracy of response, seem to be specifically impaired by LH damage.
================
Brain, Vol 109, Issue 3 547-560, Copyright © 1986 by Oxford University Press

Memory for scenes in stroke patients. Hemisphere processing of semantic organization in pictures
DW Zaidel

Twenty-one patients with cerebrovascular lesions in posterior regions of the left or right cerebral hemispheres and nonfluent aphasics with damage in anterior regions of the left hemisphere were administered a specially designed multiple-object pictorial test which measured long- term memory for scenes depicting real world schemata versus jumbled unorganized scenes. The units in the pictures were familiar figures. Memory was tested separately for single details and for whole scenes. The results showed that within the left posterior group there was significantly poorer memory for unorganized relative to organized stimuli, especially for whole scenes. There was also a selective dissociation between the left and right posterior patients on the detail versus whole scene probes in the unorganized stimuli. At the same time, organized scenes depicting real world schemata were not selectively impaired in any of the patient groups. Further, the overall memory scores on the Memory for Pictorial Scenes Test obtained by the aphasic patients were not significantly lower than those obtained by the control subjects, while scores of both posterior groups were lower than the control group. Taken together, the data suggest the following. Pictorial semantics, like linguistic semantics, are functions processed by the left posterior cortex. While the posterior region in the left hemisphere plays a special role in remembering visual situational schemata that are newly encountered, familiar visual situational schemata may be bilaterally represented.
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: Behav Brain Res 2001 Jul;122(1):57-65

Role of right hemifield in visual control of approach to target in zebrafish.

Miklosi A, Andrew RJ, Gasparini S.

Department of Ethology, Eotvos University, God, S.u. 14, H-2131, Javorka, Hungary.

When a zebrafish has to choose between two identical stimuli (e.g. a conditioned stimulus, CS, for food reward), it tends to respond to the one on its right. Errors are more numerous when reinforced for taking the one on the left rather than the one on the right. When trained to a single medial stimulus, and presented in non-reinforced probe trials with a pair of identical stimuli, the one on the right is chosen. Use by zebrafish of right eye (RE), viewing to control a planned motor response, extends from objects that are to be bitten to a choice of one of two routes. When the CS is visible behind a barrier of vertical bars, so that it can be approached around either end, it is the right end that is chosen. Standing motor bias independent of the nature of the task can be excluded. Other vertebrates show RE control of response. Toads are more likely to take food seen with the RE. The domestic chick uses the RE in visual control of approach to an object that has to be manipulated with the bill. RE control of use of the mouth in a fish shows that that this is an earlier condition than lateralised control of bilateral effectors like hands.

Behav Brain Res 1999 Nov 15;105(2):199-205

Right eye use associated with decision to bite in zebrafish.

Miklosi A, Andrew RJ.

Centre for Neuroscience, School of Biology, University of Sussex, Brighton, UK.

Cerebral lateralisation is revealed in the zebrafish by preferential eye use, which differs according to the visual stimulus that is being fixated. Past findings [Bisazza A, Pignatti R, Vallortigara G. Behav. Brain Res. 1997b;89:237-242; Miklosi A, Andrew RJ, Savage, H. Physiol. Behav. 1998;63:127 135] suggest that the right eye is used when the stimulus (or scene) is such as to require a careful period of examination in order to decide on a response. The left eye is used when the fish has to check whether an identical stimulus has been seen before. We here show that the same association of right eye use with decision to respond holds for biting at small targets (coloured or black and white beads). Biting and right eye use were both high at the first presentation of both types of bead, and fell together over two further trials with the same type of bead. At the fourth trial the appearance of the bead was changed. A change in colour caused both right eye use and biting to return, whereas a change in orientation of the black stripe on the black and white bead had no effect on either (and seemed to be largely ignored). In the case of the coloured beads, habituation of biting was accompanied by continued interest, shown by increased binocular fixation. The reduction in reliance on right eye viewing thus represents a change in the strategy of analysis rather than coming to ignore the stimulus. It would allow a greater involvement of the left eye system.

(IDM*** if the brain crossover is valid then right eye = left, and left eye = right. Note how the right eye reflects detail and the left reflects pattern matching.)

Am J Med Genet 2000 Winter;97(4):271-9

Left-right asymmetry and cardiac looping: implications for cardiac development and congenital heart disease.

Kathiriya IS, Srivastava D.

Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, 75390-9148, USA.

Proper morphogenesis and positioning of internal organs requires delivery and interpretation of precise signals along the anterior-posterior, dorsal-ventral, and left-right axes. An elegant signaling cascade determines left- versus right-sided identity in visceral organs in a concordant fashion, resulting in a predictable left-right (LR) organ asymmetry in all vertebrates. The complex morphogenesis of the heart and its connections to the vasculature are particularly dependent upon coordinated LR signaling pathways. Disorganization of LR signals can result in myriad congenital heart defects that are a consequence of abnormal looping and remodeling of the primitive heart tube into a multi-chambered organ. A framework for understanding how LR asymmetric signals contribute to normal organogenesis has emerged and begins to explain the basis of many human diseases of LR asymmetry. Here we review the impact of LR signaling pathways on cardiac development and congenital heart disease.

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Brain, Vol. 125, No. 2, 373-383, February 1, 2002
© 2002 Oxford University Press

Power and coherence of sleep spindle frequency activity following hemispheric stroke
J. M. Gottselig1, C. L. Bassetti2 and P. Achermann1
1 Institute of Pharmacology and Toxicology, Section of Psychopharmacology and Sleep Research, University of Zürich and 2 Department of Neurology, University Hospital-Inselspital, Bern, Switzerland

Correspondence to: Dr Peter Achermann, Institute of Pharmacology and Toxicology, Section of Psychopharmacology and Sleep Research, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland E-mail: acherman@pharma.unizh.ch

Brainstem and thalamic structures are known to play a critical role in modulating sleep–wake cycles, but the extent to which the cerebral hemispheres are involved remains unclear. To study the role of the cerebral hemispheres in generating sleep EEG patterns, all-night polysomnographic recordings were collected in subjects with brain damage (n = 30) caused by hemispheric stroke and in hospitalized controls (n = 12). Recordings were made in the acute (10 days post-stroke), subchronic (11–35 days post-stroke) and chronic (>60 days post-stroke) phases of stroke. Bipolar and referential EEG derivations were recorded. Standard sleep stage scoring was conducted using the referential derivation placed opposite the lesion. Sleep stage 2 power and coherence spectra were calculated based on recordings from bipolar derivations. In the mean spectra, the highest spindle frequency peak was identified and its size was calculated relative to the background spectrum. Analysis of visually scored EEG data indicated that, compared with controls, acute phase brain-damaged subjects had lower sleep efficiency and increased waking after sleep onset. The durations of rapid eye movement and non-rapid eye movement sleep stages did not differ significantly between brain-damaged subjects and hospitalized controls. Spectral analyses revealed that, compared with hospitalized controls, brain-damaged subjects had significantly reduced spindle peak sizes in the power and coherence spectra from derivations ipsilateral to the lesion. Within-subject comparisons across time demonstrated that the power and coherence of sleep spindle frequency activity increased significantly from the acute to the chronic phases of stroke, suggesting that plastic mechanisms allowed the possibility of recovery. Our findings provide novel evidence that the cerebral hemispheres are important in generating coherent sleep spindles in humans, and they are consonant with prior empirical and theoretical evidence that corticothalamic projections modulate the generation of synchronous spindle oscillations. Because spindle oscillations are thought to be involved in blocking sensory input to the cortex during sleep, the decrease in synchronous spindle frequency activity following hemispheric stroke may contribute to the observed reduction in sleep continuity.
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Brain, Vol. 123, No. 12, 2512-2518, December 2000
© 2000 Oxford University Press

Handedness and hemispheric language dominance in healthy humans
S. Knecht, B. Dräger, M. Deppe, L. Bobe, H. Lohmann, A. Flöel, E.-B. Ringelstein and H. Henningsen
Department of Neurology, University of Münster, Germany

Correspondence to: Stefan Knecht, MD, Department of Neurology, University of Münster, Albert-Schweitzer-Strasse 33, D-48129 Münster, Germany E-mail: knecht@uni-muenster.de

In most people the left hemisphere of the brain is dominant for language. Because of the increased incidence of atypical right-hemispheric language in left-handed neurological patients, a systematic association between handedness and dominance has long been suspected. To clarify the relationship between handedness and language dominance in healthy subjects, we measured lateralization directly by functional transcranial Doppler sonography in 326 healthy individuals using a word-generation task. The incidence of right-hemisphere language dominance was found to increase linearly with the degree of left-handedness, from 4% in strong right-handers (handedness = 100) to 15% in ambidextrous individuals and 27% in strong left-handers (handedness = –100). The relationship could be approximated by the formula: . These results clearly demonstrate that the relationship between handedness and language dominance is not an artefact of cerebral pathology but a natural phenomenon.
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Neurology 2002;59:238-244
© 2002 American Academy of Neurology

Language lateralization in left-handed and ambidextrous people
fMRI data
J. P. Szaflarski, MD PhD, J. R. Binder, MD, E. T. Possing, MS, K. A. McKiernan, PhD, B. D. Ward, MS and T. A. Hammeke, PhD
From the Department of Neurology (Dr. Szaflarski), University of Cincinnati Medical Center, OH; and Department of Neurology (Drs. Binder, McKiernan, and Hammeke, and E. Possing), and Biophysics Research Institute (B. Ward), The Medical College of Wisconsin, Milwaukee.

Address correspondence and reprint requests to Dr. Jerzy P. Szaflarski, University of Cincinnati Medical Center, Department of Neurology, MSB Rm. 4506, ML 525, 231 Albert B. Sabin Way, Cincinnati, OH 45267-0525; e-mail: Jerzy.Szaflarski@uc.edu

Background: It is generally accepted that most people have left-hemispheric language dominance, though the actual incidence of atypical language distribution in non–right-handed subjects has not been extensively studied. The authors examined language distribution in these subjects and evaluated the relationships between personal handedness, family history of sinistrality, and a language laterality index (LI) measured with fMRI.

Methods: The authors used whole-brain fMRI to examine 50 healthy, non–right-handed subjects (Edinburgh Handedness Inventory quotient between -100 and 52) while they performed language activation and nonlinguistic control tasks. Counts of active voxels (p < 0.001) were computed in 22 regions of interest (ROI) covering both hemispheres and the cerebellum. LI were calculated for each ROI and each entire hemisphere using the formula [L - R]/[L + R].

Results: Activation was predominantly right hemispheric in 8% (4/50), symmetric in 14% (7/50), and predominantly left hemispheric in 78% (39/50) of the subjects. Lateralization patterns were similar for all hemispheric ROI. Associations were observed between personal handedness and LI (r = 0.28, p = 0.046), family history of sinistrality and LI (p = 0.031), and age and LI (r = -0.49, p < 0.001).

Conclusions: The incidence of atypical language lateralization in normal left-handed and ambidextrous subjects is higher than in normal right-handed subjects (22% vs 4–6%). These whole-brain results confirm previous findings in a left-handed cohort studied with fMRI of the lateral frontal lobe. Associations observed between personal handedness and LI and family history of handedness and LI may indicate a common genetic factor underlying the inheritance of handedness and language lateralization.
======================
The Journal of Neuroscience, April 1, 2002, 22(7):2816-2825

Long-Term Consequences of Switching Handedness: A Positron Emission Tomography Study on Handwriting in "Converted" Left-Handers
Hartwig R. Siebner1, 2, Claus Limmer2, Alexander Peinemann2, Alexander Drzezga3, Bastiaan R. Bloem1, Markus Schwaiger3, and Bastian Conrad2
1 Sobell Department of Neurophysiology, Institute of Neurology, London WC1N 3BG, United Kingdom, and Departments of 2 Neurology and 3 Nuclear Medicine, Technical University Munich, D-81675 Munich, Germany

Until some decades ago, left-handed children who attended German schools were forced to learn to write with their right hand. To explore the long-term consequences of switching handedness, we studied the functional neuroanatomy of handwriting in 11 adult "converted" left-handers and 11 age-matched right-handers. All participants had used exclusively their right hand for writing since early childhood. Using [15O]H2O positron emission tomography, changes in normalized regional cerebral blood flow (rCBF) were assessed while participants repetitively wrote a stereotyped word with their right hand. The kinematics of handwriting did not differ between converted left-handers and right-handers. In innate right-handers, handwriting caused a preponderant left-hemispheric activation of parietal and premotor association areas. In contrast, converted left-handers demonstrated a more bilateral activation pattern with distinct activation foci in the right lateral premotor, parietal, and temporal cortex. Moreover, foci in the right rostral supplementary motor area and the right inferior parietal lobule demonstrated a positive linear relationship between the degree of "left-handedness" and normalized rCBF during right-hand writing. Functional activity in the primary sensorimotor cortex was not affected by handedness. Our findings provide evidence for persisting differences in the functional neuroanatomy of handwriting between right-handers and converted left-handers, despite decades of right-hand writing. Right-hemispheric activation in converted left-handers may reflect suppression of unwanted left-hand movements. Alternatively, this activity may represent persistent left-handedness and, as such, demonstrate a hemispheric asymmetry of hand movement representations in cortical motor association areas in relation to the direction and degree of handedness.

Key words: converted left-hander; functional brain imaging; handwriting; handedness; human; plasticity; positron emission tomography; regional cerebral blood flow
====================
Brain, Vol 120, Issue 6 1057-1065, Copyright © 1997 by Oxford University Press

The right brain hemisphere is dominant in human infants
C Chiron, I Jambaque, R Nabbout, R Lounes, A Syrota and O Dulac
Hospital F. Joliot, Department of Medical Research, Orsay, France.

The development of functional brain asymmetry during childhood is confirmed by changes in cerebral blood flow measured at rest using dynamic single photon emission computed tomography. Between 1 and 3 years of age, the blood flow shows a right hemispheric predominance, mainly due to the activity in the posterior associative area. Asymmetry shifts to the left after 3 years. The subsequent time course of changes appear to follow the emergence of functions localized initially on the right, but later on the left hemisphere (i.e. visuospatial and later language abilities). These findings support the hypothesis that, in man, the right hemisphere develops its functions earlier than the left.
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Neurology 2000;54:180
© 2000 American Academy of Neurology

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Articles

Functional anatomy of cognitive development
fMRI of verbal fluency in children and adults
W. D. Gaillard, MD, L. Hertz–Pannier, MD, PhD, S. H. Mott, MD, A. S. Barnett, PhD, D. LeBihan, MD, PhD and W. H. Theodore, MD
From the Department of Neurology (Drs. Gaillard and Mott), Children’s National Medical Center, Washington, DC; Epilepsy Research Branch (Drs. Gaillard and Theodore), National Institute of Neurologic Disorders and Stroke, NIH, Bethesda, MD; Diagnostic Radiology (Drs. Hertz–Pannier and LeBihan), Clinical Center, NIH, Bethesda, MD; and Neuroimaging Branch (Dr. Barnett), National Institute of Neurologic Disorders and Stroke, NIH, Bethesda, MD.

Address correspondence and reprint requests to Dr. William Davis Gaillard, Department of Neurology, Children’s National Medical Center, 111 Michigan Ave NW, Washington, DC 20010; e-mail: gaillardw@ninds.nih.gov

OBJECTIVE: To identify age-dependent activation patterns of verbal fluency with functional MRI (fMRI).

BACKGROUND: Few fMRI language studies have been performed in children, and none provide comparison data to adult studies. Normative data are important for interpretation of similar studies in patients with epilepsy.

METHODS: A total of 10 normal children (5 boys, 5 girls; mean age, 10.7 years; range, 8.1 to 13.1 years) and 10 normal adults (5 men, 5 women; mean age, 28.7 years; range, 19.3 to 48 years) were studied on a 1.5-T Signa MRI scanner using BOLD echo planar imaging of the frontal lobes with a verbal fluency paradigm, covert word generation to letters. Studies were analyzed with a cross-correlation algorithm (r = 0.7). A region-of-interest analysis was used to determine the extent, magnitude, and laterality of brain activation.

RESULTS: Children and adults activated similar regions, predominantly in left inferior frontal cortex (Broca’s area) and left middle frontal gyrus (dorsolateral prefrontal cortex). Children had, on average, 60% greater extent of activation than adults, with a trend for greater magnitude of activation. Children also had significantly more right hemisphere and inferior frontal gyrus activation than adults.

CONCLUSIONS: In a test of verbal fluency, children tended to activate cortex more widely than adults, but activation patterns for fluency appear to be established by middle childhood. Thus, functional MRI using verbal fluency paradigms may be applied to pediatric patient populations for determining language dominance in anterior brain regions. The greater activation found in children, including the right inferior frontal gyrus, may reflect developmental plasticity for the ongoing organization of neural networks, which underlie language capacity.

Key words: Functional MRI—Language—Verbal fluency—Children—Dominance
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Brain, Vol. 125, No. 2, 361-372, February 1, 2002
© 2002 Oxford University Press

Late plasticity for language in a child’s non-dominant hemisphere
A pre- and post-surgery fMRI study
Lucie Hertz-Pannier1,2, Catherine Chiron1,3, Isabelle Jambaqué3,5, Virginie Renaux-Kieffer3,5, Pierre-François Van de Moortele1, Olivier Delalande4, Martine Fohlen4, Francis Brunelle2 and Denis Le Bihan1
Department of Medical Research, Service Hospitalier Frederic Joliot, CEA and Institut Federatif de Recherche 49, Pediatric Radiology Department, Necker-Enfants Malades Hospital, Neuropediatric Department, Saint Vincent de Paul Hospital, Neurosurgery Department, Rothschild Foundation Hospital, Paris and U29, INSERM, Marseille, France

Correspondence to: Dr Lucie Hertz-Pannier, Pediatric Radiology Department, Necker-Enfants Malades Hospital, 149 rue de Sevres, 75015 Paris, France E-mail: lucie.hertz-pannier@nck.ap-hop-paris.fr

The ability of the right hemisphere to sustain the acquisition or the recovery of language after extensive damage to the left hemisphere has been essentially related to the age at the time of injury. Better language abilities are acquired when the insult occurs in early childhood (perinatal insults) compared with later occurrence. However, while previous studies have described the neuropsychological pattern of language development in typical cases, the neural bases of such plasticity remain unexplored. Non-invasive functional MRI (fMRI) is a unique tool to assess the neural correlates of brain plasticity through repeated studies, but the technique has not been widely used in children because of methodological limitations. Plasticity of language was studied in a boy who developed intractable epilepsy related to Rasmussen’s syndrome of the left hemisphere at age 5 years 6 months, after normal language acquisition. The first fMRI study at age 6 years 10 months showed left lateralization of language networks during a word fluency task. After left hemispherotomy at age 9 years, the child experienced profound aphasia and alexia, with rapid recovery of receptive language but slower and incomplete recovery of expressive language and reading. Postoperative fMRI at age 10 years 6 months showed a shift of language-related networks to the right during expressive and receptive tasks. Right activation was seen mainly in regions that could not be detected preoperatively, but mirrored those previously found in the left hemisphere (inferior frontal, temporal and parietal cortex), suggesting reorganization in a pre-existing bilateral network. In addition, neuropsychological data of this case support the hypothesis of innately more bilateral distribution of receptive than expressive language. This first serial fMRI study illustrates the great plasticity of the child’s brain and the ability of the right hemisphere to take over some expressive language functions, even at a relatively late age. It also suggests a limit for removal of the dominant hemisphere beyond the age of 6 years, a classical limit for the critical period of language acquisition.
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Brain, Vol 114, Issue 3 1115-1127, Copyright © 1991 by Oxford University Press

The role of the right hemisphere in emotional communication [published erratum appears in Brain 1992 Apr;115(Pt 2):645]
LX Blonder, D Bowers and KM Heilman
Department of Neurology, College of Medicine, University of Florida, Gainesville.

Previous research has established that patients with right hemisphere damage (RHD) are impaired in the comprehension of emotional prosody and facial expression. There are several explanations for this impairment. It may reflect defective acoustic and visuospatial analysis, disruption of nonverbal communicative representations, or a disturbance in the comprehension of emotional meaning. In order to examine these hypotheses, we asked RHD patients, left hemisphere damaged patients (LHD) and normal controls (NC) to judge the emotional content of sentences describing nonverbal expressions, and sentences describing emotional situations. We found that RHD subjects performed normally in their ability to infer the emotion conveyed by sentences describing situations. However, RHD patients were impaired in relation to both LHD and NC in the capacity to judge the emotional content of sentences depicting facial, prosodic, and gestural expressions, suggesting a disruption of nonverbal communicative representations.
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Neurocase (2001) Vol. 7, pp. 145-160
© Oxford University Press 2001

Hemispheric dominance for emotions, empathy and social behaviour: evidence from right and left handers with frontotemporal dementia
R. J. Perry, H. R. Rosen, J. H. Kramer, J. S. Beer,1, R. L. Levenson,1 and B. L. Miller
Memory and Aging Center, Department of Neurology, University of California, San Francisco, California and 1 Institute of Personality and Social Research, University of California, Berkeley, California, USA

Correspondence to: B. L. Miller, Memory and Aging Center, University of California, San Francisco, Suite 800, 350 Parnassus, San Francisco, CA 94143, USA. e-mail: brucem@email.his.ucsf.edu

Although evidence from primates suggests an important role for the anterior temporal cortex in social behaviour, human research has to date concentrated almost solely on the orbitofrontal cortex and amygdala. By describing four cases of the temporal variant of frontotemporal dementia we show how this degenerative condition provides an excellent model for investigating the role of the anterior temporal lobe, especially the right, in emotions, empathy and social behaviour. Assessments of semantic memory, processing of emotional facial expression and emotional prosody were made, empathy was measured, and facial expressions of emotion were coded. Of the two right handers described, one subject with predominantly left temporal lobe atrophy had severe semantic impairment but normal performance on all emotional tasks. In contrast, the subject with right temporal lobe atrophy showed severely impaired recognition of emotion from faces and voices that was not due to semantic or perceptual difficulties. Empathy was lost, interpersonal skills were severely affected and facial expression of emotion was characterized by a fixed expression that was unresponsive to situations. Additionally, two left handers with right temporal lobe atrophy are described. One demonstrated the same pattern of hemispheric lateralization as the right handers and had emotional impairment. The other left hander showed the opposite pattern of deficits, suggesting a novel presentation of anomalous dominance with reversed hemispheric specialization of semantic memory and emotional processing.
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Brain, Vol 112, Issue 1 103-111, Copyright © 1989 by Oxford University Press

Hemisphere asymmetry for eye gaze mechanisms
KJ Meador, DW Loring, GP Lee, BS Brooks, FT Nichols, EE Thompson, WO Thompson and KM Heilman
Department of Neurology, Medical College of Georgia, Augusta 30912.

To investigate left/right asymmetries in cerebral gaze mechanisms, eye deviation was evaluated in 90 patients following intracarotid sodium amylobarbitone injections. For right-handed subjects with left cerebral language dominance, the occurrence and severity of eye deviation were greater for right versus left hemisphere injections. In contrast, subjects with mixed cerebral dominance for language/handedness exhibited no left/right difference in the incidence of eye deviation. The results are consistent with right cerebral dominance for attentional/intentional mechanisms directed at external space. Further analysis suggests that the cerebral asymmetry for gaze may be due to an evolutionary loss of attentional/intentional mechanisms by the left cerebral hemisphere as language function developed.
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NeuroScience References / Further Reading

Functional Autaptic Neurotransmission in Fast-Spiking Interneurons: A Novel Form of Feedback Inhibition in the Neocortex

Volume 17, Number 16, Issue of August 15, 1997 pp. 6352-6364
Copyright ©1997 Society for Neuroscience

Massive Autaptic Self-Innervation of GABAergic Neurons in Cat Visual Cortex

Endocannabinoid-mediated short-term synaptic plasticity: depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE).

Gender difference in neural response to psychological stress

Research Articles

Prefrontal Regions Orchestrate Suppression of Emotional Memories via a Two-Phase Process

NeuroScience References / Further Reading

Functional Autaptic Neurotransmission in Fast-Spiking Interneurons: A Novel Form of Feedback Inhibition in the Neocortex

Volume 17, Number 16, Issue of August 15, 1997 pp. 6352-6364 Copyright ©1997 Society for Neuroscience

Massive Autaptic Self-Innervation of GABAergic Neurons in Cat Visual Cortex

Endocannabinoid-mediated short-term synaptic plasticity: depolarization-induced suppression of inhibition (DSI) and depolarization-induced suppression of excitation (DSE).

Gender difference in neural response to psychological stress

Research Articles

Prefrontal Regions Orchestrate Suppression of Emotional Memories via a Two-Phase Process

Volume 17, Number 16, Issue of August 15, 1997 pp. 6352-6364
Copyright ©1997 Society for Neuroscience