Orbitomedial Prefrontal Cortex Research Articles

Functional Connectivity and Coactivation of the Nucleus Accumbens: A Combined Functional Connectivity and Structure-Based Meta-analysis

This article investigates the functional connectivity patterns of the nucleus accumbens (NAcc) in 18 healthy participants using a resting state functional connectivity (rsFC) protocol. Also, a meta-analytic connectivity modeling (MACM) was used to characterize patterns of functional coactivations involving NAcc: The results of a structure-based meta-analyses of 57 fMRI and PET studies were submitted to activation likelihood estimation analysis to estimate consistent activation patterns across the different imaging studies. The results of the combined rsFC and MACM analyses show that spontaneous activity in NAcc predicts activity in regions implicated in reward circuitries, including orbitomedial prefrontal cortex, globus pallidus, thalamus, midbrain, amygdala, and insula. This confirms the key role of NAcc in the mesocorticolimbic system, which integrates inputs from limbic and cortical regions. We also detected activity in brain regions having few or no direct anatomical connections with NAcc, such as sensorimotor cortex, cerebellum, medial and posterior parietal cortex, and medial/inferior temporal cortex, supporting the view that not all functional connections can be explained by anatomical connections but can also result from connections mediated by third areas. Our rsFC findings are in line with the results of the structure-based meta-analysis: MACM maps are superimposable with NAcc rsFC results, and the reward paradigm class is the one that most frequently generates activation in NAcc. Our results overlap considerably with recently proposed schemata of the main neuron systems in the limbic forebrain and in the anterior part of the limbic midbrain in rodents and nonhuman primates.

Treatment of Apathy in Huntington’s Disease and Other Movement Disorders

Apathy is one of the most prevalent neurobehavioral symptoms in Huntington's disease (HD), occurring in approximately 70% of the symptomatic HD population. Apathy scores in patients with HD are highly correlated with duration of illness, suggesting that apathy is an inevitable consequence of advanced disease. Although less distressing than symptoms like depression and less disruptive than irritability or aggression, apathy has a considerable adverse impact on those affected with HD because it leads to a decrease of the goal-directed behaviors that contribute much to the day-to-day quality of life. As a neuropsychiatric syndrome, apathy is also common in patients with other neuropsychiatric disorders such as Parkinson's disease, traumatic brain injury, cerebrovascular accident, dementia, and other neurodegenerative conditions. The nosologic status of apathy and lack of a clear definition has probably contributed to the paucity of therapeutic evidence in this area. Several different scales are available to measure apathy, including the Apathy Evaluation Scale, Apathy Inventory, Lilles Apathy Rating Scale, and the apathy items from the Unified HD Rating Scale, the Problem Behaviours Assessment for HD, and the Neuropsychiatric Inventory, but all are based on slightly different definitions of apathy, so the scores obtained may not be directly comparable. Assessment may also be complicated by overlap between the manifestations of apathy and other complications of HD such as depression, so the identification and treatment of these comorbid conditions is important. No adequate evidence currently supports any specific pharmacologic or psychological intervention for apathy in HD. Evidence can only be extrapolated from interventional studies done in other basal ganglia disorders such as Parkinson's disease or other neurodegenerative disorders such as dementia. The neurobiology of apathy points towards three areas of functional connectivity: connections between the dorsolateral prefrontal cortex (PFC) and basal ganglia, orbitomedial PFC and basal ganglia, and dorsomedial PFC and basal ganglia. Pharmacologic interventions such as cholinesterase inhibitors, the dopaminergic antidepressant bupropion, amantadine, levodopa, bromocriptine, methylphenidate, and atypical antipsychotics have all been tried in other neurodegenerative disorders, but not in HD. Psychosocial interventions such as cognitive stimulation therapy and multisensory stimulation, which have been used in patients with dementia, have not been properly studied in HD. Individualized treatment should be considered, using a combination of methods, as there is no evidence to support one particular type of treatment. Multidisciplinary input, environmental modifications, improved psychosocial support, and psychoeducation programs designed to help caregivers to understand and compensate for the deficits caused by this symptom may all have a role to play in the treatment of apathy.

The Accumbofrontal Fasciculus in the Human Brain: A Microsurgical Anatomical Study

The fiber-dissection technique provides unique 3-dimensional anatomic knowledge of the white matter. To better identify the frontostriatal pathways in the human brain, we used a fiber-dissection technique to reconstruct neural connections between the frontal cortex and the nucleus accumbens (NAcc), which is the most ventral extent of the striatum. Thirty previously frozen, formalin-fixed human brains were dissected under the operating microscope using a modified fiber-dissection technique, primarily reported by Klingler. Our serial dissections of 30 human brain specimens clearly demonstrated that projection fibers form a connection between the NAcc and the frontal lobe. We evidenced this newly described subcortical tract as an accumbofrontal fasciculus. This focal projection was concentrated at the level of the ventromedial part of the NAcc and characterized by an elective and specific projection from the orbitomedial prefrontal cortex, particularly the gyrus rectus and the medial orbital gyrus situated between the H-shaped and the medial orbital sulcus. The accumbofrontal fasciculus is an elective and specific projection from the orbitoprefrontal cortex. This fasciculus is part of a corticostriatothalamocortical loop and a putative target for deep-brain stimulation in the treatment of obsessive-compulsive disorder and major depression. The analysis of in vivo diffusion tractography, used today as a standard in the investigation of many brain disorders, could potentially take advantage of complementary anatomic correlations and functional extrapolations, as described in this study.

Cognitive and behavioural deficits associated with the orbitomedial prefrontal cortex in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis, a progressive disease affecting motor neurons, may variably affect cognition and behaviour. We tested the hypothesis that functions associated with orbitomedial prefrontal cortex are affected by evaluating the behavioural and cognitive performance of 18 participants with amyotrophic lateral sclerosis without dementia and 18 healthy, matched controls. We measured Theory of Mind (Faux Pas Task), emotional prosody recognition (Aprosodia Battery), reversal of behaviour in response to changes in reward (Probabilistic Reversal Learning Task), decision making without risk (Holiday Apartment Task) and aberrant behaviour (Neuropsychiatric Inventory). We also assessed dorsolateral prefrontal function, using verbal and written fluency and planning (One-touch Stockings of Cambridge), to determine whether impairments in tasks sensitive to these two prefrontal regions co-occur. The patient group was significantly impaired at identifying social faux pas, recognizing emotions and decision-making, indicating mild, but consistent impairment on most measures sensitive to orbitomedial prefrontal cortex. Significant levels of aberrant behaviour were present in 50% of patients. Patients were also impaired on verbal fluency and planning. Individual subject analyses involved computing classical dissociations between tasks sensitive to different prefrontal regions. These revealed heterogeneous patterns of impaired and spared cognitive abilities: 33% of participants had classical dissociations involving orbitomedial prefrontal tasks, 17% had classical dissociations involving dorsolateral prefrontal tasks, 22% had classical dissociations between tasks of both regions, and 28% had no classical dissociations. These data indicate subtle changes in behaviour, emotional processing, decision-making and altered social awareness, associated with orbitomedial prefrontal cortex, may be present in a significant proportion of individuals with amyotrophic lateral sclerosis without dementia, some with no signs of dysfunction in tasks sensitive to other regions of prefrontal cortex. This demonstration of variability in cognitive integrity supports previous research indicating amyotrophic lateral sclerosis is a heterogeneous disease.

Age-related volumetric changes of prefrontal gray and white matter from healthy infants to adults

Event Abstract Back to Event Age-related volumetric changes of prefrontal gray and white matter from healthy infants to adults W. B. Bilker1, R. C. Gur2, M. Matsui3*, J. Matsuzawa4, T. Miyawaki4, L. Niu3, K. Noguchi5 and C. Tanaka4 1 University of Pennsylvania, Department of Biostatistics, United States 2 University of Pennsylvania, Department of Psychiatry, United States 3 University of Toyama, Department of Psychology, Japan 4 University of Toyama, Department of Pediatrics, Japan 5 University of Toyama, Department of Radiology, Japan Little is known about neuroanatomic changes in prefrontal sub-regions during human development. We evaluated prefrontal gray and white matter volume in healthy infants, children, adolescents, and adults. Magnetic resonance imaging was performed on one hundred and seven healthy people aged one month to 25 years. Gray and white matter volumes of the dorsolateral, dorsomedial, orbitolateral, orbitomedial prefrontal cortex were quantified. The results indicated that both children and early adolescents had larger dorsolateral gray matter volume than infants and adults. Dorsolateral white matter volumes of children, early adolescents, and late adolescents had larger volume than those of infants. Also, dorsomedial white matter volumes of early adolescents, late adolescents and adults had larger volume than that of infants. There was no significant difference among age group on both orbital prefrontal regions. These findings suggest there are two important stage changing structure of prefrontal cortex from infants to young adults. First, growth spurts of both gray matter and white matter during first 2 years after birth have been shown to be specifically on dorsal prefrontal cortex. Second, gray matter changes have been shown to be regionally specific, with changes in dorsal prefrontal cortex peaking during late childhood or early adolescents, but not orbital. Conference: The 20th Annual Rotman Research Institute Conference, The frontal lobes, Toronto, Canada, 22 Mar - 26 Mar, 2010. Presentation Type: Poster Presentation Topic: Frontal Lobe Development Citation: Bilker WB, Gur RC, Matsui M, Matsuzawa J, Miyawaki T, Niu L, Noguchi K and Tanaka C (2010). Age-related volumetric changes of prefrontal gray and white matter from healthy infants to adults. Conference Abstract: The 20th Annual Rotman Research Institute Conference, The frontal lobes. doi: 10.3389/conf.fnins.2010.14.00069 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Jun 2010; Published Online: 28 Jun 2010. * Correspondence: M. Matsui, University of Toyama, Department of Psychology, Toyama, Japan, miematsui@staff.kanazawa-u.ac.jp Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers W. B Bilker R. C Gur M. Matsui J. Matsuzawa T. Miyawaki L. Niu K. Noguchi C. Tanaka Google W. B Bilker R. C Gur M. Matsui J. Matsuzawa T. Miyawaki L. Niu K. Noguchi C. Tanaka Google Scholar W. B Bilker R. C Gur M. Matsui J. Matsuzawa T. Miyawaki L. Niu K. Noguchi C. Tanaka PubMed W. B Bilker R. C Gur M. Matsui J. Matsuzawa T. Miyawaki L. Niu K. Noguchi C. Tanaka Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Emotional feeling and the orbitomedial prefrontal cortex: Theoretical and empirical considerations

Emotional feeling can be defined as the affective constituent of emotions representing a subjective experience such as, for example, feeling love or hate. Several recent neuroimaging studies have focused on this affective component of emotions thereby aiming to characterise the underlying neural correlates. These studies indicate that the orbitomedial prefrontal cortex is crucially involved in the processing of emotional feeling. It is the aim of this paper to analyse the extent to which the present state of the art in neuroscience enables emotional feeling to be related to specific brain regions. In the first step, methodological and theoretical problems in the investigation of emotional feeling will be discussed leading to the characterisation of a “twofold gap.” This gap represents (a) the theoretical difficulties encountered in transforming vivid subjective experience into a theoretical psychological concept, and (b) the problems of implementing such a concept by performing empirical studies. Based on these considerations we suggest approaches for future empirical studies. In the second step, a group of functional neuroimaging studies focusing on the affective constituent of emotions will be discussed in detail with regard to the theoretical problems outlined in the first step.

Abnormal Amygdala-Prefrontal Effective Connectivity to Happy Faces Differentiates Bipolar from Major Depression

Bipolar disorder is frequently misdiagnosed as major depressive disorder, delaying appropriate treatment and worsening outcome for many bipolar individuals. Emotion dysregulation is a core feature of bipolar disorder. Measures of dysfunction in neural systems supporting emotion regulation might therefore help discriminate bipolar from major depressive disorder. Thirty-one depressed individuals-15 bipolar depressed (BD) and 16 major depressed (MDD), DSM-IV diagnostic criteria, ages 18-55 years, matched for age, age of illness onset, illness duration, and depression severity-and 16 age- and gender-matched healthy control subjects performed two event-related paradigms: labeling the emotional intensity of happy and sad faces, respectively. We employed dynamic causal modeling to examine significant among-group alterations in effective connectivity (EC) between right- and left-sided neural regions supporting emotion regulation: amygdala and orbitomedial prefrontal cortex (OMPFC). During classification of happy faces, we found profound and asymmetrical differences in EC between the OMPFC and amygdala. Left-sided differences involved top-down connections and discriminated between depressed and control subjects. Furthermore, greater medication load was associated with an amelioration of this abnormal top-down EC. Conversely, on the right side the abnormality was in bottom-up EC that was specific to bipolar disorder. These effects replicated when we considered only female subjects. Abnormal, left-sided, top-down OMPFC-amygdala and right-sided, bottom-up, amygdala-OMPFC EC during happy labeling distinguish BD and MDD, suggesting different pathophysiological mechanisms associated with the two types of depression.

Elevated Left and Reduced Right Orbitomedial Prefrontal Fractional Anisotropy in Adults With Bipolar Disorder Revealed by Tract-Based Spatial Statistics

Diffusion tensor imaging (DTI) studies in adults with bipolar disorder (BD) indicate altered white matter (WM) in the orbitomedial prefrontal cortex (OMPFC), potentially underlying abnormal prefrontal corticolimbic connectivity and mood dysregulation in BD. To use tract-based spatial statistics (TBSS) to examine WM skeleton (ie, the most compact whole-brain WM) in subjects with BD vs healthy control subjects. Cross-sectional, case-control, whole-brain DTI using TBSS. University research institute. Fifty-six individuals, 31 having a DSM-IV diagnosis of BD type I (mean age, 35.9 years [age range, 24-52 years]) and 25 controls (mean age, 29.5 years [age range, 19-52 years]). Fractional anisotropy (FA) longitudinal and radial diffusivities in subjects with BD vs controls (covarying for age) and their relationships with clinical and demographic variables. Subjects with BD vs controls had significantly greater FA (t > 3.0, P <or= .05 corrected) in the left uncinate fasciculus (reduced radial diffusivity distally and increased longitudinal diffusivity centrally), left optic radiation (increased longitudinal diffusivity), and right anterothalamic radiation (no significant diffusivity change). Subjects with BD vs controls had significantly reduced FA (t > 3.0, P <or= .05 corrected) in the right uncinate fasciculus (greater radial diffusivity). Among subjects with BD, significant negative correlations (P < .01) were found between age and FA in bilateral uncinate fasciculi and in the right anterothalamic radiation, as well as between medication load and FA in the left optic radiation. Decreased FA (P < .01) was observed in the left optic radiation and in the right anterothalamic radiation among subjects with BD taking vs those not taking mood stabilizers, as well as in the left optic radiation among depressed vs remitted subjects with BD. Subjects having BD with vs without lifetime alcohol or other drug abuse had significantly decreased FA in the left uncinate fasciculus. To our knowledge, this is the first study to use TBSS to examine WM in subjects with BD. Subjects with BD vs controls showed greater WM FA in the left OMPFC that diminished with age and with alcohol or other drug abuse, as well as reduced WM FA in the right OMPFC. Mood stabilizers and depressed episode reduced WM FA in left-sided sensory visual processing regions among subjects with BD. Abnormal right vs left asymmetry in FA in OMPFC WM among subjects with BD, likely reflecting increased proportions of left-sided longitudinally aligned and right-sided obliquely aligned myelinated fibers, may represent a biologic mechanism for mood dysregulation in BD.

Subcortical Gray Matter Volume Abnormalities in Healthy Bipolar Offspring: Potential Neuroanatomical Risk Marker for Bipolar Disorder?

A growing number of structural neuroimaging studies have shown that bipolar disorder (BD) is associated with gray matter (GM) volume abnormalities in brain regions known to support affect regulation. The goal of this study was to examine whole-brain regional GM volume in healthy bipolar offspring (HBO) relative to age-matched controls to identify possible structural abnormalities that may be associated with risk for BD. Participants were 20 youths (8-17 years old) with at least one parent diagnosed with BD, and 22 age-matched healthy individuals. All of them were free of Axis I diagnoses. High-resolution magnetic resonance imaging structural images were acquired using a 3-T Siemens scanner. Voxel-based morphometric analyses were conducted using SPM5. Relative to controls, HBO had significantly increased GM volume in left parahippocampal/hippocampal gyrus (p <.05 corrected), following whole-brain analyses. This increase was correlated with puberty but not age in HBO. Region-of-interest analyses on the amygdala and orbitomedial prefrontal cortex did not yield any significant group differences after conducting small volume correction. The pattern of increased GM volume in parahippocampal/hippocampal gyrus in HBO suggests a potential marker for risk for BD. It can also be considered as a potential neuroprotective marker for the disorder because HBO were free of current psychopathology. Prospective studies examining the relationship between changes in GM volume in these regions and subsequent development of BD in HBO will allow us to elucidate further the role of this region in either conferring risk for or protecting against the development of BD.

Borderline Personality Disorder Demystified: An Essential Guide for Understanding and Living With BPD

Back to table of contents Previous article Next article Book ReviewFull AccessBorderline Personality Disorder Demystified: An Essential Guide for Understanding and Living With BPDSusan E. Bailey M.D.Susan E. Bailey M.D.Search for more papers by this authorPublished Online:1 Mar 2007https://doi.org/10.1176/ps.2007.58.3.422AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Robert Friedel wrote this admirable book primarily for individuals who suffer from borderline personality disorder. In doing so, however, he renders a valuable service to the rest of us—the loved ones, family members, and treatment teams of people with this disabling condition. While reading his book, I squirmed with chagrin, realizing how often I've rolled my eyes, grimaced, and explained to my residents a patient's latest annoying exploit with the dismissive phrase, "She's a borderline!" I need to develop—and inculcate in my students—the understanding, patience, clarity, and hopefulness of Dr. Friedel.I will no doubt do everyone more good by emphasizing the author's most insistent point: the impulsive, self-destructive behaviors and frantic manipulations of these patients arise less from willfulness than from impaired neurotransmitter activity, brain dysfunction along important neural pathways, and learned, maladaptive behaviors that substitute for flexible coping skills.Friedel dedicates his book to his sister, Denise, who suffered from borderline personality disorder. She died much too early from one of the common complications and comorbidities of her disease. And there are many—substance abuse, mood disorders, eating disorders, panic attacks, and posttraumatic stress disorder. He thus brings to his book not only the voice of the psychiatric researcher and clinician—he is distinguished clinical professor of psychiatry at Virginia Commonwealth University and professor emeritus at the University of Alabama at Birmingham—but also the voice of family and relationship. He knows intimately the frustration and anger that family members can feel in relation to the person with borderline personality disorder, but he has also focused an impressive career upon the biology of this disorder and the most effective treatments, particularly pharmacologic ones.Friedel organizes his book, initially created as a series of handouts for his patients and their families, in such a way that one can skip about easily among topics of special interest, such as medications, psychotherapies, and symptoms. Nevertheless, if reading the book straight through, one discovers that Friedel carefully lays the groundwork for understanding both the symptoms—emotional storms, impulsivity, and bizarre or paranoid reasoning and perceptions—and the pharmacologic treatment—primarily selective serotonin reuptake inhibitors, low-dose neuroleptics, and mood stabilizers—of the disorder by describing impaired brain function in the amygdala, the anterior cingulate and orbitomedial prefrontal cortex, and the dorsolateral prefrontal cortex. None of his reports of research findings is footnoted within his text, but he supplies a bibliography keyed to each chapter at the end of his book.Although Friedel devotes more of his text to pharmacologic treatments, he doesn't overlook the importance of therapy and the multiple types that can be useful, including dialectical behavior therapy, interpersonal group therapy, and individual supportive therapy. He maintains an optimistic outlook on both treatment fronts. As our understanding of brain chemistry and neural systems deepens, so will our ability to target more accurately and effectively our pharmacologic and therapeutic interventions.Friedel's compassion, wisdom, and skillful writing result in a highly readable, useful book for patients, families, and providers.Dr. Bailey is an instructor in psychiatry at the Johns Hopkins University School of Medicine, Baltimore. FiguresReferencesCited byDetailsCited ByNone Volume 58Issue 3 March, 2007Pages 422-423PSYCHIATRIC SERVICES March 2007 Volume 58 Number 3 Metrics PDF download History Published online 1 March 2007 Published in print 1 March 2007

Angels, Devils, and Censors in the Brain

How is the human brain organized to enhance or suppress specifi c types of behavior? Can we provide a biological explanation for differences between individuals (and societies) in the behaviors they enhance or suppress? Insights from social neuroscience, brain imaging, and neural network theory suggest which cortical-subcortical interactions subserve enhancing or suppressing classes of behaviors. The brain networks proposed for these functions connect four previous research streams from different disciplines. The fi rst stream is Eisler and Levine’s construction of three separate brain networks for the confl icting behavior patterns of fior fldissociation, and bonding – with the orbitomedial prefrontal cortex playing a crucial role in selecting among these patterns. The second is Newman, Grace, O’Reilly, and others’ work on motor ‘gates’ (in the basal ganglia) infl uenced by contextual signals (from the hippocampus) and/or affective signals (from the amygdala). The third is Cloninger’s clinical schema for interacting character and temperament dimensions of personality, which in

Amygdalar and prefrontal pathways to the lateral hypothalamus are activated by a learned cue that stimulates eating.

Experimental animals that are trained to associate a cue with food consumption when hunger prevails will subsequently consume a greater amount of food when that cue is presented under conditions of satiety. Previously, we showed that this phenomenon of conditioned potentiation of feeding is abolished by a neurotoxic lesion that encompasses the basolateral (BL), basomedial (BM), and lateral (LA) nuclei of the amygdala (AMY) and by disconnection of this region and lateral hypothalamus (LHA). Here, we combined immediate-early gene (IEG) and tract-tracing methods to map functional AMY-LHA circuitry that is engaged when potentiated feeding is produced by pavlovian conditioning. Sated rats were assessed for food consumption in the presence of a cue that was paired previously with food (CS+), or in the presence of another cue that was never paired with food (CS-), in two consecutive tests temporally arranged for activation of the effector IEGs Arc (activity-regulated cytoskeletal protein) and Homer 1a. We examined the selective induction of the IEGs by tests with CS+ or CS- presentations in AMY neurons that project to LHA, as identified with the retrograde tracer FluoroGold. Using the same labeling methods, we also examined neurons in several other forebrain regions, including the prefrontal cortex and nucleus accumbens, that receive strong inputs from BL/BM/LA nuclei and, in turn, innervate the LHA. Our results indicate that a cue that has acquired the ability to promote eating in sated rats (CS+) strongly activates a functional network formed by direct pathways from the BL/BM and orbitomedial prefrontal cortex to the LHA.

Biting Behavior, Aggression, and Seizures

To describe the semiologic features of aggressive behaviors observed in human epileptic seizures with particular reference to the act of biting a conspecific. We analyzed the biting behavior (BB) and other aggressive gestures occurring in a group of 11 patients retrospectively selected from >1,000 patients subjected to video-EEG/SEEG monitoring for presurgical evaluation of drug-resistant seizures. Patients displaying BB showed (a) a male sex predominance, (b) heterogeneous etiologies and lesion locations, and (c) seizures involving the frontotemporal regions of both hemispheres. The act of biting was a rapid motor action, lasting approximately 600 ms, occurring in the context of strong emotional arousal, fear, and anger, with various bodily gestures with aggressive connotation. BB was mainly a "reflexive" behavior, in that biting acts were evoked (both during and after seizures) by actions of people in close contact with the patient. The sole intrusion of the examiner's hand in the space near the patient's face was effective in triggering BB. Rarely, self-directed or object-directed biting acts were not triggered by external stimuli. Intracranial data (SEEG) obtained in one subject showed that the amygdala/hippocampal region plus the orbitomedial prefrontal cortex had to be involved by ictal activity to observe BB. Anatomic and electrophysiologic data in our patients suggest that a model of dual--temporal and frontal--dysfunction could account for the occurrence of ictal/postictal BB. Behavioral data suggest also that BB and related aggressive gestures can be considered as the emergence of instinctive behaviors with an adaptative significance of defense of the peripersonal space.

Voxel-based morphometry and stereology provide convergent evidence of the importance of medial prefrontal cortex for fluid intelligence in healthy adults

We investigated whether a relationship exists between frontal lobe volume and fluid intelligence as measured by both Cattell's Culture Fair test and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Performance scale, but not with crystallized intelligence as measured by the WAIS-R Verbal scale, in healthy adults, using two well-established image analysis techniques applied to high-resolution MR brain images. Firstly, using voxel-based morphometry (VBM), we investigated whether a significant relationship exists between gray matter concentration and fluid intelligence on a voxel-by-voxel basis. Secondly, we applied the Cavalieri method of modern design stereology in combination with point counting to investigate possible relationships between macroscopic volumes of relevant brain regions defined as dorsolateral, dorsomedial, orbitolateral, and orbitomedial prefrontal cortex on the basis of neuroanatomical landmarks, and fluid intelligence. We also examined the effect on these relationships of normalizing regional brain volumes to intracranial volume. VBM analysis revealed a positive correlation between gray matter concentration in the medial region of prefrontal cortex and Culture Fair scores (corrected for multiple comparisons), and also WAIS-R Performance Intelligence sum of scaled scores (SSS) (uncorrected for multiple comparisons before controlling for age, and this converges with the stereological finding of the positive correlation between volume of dorsomedial prefrontal cortex normalized to intracranial volume and Culture Fair scores after controlling for age. WAIS-R Verbal Intelligence SSS showed no correlations. We interpret our findings, from independent analyses of both VBM and stereology, as evidence of the importance of medial prefrontal cortex in supporting fluid intelligence.

Gender-Moderated Dorsolateral Prefrontal Reductions in 22q11.2 Deletion Syndrome: Implications for Risk for Schizophrenia

To investigate the impact of the microdeletion on morphology of the prefrontal cortex in 22q11.2 Deletion Syndrome (22q11.2 DS), high-resolution, anatomic magnetic resonance imaging was performed on 19 children and adolescents with 22q11.2 DS (11 females, 8 males) and 18 unaffected controls (10 females, 8 males). Tissue volumes of the dorsolateral, dorsomedial, orbitolateral, and orbitomedial prefrontal cortex were measured. Tasks of executive function and working memory were administered to investigate the association between anatomy and function. Whole brain volume and frontal lobe tissue volume were preserved in girls but reduced in boys with 22q11.2 DS relative to age-matched controls. Dorsolateral prefrontal cortex (DLPFC) volumes were reduced in participants with 22q11.2 DS, although the gender-by-diagnosis effect found for frontal lobe was not as robust for DLPFC. DLPFC volumes were associated with performance on tasks of planning and emotional facial recognition. Longitudinal studies are needed to clarify whether gender differences in frontal lobe and DLPFC persist with development, and whether the volumes of the DLPFC are associated with eventual deterioration in adaptive/psychosocial function that may presage the onset of schizophrenia, for which individuals with 22q11.2 DS are at a disproportionately high risk.

Afferent projections to nucleus reuniens of the thalamus

The nucleus reuniens (RE) is the largest of the midline nuclei of the thalamus and the major source of thalamic afferents to the hippocampus and parahippocampal structures. Nucleus reuniens has recently been shown to exert powerful excitatory actions on CA1 of the hippocampus. Few reports on any species have examined afferent projections to nucleus reuniens. By using the retrograde anatomical tracer Fluorogold, we examined patterns of afferent projections to RE in the rat. We showed that RE receives a diverse and widely distributed set of afferents projections. The main sources of input to nucleus reuniens were from the orbitomedial, insular, ectorhinal, perirhinal, and retrosplenial cortices; CA1/subiculum of hippocampus; claustrum, tania tecta, lateral septum, substantia innominata, and medial and lateral preoptic nuclei of the basal forebrain; medial nucleus of amygdala; paraventricular and lateral geniculate nuclei of the thalamus; zona incerta; anterior, ventromedial, lateral, posterior, supramammillary, and dorsal premammillary nuclei of the hypothalamus; and ventral tegmental area, periaqueductal gray, medial and posterior pretectal nuclei, superior colliculus, precommissural/commissural nuclei, nucleus of the posterior commissure, parabrachial nucleus, laterodorsal and pedunculopontine tegmental nuclei, nucleus incertus, and dorsal and median raphe nuclei of the brainstem. The present findings of widespread projections to RE, mainly from limbic/limbic-associated structures, suggest that nucleus reuniens represents a critical relay in the transfer of limbic information (emotional/cognitive) from RE to its major targets, namely, to the hippocampus and orbitomedial prefrontal cortex. RE appears to be a major link in the two-way exchange of information between the hippocampus and the medial prefrontal cortex.

The legacy of the silver methods and the new anatomy of the basal forebrain: implications for neuropsychiatry and drug abuse.

The first part of the paper highlights the remarkable legacy of the silver methods, with special emphasis on the travails and opportunities offered by the various Nauta methods and their modifications. When the tracer methods based on axoplasmic flow were introduced in the early 1970s, they were exploited on a backdrop of a basic anatomical framework, which had already been established through the tracing of the major CNS pathways by the aid of the silver methods, especially the widely used Nauta-Gygax methods and their modifications. Some of the silver methods that were developed in the late 1960s for the staining of degenerating boutons (e.g. the Fink-Heimer method and de Olmos cupric silver method) provided the necessary technical improvements that eventually led to a new and more productive way to look at the basal forebrain functional/anatomical organization; if it was not for the silver methods, we would in all likelihood still be promoting the nebulous notion of the substantia innominata rather than the concepts of the ventral striatopallidal system and the extended amygdala. The discovery and elaboration of these two macroanatomical systems symbolize what might deservedly be called the "new anatomy" of the basal forebrain. Following a review of the critical experiments which led to the development of the new anatomy of the basal forebrain, its topography in the human is reviewed in drawings of an abbreviated series of coronal sections. The discovery of the ventral striatopallidal system and its thalamic projection to the mediodorsal thalamus rather than to the ventral anterior-ventral lateral thalamic complex ushered in the idea of parallel cortico-subcortical reentrant circuits, which to a large extent has replaced the limbic system as a theoretical framework for neuropsychiatric disorders. The extended amygdala, which appears as a large ring formation around the internal capsule, is still controversial in some quarters, although it is slowly but surely making its way into the general neuroscience literature, especially in the field of addictive disorders. The ventral striatopallidal system and the extended amygdala are interwoven in a complex fashion with the basal nucleus of Meynert within the basal forebrain. Together, these three systems represent important output channels for so-called "limbic" forebrain regions, especially orbitomedial prefrontal cortex and medial temporal lobe structures, which are increasingly implicated in major neuropsychiatric disorders.

Nurture, Nature, and Caring: We Are Not Prisoners of Our Genes

This article develops a theory for how caring behavior fits into the makeup of humans and other mammals. Biochemical evidence for three major patterns of response to stressful or other- wise complex situations is reviewed. There is the classic fight-or-flight response; the dissociative response, involving emotional withdrawal and disengagement; and the bonding response, a variant of which Taylor et al. (2000) called tend-and-befriend. All three of these responses can be explained as adaptations that have been selected for in evolution and are shared between humans and other mammals. Yet each of us contains varying tendencies toward all of these responses. How does development interact with genes to influence these tendencies? How do individuals, societies, and institutions make choices between these types of responses? We review the evidence, based on beha- vioral, lesion, single-cell, and brain imaging studies, for cortical-subcortical interactions involved in all three of these response types, and propose partial neural network models for some of these interactions. We propose that the orbitomedial prefrontal cortex mediates this choice process. This area of prefrontal cortex performs this mediation through its connections with areas of sensory and association cortex that represent social contexts or stimuli, and with areas of the hypothalamus, limbic system, and autonomic nervous system that represent emotional states or classes of response patterns. The article concludes with implications of our theory for social interactions and institutions. We argue that despite the wide prevalence of fight-or-flight responses, the bonding, caring responses remain available. We show with historical and contemporary examples how social settings - whether in education, work places, families, politics, and informal social customs - can be designed to support and enhance the natural caring responses of the brain.

The hippocampal formation — orbitomedial prefrontal cortex circuit in the attentional control of active memory

The long held view that the hippocampal formation is not only essential, but also solely responsible for declarative memory in humans (and by analogy non-human primates) has come into question. Based on extensive reciprocal connection patterns between the hippocampal formation and the orbitoventromedial prefrontal cortex in primates and rats, a central role for the hippocampal formation in the attentional control of behavior is emerging. In this paper, evidence is reviewed showing that the hippocampal–orbitomedial prefrontal cortex circuit may be involved in attentional monitoring of the internal sensorium. This attentional monitoring system, in a sense, is the working memory of viscero-emotional processing. The hippocampal formation can thus be viewed as a discrepancy detector with respect to the relative activational status of cognitive/emotional set in the orbitomedial prefrontal cortex. Discrepencies between the current representation of the internal milieu and the ‘just-prior’ representation held ‘on-line’ in orbitomedial prefrontal cortex associative working memory, are signaled from the hippocampus to the prefrontal cortex prospective attentional systems to activate, process, and reconcile internal (past) with external (present) environments, and finally to effectively alter active working emotional ‘sets’ to exert cognitive–emotional control of behavior.

Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia.

Converging neuroanatomic, neurophysiological, and neurobehavioral evidence implicate prefrontal subregions in schizophrenia. Neuroanatomic studies with magnetic resonance (MR) imaging enable regional volume parcellation. Inconsistent reports may relate to variable methods and small samples. We attempted to resolve volume differences within sectors of the prefrontal lobe in a large sample, relating volumes to clinical and neurocognitive features. Magnetic resonance imaging was performed in 70 patients with schizophrenia (40 men and 30 women; 29 neuroleptic naive and 41 previously treated) and 81 healthy controls (34 men and 47 women). Gray and white matter volumes of the dorsolateral, dorsomedial, orbitolateral, and orbitomedial prefrontal cortex were quantified. Symptoms, functioning, and neurocognition were assessed concurrently. Reduced prefrontal gray matter volume was observed in patients. The reduction was evident for the dorsolateral area in men (9%) and women (11%), for the dorsomedial area only in men (9%), and for orbital regions only in women (23% and 10% for lateral and medial, respectively). The reduction of orbital volume in women was associated with poorer premorbid functioning, more severe negative symptoms, and depression. Volume of dorsal cortex was positively associated with better performance on abstraction and attention tasks across all groups. Schizophrenia is associated with reduced gray matter volume in prefrontal cortex, which affects men and women in the dorsolateral sector. The effects are moderated by sex for dorsomedial and orbital regions and are related to symptom severity and cognitive function. This is not a by-product of treatment, since the differences are evident in neuroleptic-naive patients.