Expression of the mRNAs encoding the limbic system-associated membrane protein (LAMP): II. Fetal rat brain.

PubMed

Pimenta, A F; Reinoso, B S; Levitt, P

1996-11-11

The limbic system-associated membrane protein (LAMP) is a 64-68 kDa neuronal surface glycoprotein expressed in cortical and subcortical regions of the limbic system of the adult and developing rat central nervous system (CNS). LAMP is a member of the immunoglobulin superfamily of cell adhesion molecules with three Ig domains and is highly conserved between rat and human. In this study, the temporal and spatial pattern of lamp gene expression during fetal rat development was analyzed by using Northern blot analysis and in situ hybridization. In Northern blot analysis, two lamp mRNA transcripts, 1.6 kb and 8.0 kb, identical in size to those present in the adult rat nervous system, were detected in developing neural tissue. In situ hybridization analysis showed close correlation, though not identity, between the expression of lamp mRNAs and the distribution of LAMP in limbic regions of the developing rat CNS, indicative of a more complex regulation of gene expression than was previously thought to be the case. The expression of lamp mRNAs is first detected on about embryonic day (E) 13. The hybridization signal is not seen in the proliferative ventricular zone at any level of the neuraxis, indicating that lamp is expressed in postmitotic neurons. In the cerebral cortex, lamp mRNAs are expressed in limbic cortical regions, such as the perirhinal cortex, prefrontal cortex, and cingulate cortex. In the hippocampus, the hybridization signal is observed in Ammon's horn by E18. The neostriatum, amygdaloid complex, and most hypothalamic areas express lamp mRNAs from early stages (E13-E14) in a pattern consistent with the onset of neurogenesis. The emerging patterns of lamp expression at the outset are similar to those seen in adult hypothalamus and dorsal thalamus. Although the hybridization signal is observed in some nonlimbic areas, including midbrain and hindbrain structures, intense labeling is evident in more classic limbic regions. The high levels of expression of lamp in limbic regions, beginning in early developmental stages, combined with the results of previous functional in vitro and in vivo studies, support a role for LAMP as a recognition molecule involved in the formation of limbic connections.

Long-Term Effects of Acute Stress on the Prefrontal-Limbic System in the Healthy Adult

PubMed Central

Wei, Dongtao; Du, Xue; Zhang, Qinglin; Liu, Guangyuan; Qiu, Jiang

2017-01-01

Most people are exposed to at least one traumatic event during the course of their lives, but large numbers of people do not develop posttraumatic stress disorders. Although previous studies have shown that repeated and chronic stress change the brain’s structure and function, few studies have focused on the long-term effects of acute stressful exposure in a nonclinical sample, especially the morphology and functional connectivity changes in brain regions implicated in emotional reactivity and emotion regulation. Forty-one months after the 5/12 Wenchuan earthquake, we investigated the effects of trauma exposure on the structure and functional connectivity of the brains of trauma-exposed healthy individuals compared with healthy controls matched for age, sex, and education. We then used machine-learning algorithms with the brain structural features to distinguish between the two groups at an individual level. In the trauma-exposed healthy individuals, our results showed greater gray matter density in prefrontal-limbic brain systems, including the dorsal anterior cingulate cortex, medial prefrontal cortex, amygdala and hippocampus, than in the controls. Further analysis showed stronger amygdala-hippocampus functional connectivity in the trauma-exposed healthy compared to the controls. Our findings revealed that survival of traumatic experiences, without developing PTSD, was associated with greater gray matter density in the prefrontal-limbic systems related to emotional regulation. PMID:28045980

Reduced hippocampal and parahippocampal volumes in murderers with schizophrenia.

PubMed

Yang, Yaling; Raine, Adrian; Han, Chen-Bo; Schug, Robert A; Toga, Arthur W; Narr, Katherine L

2010-04-30

Evidence has accumulated to suggest that individuals with schizophrenia are at increased risk for violent offending. Furthermore, converging evidence suggests that abnormalities in the fronto-limbic system, including the prefrontal cortex, the hippocampus, and the parahippocampal gyrus, may contribute towards both neuropsychological disturbances in schizophrenia and violent behavior. Since the behavioral and clinical consequences of disturbed fronto-limbic circuitry appear to differ in schizophrenia and violence, it may be argued that patients with schizophrenia who exhibit violent behavior would demonstrate different structural abnormalities compared to their non-violent counterparts. However, the neurobiological basis underlying homicide offenders with schizophrenia remains unclear and little is known regarding the cross-cultural applicability of the findings. Using a 2 x 2 factorial design on a total Chinese sample of 92 males and females, we found reduced gray matter volume in the hippocampus and parahippocampal gyrus in murderers with schizophrenia, in the parahippocampal gyrus in murderers without schizophrenia, and in the prefrontal cortex in non-violent schizophrenia compared to normal controls. Results provide initial evidence demonstrating cross-cultural generalizability of prior fronto-limbic findings on violent schizophrenia. Future studies examining subtle morphological changes in frontal and limbic structures in association with clinical and behavioral characteristics may help further clarify the neurobiological basis of violent behavior. Copyright @ 2009 Elsevier Ireland Ltd. All rights reserved.

Reduced hippocampal and parahippocampal volumes in murderers with schizophrenia

PubMed Central

Raine, Adrian; Han, Chen-Bo; Schug, Robert A.; Toga, Arthur W.; Narr, Katherine L.

2010-01-01

Evidence has accumulated to suggest that individuals with schizophrenia are at increased risk for violent offending. Furthermore, converging evidence suggests that abnormalities in the fronto-limbic system, including the prefrontal cortex, hippocampus, and the parahippocampal gyrus, may contribute towards both neuropsychological disturbances in schizophrenia and violent behavior. Since the behavioral and clinical consequences of disturbed fronto-limbic circuitry appear to differ in schizophrenia and violence, it may be argued that patients with schizophrenia who exhibit violent behavior would demonstrate different structural abnormalities compared to their non-violent counterparts. However, the neurobiological basis underlying homicide offenders with schizophrenia remains unclear and little is known regarding the cross-cultural applicability of the findings. Using a 2 × 2 factorial design on a total Chinese sample of 92 males and females, we found reduced gray matter volume in the hippocampus and parahippocampal gyrus in murderers with schizophrenia, in the parahippocampal gyrus in murderers without schizophrenia, and in the prefrontal cortex in non-violent schizophrenia compared to normal controls. Results provide initial evidence demonstrating cross-cultural generalizability of prior fronto-limbic findings on violent schizophrenia. Future studies examining subtle morphological changes in frontal and limbic structures in association with clinical and behavioral characteristics may help further clarify the neurobiological basis of violent behavior. PMID:20227253

Descending motor pathways and the spinal motor system - Limbic and non-limbic components

NASA Technical Reports Server (NTRS)

Holstege, Gert

1991-01-01

Research on descending motor pathways to caudal brainstem and spinal cord in the spinal motor system is reviewed. Particular attention is given to somatic and autonomic motoneurons in the spinal cord and brainstem, local projections to motoneurons, bulbospinal interneurons projecting to motoneurons, descending pathways of somatic motor control systems, and descending pathways involved in limbic motor control systems.

Neurocircuitry of limbic dysfunction in anorexia nervosa.

PubMed

Lipsman, Nir; Woodside, D Blake; Lozano, Andres M

2015-01-01

Anorexia Nervosa (AN) is a serious psychiatric condition marked by firmly entrenched and maladaptive behaviors and beliefs about body, weight and food, as well as high rates of psychiatric comorbidity. The neural roots of AN are now beginning to emerge, and appear to be related to dysfunctional, primarily limbic, circuits driving pathological thoughts and behaviors. As a result, the significant physical symptoms of AN are increasingly being understood at least partially as a result of abnormal or dysregulated emotional processing. This paper reviews the nature of limbic dysfunction in AN, and how structural and functional imaging has implicated distinct emotional and perceptual neural circuits driving AN symptoms. We propose that top-down and bottom-up influences converge on key limbic modulatory structures, such as the subcallosal cingulate and insula, whose normal functioning is critical to affective regulation and emotional homeostasis. Dysfunctional activity in these structures, as is seen in AN, may lead to emotional processing deficits and psychiatric symptoms, which then drive maladaptive behaviors. Modulating limbic dysregulation may therefore be a potential treatment strategy in some AN patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Multimodal Neuroimaging of Fronto-limbic Structure and Function Associated with Suicide Attempts in Adolescents and Young Adults with Bipolar Disorder

PubMed Central

Johnston, Jennifer A. Y.; Wang, Fei; Liu, Jie; Blond, Benjamin N.; Wallace, Amanda; Liu, Jiacheng; Spencer, Linda; Cox Lippard, Elizabeth T.; Purves, Kirstin L.; Landeros-Weisenberger, Angeli; Hermes, Eric; Pittman, Brian; Zhang, Sheng; King, Robert; Martin, Andrés; Oquendo, Maria A.; Blumberg, Hilary P.

2018-01-01

Objective Bipolar disorder is associated with high risk for suicide behavior that often develops in adolescence/young adulthood. Elucidation of involved neural systems is critical for prevention. This study of adolescents/young adults with bipolar disorder with and without history of suicide attempts combines structural, diffusion tensor and functional magnetic resonance imaging methods to investigate implicated abnormalities in structural and functional connectivity within fronto-limbic systems. Method Participants with bipolar disorder included 26 with a prior suicide attempt and 42 without attempts. Regional gray matter volume, white matter integrity and functional connectivity during processing of emotional stimuli were compared between groups and differences were explored for relationships between imaging modalities and associations with suicide-related symptoms and behaviors. Results Compared to the non-attempter group, the attempter group showed reductions in gray matter volume in orbitofrontal cortex, hippocampus and cerebellum; white matter integrity in uncinate fasciculus, ventral frontal and right cerebellum regions; and amygdala functional connectivity to left ventral and right rostral prefrontal cortex (p<0.05, corrected). In exploratory analyses, among attempters, right rostral prefrontal connectivity was negatively correlated with suicidal ideation (p<0.05), and left ventral prefrontal connectivity was negatively correlated with attempt lethality (p<0.05). Conclusions Adolescent/young adult suicide attempters with bipolar disorder demonstrate less gray matter volume and decreased structural and functional connectivity in a ventral fronto-limbic neural system subserving emotion regulation. Among suicide attempters, reductions in amygdala-prefrontal functional connectivity may be associated with severity of suicide ideation and attempt lethality. PMID:28135845

Bidirectional Causal Connectivity in the Cortico-Limbic-Cerebellar Circuit Related to Structural Alterations in First-Episode, Drug-Naive Somatization Disorder

PubMed Central

Li, Ranran; Liu, Feng; Su, Qinji; Zhang, Zhikun; Zhao, Jin; Wang, Ying; Wu, Renrong; Zhao, Jingping; Guo, Wenbin

2018-01-01

Background: Anatomical and functional deficits in the cortico-limbic-cerebellar circuit are involved in the neurobiology of somatization disorder (SD). The present study was performed to examine causal connectivity of the cortico-limbic-cerebellar circuit related to structural deficits in first-episode, drug-naive patients with SD at rest. Methods: A total of 25 first-episode, drug-naive patients with SD and 28 healthy controls underwent structural and resting-state functional magnetic resonance imaging. Voxel-based morphometry and Granger causality analysis (GCA) were used to analyze the data. Results: Results showed that patients with SD exhibited decreased gray matter volume (GMV) in the right cerebellum Crus I, and increased GMV in the left anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), and left angular gyrus. Causal connectivity of the cortico-limbic-cerebellar circuit was partly affected by structural alterations in the patients. Patients with SD showed bidirectional cortico-limbic connectivity abnormalities and bidirectional cortico-cerebellar and limbic-cerebellar connectivity abnormalities. The mean GMV of the right MFG was negatively correlated with the scores of the somatization subscale of the symptom checklist-90 and persistent error response of the Wisconsin Card Sorting Test (WCST) in the patients. A negative correlation was observed between increased driving connectivity from the right MFG to the right fusiform gyrus/cerebellum IV, V and the scores of the Eysenck Personality Questionnaire extraversion subscale. The mean GMV of the left ACC was negatively correlated with the WCST number of errors and persistent error response. Negative correlation was found between the causal effect from the left ACC to the right middle temporal gyrus and the scores of WCST number of categories achieved. Conclusions: Our findings show the partial effects of structural alterations on the cortico-limbic-cerebellar circuit in first-episode, drug-naive patients with SD. Correlations are observed between anatomical alterations or causal effects and clinical variables in patients with SD, and bear clinical significance. The present study emphasizes the importance of the cortico-limbic-cerebellar circuit in the neurobiology of SD. PMID:29755373

Altered morphology of the nucleus accumbens in persistent developmental stuttering.

PubMed

Neef, Nicole E; Bütfering, Christoph; Auer, Tibor; Metzger, F Luise; Euler, Harald A; Frahm, Jens; Paulus, Walter; Sommer, Martin

2018-03-01

Neuroimaging studies in persistent developmental stuttering repeatedly report altered basal ganglia functions. Together with thalamus and cerebellum, these structures mediate sensorimotor functions and thus represent a plausible link between stuttering and neuroanatomy. However, stuttering is a complex, multifactorial disorder. Besides sensorimotor functions, emotional and social-motivational factors constitute major aspects of the disorder. Here, we investigated cortical and subcortical gray matter regions to study whether persistent developmental stuttering is also linked to alterations of limbic structures. The study included 33 right-handed participants who stutter and 34 right-handed control participants matched for sex, age, and education. Structural images were acquired using magnetic resonance imaging to estimate volumetric characteristics of the nucleus accumbens, hippocampus, amygdala, pallidum, putamen, caudate nucleus, and thalamus. Volumetric comparisons and vertex-based shape comparisons revealed structural differences. The right nucleus accumbens was larger in participants who stutter compared to controls. Recent theories of basal ganglia functions suggest that the nucleus accumbens is a motivation-to-movement interface. A speaker intends to reach communicative goals, but stuttering can derail these efforts. It is therefore highly plausible to find alterations in the motivation-to-movement interface in stuttering. While behavioral studies of stuttering sought to find links between the limbic and sensorimotor system, we provide the first neuroimaging evidence of alterations in the limbic system. Thus, our findings might initialize a unified neurobiological framework of persistent developmental stuttering that integrates sensorimotor and social-motivational neuroanatomical circuitries. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective Limbic Blood–Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies

PubMed Central

Tröscher, Anna R.; Klang, Andrea; French, Maria; Quemada-Garrido, Lucía; Kneissl, Sibylle Maria; Bien, Christian G.; Pákozdy, Ákos; Bauer, Jan

2017-01-01

Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1) is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC) complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO), is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood–brain barrier (BBB) leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system. PMID:29093718

Selective Limbic Blood-Brain Barrier Breakdown in a Feline Model of Limbic Encephalitis with LGI1 Antibodies.

PubMed

Tröscher, Anna R; Klang, Andrea; French, Maria; Quemada-Garrido, Lucía; Kneissl, Sibylle Maria; Bien, Christian G; Pákozdy, Ákos; Bauer, Jan

2017-01-01

Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1) is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC) complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO), is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood-brain barrier (BBB) leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system.

The role of the medial temporal limbic system in processing emotions in voice and music.

PubMed

Frühholz, Sascha; Trost, Wiebke; Grandjean, Didier

2014-12-01

Subcortical brain structures of the limbic system, such as the amygdala, are thought to decode the emotional value of sensory information. Recent neuroimaging studies, as well as lesion studies in patients, have shown that the amygdala is sensitive to emotions in voice and music. Similarly, the hippocampus, another part of the temporal limbic system (TLS), is responsive to vocal and musical emotions, but its specific roles in emotional processing from music and especially from voices have been largely neglected. Here we review recent research on vocal and musical emotions, and outline commonalities and differences in the neural processing of emotions in the TLS in terms of emotional valence, emotional intensity and arousal, as well as in terms of acoustic and structural features of voices and music. We summarize the findings in a neural framework including several subcortical and cortical functional pathways between the auditory system and the TLS. This framework proposes that some vocal expressions might already receive a fast emotional evaluation via a subcortical pathway to the amygdala, whereas cortical pathways to the TLS are thought to be equally used for vocal and musical emotions. While the amygdala might be specifically involved in a coarse decoding of the emotional value of voices and music, the hippocampus might process more complex vocal and musical emotions, and might have an important role especially for the decoding of musical emotions by providing memory-based and contextual associations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lost for emotion words: What motor and limbic brain activity reveals about autism and semantic theory

PubMed Central

Moseley, Rachel L.; Shtyrov, Yury; Mohr, Bettina; Lombardo, Michael V.; Baron-Cohen, Simon; Pulvermüller, Friedemann

2015-01-01

Autism spectrum conditions (ASC) are characterised by deficits in understanding and expressing emotions and are frequently accompanied by alexithymia, a difficulty in understanding and expressing emotion words. Words are differentially represented in the brain according to their semantic category and these difficulties in ASC predict reduced activation to emotion-related words in limbic structures crucial for affective processing. Semantic theories view ‘emotion actions’ as critical for learning the semantic relationship between a word and the emotion it describes, such that emotion words typically activate the cortical motor systems involved in expressing emotion actions such as facial expressions. As ASC are also characterised by motor deficits and atypical brain structure and function in these regions, motor structures would also be expected to show reduced activation during emotion-semantic processing. Here we used event-related fMRI to compare passive processing of emotion words in comparison to abstract verbs and animal names in typically-developing controls and individuals with ASC. Relatively reduced brain activation in ASC for emotion words, but not matched control words, was found in motor areas and cingulate cortex specifically. The degree of activation evoked by emotion words in the motor system was also associated with the extent of autistic traits as revealed by the Autism Spectrum Quotient. We suggest that hypoactivation of motor and limbic regions for emotion word processing may underlie difficulties in processing emotional language in ASC. The role that sensorimotor systems and their connections might play in the affective and social-communication difficulties in ASC is discussed. PMID:25278250

Hyporesponsive Reward Anticipation in the Basal Ganglia following Severe Institutional Deprivation Early in Life

ERIC Educational Resources Information Center

Mehta, Mitul A.; Gore-Langton, Emma; Golembo, Nicole; Colvert, Emma; Williams, Steven C. R.; Sonuga-Barke, Edmund

2010-01-01

Severe deprivation in the first few years of life is associated with multiple difficulties in cognition and behavior. However, the brain basis for these difficulties is poorly understood. Structural and functional neuroimaging studies have implicated limbic system structures as dysfunctional, and one functional imaging study in a heterogeneous…

A revised limbic system model for memory, emotion and behaviour.

PubMed

Catani, Marco; Dell'acqua, Flavio; Thiebaut de Schotten, Michel

2013-09-01

Emotion, memories and behaviour emerge from the coordinated activities of regions connected by the limbic system. Here, we propose an update of the limbic model based on the seminal work of Papez, Yakovlev and MacLean. In the revised model we identify three distinct but partially overlapping networks: (i) the Hippocampal-diencephalic and parahippocampal-retrosplenial network dedicated to memory and spatial orientation; (ii) The temporo-amygdala-orbitofrontal network for the integration of visceral sensation and emotion with semantic memory and behaviour; (iii) the default-mode network involved in autobiographical memories and introspective self-directed thinking. The three networks share cortical nodes that are emerging as principal hubs in connectomic analysis. This revised network model of the limbic system reconciles recent functional imaging findings with anatomical accounts of clinical disorders commonly associated with limbic pathology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Frontal glutamate and reward processing in adolescence and adulthood.

PubMed

Gleich, Tobias; Lorenz, Robert C; Pöhland, Lydia; Raufelder, Diana; Deserno, Lorenz; Beck, Anne; Heinz, Andreas; Kühn, Simone; Gallinat, Jürgen

2015-11-01

The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults. To investigate differences in network interactions, the brain reward system activity (slot machine task) together with frontal glutamate concentration (anterior cingulate cortex, ACC) was measured in 28 adolescents and 26 adults employing functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. An inverse coupling of glutamate concentrations in the ACC and activation of the ventral striatum was observed in adolescents. Further, amygdala response in adolescents was negatively correlated with the personality trait impulsivity. For adults, no significant associations of network components or correlations with impulsivity were found. The inverse association between frontal glutamate concentration and striatal activation in adolescents is in line with the triadic model of motivated behavior stressing the important role of frontal top-down inhibition on limbic structures. Our data identified glutamate as the mediating neurotransmitter of this inhibitory process and demonstrates the relevance of glutamate on the reward system and related behavioral traits like impulsivity. This fronto-limbic coupling may represent a vulnerability factor for psychiatric disorders starting in adolescence but not in adulthood.

Kisspeptin modulates sexual and emotional brain processing in humans.

PubMed

Comninos, Alexander N; Wall, Matthew B; Demetriou, Lysia; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M; Jayasena, Channa N; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Lundanes, Elsa; Wilson, Steven Ray; Brown, Rachel C; Thomas, Sarah A; Bloom, Stephen R; Dhillo, Waljit S

2017-02-01

Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

Evidence for a cerebral cortical thickness network anti-correlated with amygdalar volume in healthy youths: implications for the neural substrates of emotion regulation.

PubMed

Albaugh, Matthew D; Ducharme, Simon; Collins, D Louis; Botteron, Kelly N; Althoff, Robert R; Evans, Alan C; Karama, Sherif; Hudziak, James J

2013-05-01

Recent functional connectivity studies have demonstrated that, in resting humans, activity in a dorsally-situated neocortical network is inversely associated with activity in the amygdalae. Similarly, in human neuroimaging studies, aspects of emotion regulation have been associated with increased activity in dorsolateral, dorsomedial, orbital and ventromedial prefrontal regions, as well as concomitant decreases in amygdalar activity. These findings indicate the presence of two countervailing systems in the human brain that are reciprocally related: a dorsally-situated cognitive control network, and a ventrally-situated limbic network. We investigated the extent to which this functional reciprocity between limbic and dorsal neocortical regions is recapitulated from a purely structural standpoint. Specifically, we hypothesized that amygdalar volume would be related to cerebral cortical thickness in cortical regions implicated in aspects of emotion regulation. In 297 typically developing youths (162 females, 135 males; 572 MRIs), the relationship between cortical thickness and amygdalar volume was characterized. Amygdalar volume was found to be inversely associated with thickness in bilateral dorsolateral and dorsomedial prefrontal, inferior parietal, as well as bilateral orbital and ventromedial prefrontal cortices. Our findings are in line with previous work demonstrating that a predominantly dorsally-centered neocortical network is reciprocally related to core limbic structures such as the amygdalae. Future research may benefit from investigating the extent to which such cortical-limbic morphometric relations are qualified by the presence of mood and anxiety psychopathology. Copyright © 2012 Elsevier Inc. All rights reserved.

Case report: Improvement in dissociative symptoms with mixed amphetamine salts.

PubMed

Scarella, Timothy M; Franzen, Jamie R

2017-01-01

Symptoms of dissociation, including dissociative amnesia, depersonalization, and derealization, commonly develop in individuals subject to chronic and repeated trauma during development. This includes the trauma of environmental inability to facilitate development of adequate cognitive strategies for coping with strong negative emotions. Dissociation likely involves dysregulated balance of prefrontal inhibition of limbic structures and inadequate regulation of attentional bias by both prefrontal and limbic systems. There is currently no established psychopharmacologic treatment for dissociative symptoms. Here the case of a woman with severe dissociative symptoms that were markedly improved with the administration of mixed amphetamine salts is discussed. Potential neurobiologic mechanisms for dissociative symptom improvement with psychostimulants are discussed.

Mirror trends of plasticity and stability indicators in primate prefrontal cortex.

PubMed

García-Cabezas, Miguel Á; Joyce, Mary Kate P; John, Yohan J; Zikopoulos, Basilis; Barbas, Helen

2017-10-01

Research on plasticity markers in the cerebral cortex has largely focused on their timing of expression and role in shaping circuits during critical and normal periods. By contrast, little attention has been focused on the spatial dimension of plasticity-stability across cortical areas. The rationale for this analysis is based on the systematic variation in cortical structure that parallels functional specialization and raises the possibility of varying levels of plasticity. Here, we investigated in adult rhesus monkeys the expression of markers related to synaptic plasticity or stability in prefrontal limbic and eulaminate areas that vary in laminar structure. Our findings revealed that limbic areas are impoverished in three markers of stability: intracortical myelin, the lectin Wisteria floribunda agglutinin, which labels perineuronal nets, and parvalbumin, which is expressed in a class of strong inhibitory neurons. By contrast, prefrontal limbic areas were enriched in the enzyme calcium/calmodulin-dependent protein kinase II (CaMKII), known to enhance plasticity. Eulaminate areas have more elaborate laminar architecture than limbic areas and showed the opposite trend: they were enriched in markers of stability and had lower expression of the plasticity-related marker CaMKII. The expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, was also higher in limbic areas, suggesting that cellular stress correlates with the rate of circuit reshaping. Elevated markers of plasticity may endow limbic areas with flexibility necessary for learning and memory within an affective context, but may also render them vulnerable to abnormal structural changes, as seen in neurologic and psychiatric diseases. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Kisspeptin modulates sexual and emotional brain processing in humans

PubMed Central

Comninos, Alexander N.; Wall, Matthew B.; Demetriou, Lysia; Shah, Amar J.; Clarke, Sophie A.; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K.; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M.; Jayasena, Channa N.; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A.; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Wilson, Steven Ray; Brown, Rachel C.; Thomas, Sarah A.; Bloom, Stephen R.; Dhillo, Waljit S.

2017-01-01

BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. METHODS. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. RESULTS. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin’s enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. CONCLUSIONS. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. FUNDING. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC). PMID:28112678

Amygdala hypersensitivity in response to emotional faces in Tourette's patients.

PubMed

Neuner, Irene; Kellermann, Thilo; Stöcker, Tony; Kircher, Tilo; Habel, Ute; Shah, Jon N; Schneider, Frank

2010-10-01

Tourette's syndrome is characterised by motor and vocal tics as well as a high level of impulsivity and emotional dysregulation. Neuroimaging studies point to structural changes of the basal ganglia, prefrontal cortex and parts of the limbic system. However, there is no link between behavioural symptoms and the structural changes in the amygdala. One aspect of daily social interaction is the perception of emotional facial expressions, closely linked to amgydala function. We therefore investigated via fMRI the implicit discrimination of six emotional facial expressions in 19 adult Tourette's patients. In comparison to healthy control group, Tourette's patients showed significantly higher amygdala activation, especially pronounced for fearful, angry and neutral expressions. The BOLD-activity of the left amygdala correlated negatively with the personality trait extraversion. We will discuss these findings as a result of either deficient frontal inhibition due to structural changes or a desynchronization in the interaction of the cortico-striato-thalamo-cortical network within structures of the limbic system. Our data show an altered pattern of implicit emotion discrimination and emphasize the need to consider motor and non-motor symptoms in Tourette's syndrome in the choice of both behavioural and pharmacological treatment.

Neuropsychological and FDG-PET profiles in VGKC autoimmune limbic encephalitis.

PubMed

Dodich, Alessandra; Cerami, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Alongi, Pierpaolo; Crespi, Chiara; Canessa, Nicola; Andreetta, Francesca; Falini, Andrea; Cappa, Stefano F; Perani, Daniela

2016-10-01

Limbic encephalitis (LE) is characterized by an acute or subacute onset with memory impairments, confusional state, behavioral disorders, variably associated with seizures and dystonic movements. It is due to inflammatory processes that selectively affect the medial temporal lobe structures. Voltage-gate potassium channel (VGKC) autoantibodies are frequently observed. In this study, we assessed at the individual level FDG-PET brain metabolic dysfunctions and neuropsychological profiles in three autoimmune LE cases seropositive for neuronal VGKC-complex autoantibodies. LGI1 and CASPR2 potassium channel complex autoantibody subtyping was performed. Cognitive abilities were evaluated with an in-depth neuropsychological battery focused on episodic memory and affective recognition/processing skills. FDG-PET data were analyzed at single-subject level according to a standardized and validated voxel-based Statistical Parametric Mapping (SPM) method. Patients showed severe episodic memory and fear recognition deficits at the neuropsychological assessment. No disorder of mentalizing processing was present. Variable patterns of increases and decreases of brain glucose metabolism emerged in the limbic structures, highlighting the pathology-driven selective vulnerability of this system. Additional involvement of cortical and subcortical regions, particularly in the sensorimotor system and basal ganglia, was found. Episodic memory and fear recognition deficits characterize the cognitive profile of LE. Commonalities and differences may occur in the brain metabolic patterns. Single-subject voxel-based analysis of FDG-PET imaging could be useful in the early detection of the metabolic correlates of cognitive and non-cognitive deficits characterizing LE condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Limbic encephalitis and antibodies to Ma2: a paraneoplastic presentation of breast cancer

PubMed Central

Sutton, I.; Winer, J.; Rowlands, D.; Dalmau, J.

2000-01-01

A patient with atypical medullary breast cancer is described who presented with symptoms of limbic encephalitis. The patient's serum and CSF contained antibodies that reacted with the nervous system and the tumour. These antibodies recognised Ma2, a neuronal protein related to paraneoplastic limbic and brainstem encephalitis in men with testicular tumours. This report highlights the importance of testing for paraneoplastic antineuronal antibodies in cases of unexplained limbic encephalitis and suggests screening for breast cancer in women with antibodies predominantly directed to Ma2.

 PMID:10896708

Limbic encephalitis and antibodies to Ma2: a paraneoplastic presentation of breast cancer.

PubMed

Sutton, I; Winer, J; Rowlands, D; Dalmau, J

2000-08-01

A patient with atypical medullary breast cancer is described who presented with symptoms of limbic encephalitis. The patient's serum and CSF contained antibodies that reacted with the nervous system and the tumour. These antibodies recognised Ma2, a neuronal protein related to paraneoplastic limbic and brainstem encephalitis in men with testicular tumours. This report highlights the importance of testing for paraneoplastic antineuronal antibodies in cases of unexplained limbic encephalitis and suggests screening for breast cancer in women with antibodies predominantly directed to Ma2.

Clinically Anxious Individuals Show Disrupted Feedback between Inferior Frontal Gyrus and Prefrontal-Limbic Control Circuit.

PubMed

Cha, Jiook; DeDora, Daniel; Nedic, Sanja; Ide, Jaime; Greenberg, Tsafrir; Hajcak, Greg; Mujica-Parodi, Lilianne Rivka

2016-04-27

Clinical anxiety is associated with generalization of conditioned fear, in which innocuous stimuli elicit alarm. Using Pavlovian fear conditioning (electric shock), we quantify generalization as the degree to which subjects' neurobiological responses track perceptual similarity gradients to a conditioned stimulus. Previous studies show that the ventromedial prefrontal cortex (vmPFC) inversely and ventral tegmental area directly track the gradient of perceptual similarity to the conditioned stimulus in healthy individuals, whereas clinically anxious individuals fail to discriminate. Here, we extend this work by identifying specific functional roles within the prefrontal-limbic circuit. We analyzed fMRI time-series acquired from 57 human subjects during a fear generalization task using entropic measures of circuit-wide regulation and feedback (power spectrum scale invariance/autocorrelation), in combination with structural (diffusion MRI-probabilistic tractography) and functional (stochastic dynamic causal modeling) measures of prefrontal-limbic connectivity within the circuit. Group comparison and correlations with anxiety severity across 57 subjects revealed dysregulatory dynamic signatures within the inferior frontal gyrus (IFG), which our prior work has linked to impaired feedback within the circuit. Bayesian model selection then identified a fully connected prefrontal-limbic model comprising the IFG, vmPFC, and amygdala. Dysregulatory IFG dynamics were associated with weaker reciprocal excitatory connectivity between the IFG and the vmPFC. The vmPFC exhibited inhibitory influence on the amygdala. Our current results, combined with our previous work across a threat-perception spectrum of 137 subjects and a meta-analysis of 366 fMRI studies, dissociate distinct roles for three prefrontal-limbic regions, wherein the IFG provides evaluation of stimulus meaning, which then informs the vmPFC in inhibiting the amygdala. Affective neuroscience has generally treated prefrontal regions (orbitofrontal cortex, dorsolateral prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex) equivalently as inhibitory components of the prefrontal-limbic system. Yet research across the anxiety spectrum suggests that the inferior frontal gyrus may have a more complex role in emotion regulation, as this region shows abnormal function in disorders of both hyperarousal and hypoarousal. Using entropic measures of circuit-wide regulation and feedback, in combination with measures of structural and functional connectivity, we dissociate distinct roles for three prefrontal-limbic regions, wherein the inferior frontal gyrus provides evaluation of stimulus meaning, which then informs the ventromedial prefrontal cortex in inhibiting the amygdala. This reconfiguration coheres with studies of conceptual disambiguation also implicating the inferior frontal gyrus. Copyright © 2016 the authors 0270-6474/16/364708-11$15.00/0.

Sex differences in structural brain asymmetry predict overt aggression in early adolescents.

PubMed

Visser, Troy A W; Ohan, Jeneva L; Whittle, Sarah; Yücel, Murat; Simmons, Julian G; Allen, Nicholas B

2014-04-01

The devastating social, emotional and economic consequences of human aggression are laid bare nightly on newscasts around the world. Aggression is principally mediated by neural circuitry comprising multiple areas of the prefrontal cortex and limbic system, including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), amygdala and hippocampus. A striking characteristic of these regions is their structural asymmetry about the midline (i.e. left vs right hemisphere). Variations in these asymmetries have been linked to clinical disorders characterized by aggression and the rate of aggressive behavior in psychiatric patients. Here, we show for the first time that structural asymmetries in prefrontal cortical areas are also linked to aggression in a normal population of early adolescents. Our findings indicate a relationship between parent reports of aggressive behavior in adolescents and structural asymmetries in the limbic and paralimbic ACC and OFC, and moreover, that this relationship varies by sex. Furthermore, while there was no relationship between aggression and structural asymmetries in the amygdala or hippocampus, hippocampal volumes did predict aggression in females. Taken together, the results suggest that structural asymmetries in the prefrontal cortex may influence human aggression, and that the anatomical basis of aggression varies substantially by sex.

Methylphenidate administration determines enduring changes in neuroglial network in rats.

PubMed

Cavaliere, Carlo; Cirillo, Giovanni; Bianco, Maria Rosaria; Adriani, Walter; De Simone, Antonietta; Leo, Damiana; Perrone-Capano, Carla; Papa, Michele

2012-01-01

Repeated exposure to psychostimulant drugs induces complex molecular and structural modifications in discrete brain regions of the meso-cortico-limbic system. This structural remodeling is thought to underlie neurobehavioral adaptive responses. Administration to adolescent rats of methylphenidate (MPH), commonly used in attention deficit and hyperactivity disorder (ADHD), triggers alterations of reward-based behavior paralleled by persistent and plastic synaptic changes of neuronal and glial markers within key areas of the reward circuits. By immunohistochemistry, we observe a marked increase of glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) expression and a down-regulation of glial glutamate transporter GLAST in dorso-lateral and ventro-medial striatum. Using electron microscopy, we find in the prefrontal cortex a significant reduction of the synaptic active zone length, paralleled by an increase of dendritic spines. We demonstrate that in limbic areas the MPH-induced reactive astrocytosis affects the glial glutamatergic uptake system that in turn could determine glutamate receptor sensitization. These processes could be sustained by NO production and synaptic rearrangement and contribute to MPH neuroglial induced rewiring. Copyright © 2011. Published by Elsevier B.V.

Identification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala

PubMed Central

Hirata, Tsutomu; Li, Peijun; Lanuza, Guillermo M.; Cocas, Laura A.; Huntsman, Molly M.; Corbin, Joshua G.

2009-01-01

Development of the amygdala, a central structure of the limbic system, remains poorly understood. Using mouse as a model, our studies reveal that two spatially distinct and early specified telencephalic progenitor pools marked by the homeodomain transcription factor Dbx1 are major sources of neuronal cell diversity in the mature amygdala. We find that Dbx1+ cells of the ventral pallium (VP) generate excitatory neurons of the basolateral complex and cortical amygdala nuclei. Moreover, Dbx1-derived cells comprise a novel migratory stream that emanates from the preoptic area (POA), a ventral telencephalic domain adjacent to the diencephalic border. The Dbx1+ POA-derived population migrates specifically to the amygdala, and as defined by both immunochemical and electrophysiological criteria, generates a unique subclass of inhibitory neurons in the medial amygdala nucleus. Thus, this POA-derived population represents a novel progenitor pool dedicated to the limbic system. PMID:19136974

Identification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala.

PubMed

Hirata, Tsutomu; Li, Peijun; Lanuza, Guillermo M; Cocas, Laura A; Huntsman, Molly M; Corbin, Joshua G

2009-02-01

The development of the amygdala, a central structure of the limbic system, remains poorly understood. We found that two spatially distinct and early-specified telencephalic progenitor pools marked by the homeodomain transcription factor Dbx1 are major sources of neuronal cell diversity in the mature mouse amygdala. We found that Dbx1-positive cells of the ventral pallium generate the excitatory neurons of the basolateral complex and cortical amygdala nuclei. Moreover, Dbx1-derived cells comprise a previously unknown migratory stream that emanates from the preoptic area (POA), a ventral telencephalic domain adjacent to the diencephalic border. The Dbx1-positive, POA-derived population migrated specifically to the amygdala and, as defined by both immunochemical and electrophysiological criteria, generated a unique subclass of inhibitory neurons in the medial amygdala nucleus. Thus, this POA-derived population represents a previously unknown progenitor pool dedicated to the limbic system.

TRIMETHYLTIN, A SELECTIVE LIMBIC SYSTEM NEUROTOXICANT, IMPAIRS RADIAL-ARM MAZE PERFORMANCE

EPA Science Inventory

Rats were trained for fifteen sessions in an automated eight arm radial maze prior to treatment with 6 mg/kg trimethyltin chloride. This compound is a neurotoxicant which primarily damages the limbic system, in particular pyramidal cells in the CA3 region of the hippocampus. Foll...

Neurocircuitry of Mood Disorders

PubMed Central

Price, Joseph L; Drevets, Wayne C

2010-01-01

This review begins with a brief historical overview of attempts in the first half of the 20th century to discern brain systems that underlie emotion and emotional behavior. These early studies identified the amygdala, hippocampus, and other parts of what was termed the ‘limbic' system as central parts of the emotional brain. Detailed connectional data on this system began to be obtained in the 1970s and 1980s, as more effective neuroanatomical techniques based on axonal transport became available. In the last 15 years these methods have been applied extensively to the limbic system and prefrontal cortex of monkeys, and much more specific circuits have been defined. In particular, a system has been described that links the medial prefrontal cortex and a few related cortical areas to the amygdala, the ventral striatum and pallidum, the medial thalamus, the hypothalamus, and the periaqueductal gray and other parts of the brainstem. A large body of human data from functional and structural imaging, as well as analysis of lesions and histological material indicates that this system is centrally involved in mood disorders. PMID:19693001

Overwhelming remembrance of things past: Proust portrays limbic kindling by external stimulus--literary genius can presage neurobiological patterns of puzzling behavior.

PubMed

Pontius, A A

1993-10-01

Proust detailed inexplicable behavior long before the neurobiologists Goddard and McIntyre in 1972 demonstrated that intermittent repetition of harmless stimuli can cause "kindling" of a seizure (with or without motor convulsions). Such brief seizures can occur especially in the evolutionarily old limbic system which mediates basic drives, their concomitant emotions, and certain aspects of memory. It appears that in humans the influence of specific external stimuli that revive the memory of repeated past experiences may "kindle" a transient episode of limbic overactivation. Thereupon the normal balance between the limbic and frontal lobe systems is disturbed (for a few minutes) as are normal human decision making and control of action. Linked with such a transient frontolimbic imbalance is out-of-character behavior, psychosis (hallucinations or delusions), autonomic activation, and severe distortion of affect and of action, culminating in extreme cases in a "Limbic Psychotic Trigger Reaction," as proposed by Pontius in 1981, in motiveless homicidal acts with mostly preserved consciousness and memory for the acts.

Effects of normal aging and Alzheimer's disease on emotional memory.

PubMed

Kensinger, Elizabeth A; Brierley, Barbara; Medford, Nick; Growdon, John H; Corkin, Suzanne

2002-06-01

Recall is typically better for emotional than for neutral stimuli. This enhancement is believed to rely on limbic regions. Memory is also better for neutral stimuli embedded in an emotional context. The neural substrate supporting this effect has not been thoroughly investigated but may include frontal lobe, as well as limbic circuits. Alzheimer's disease (AD) results in atrophy of limbic structures, whereas normal aging relatively spares limbic regions but affects prefrontal areas. The authors hypothesized that AD would reduce all enhancement effects, whereas aging would disproportionately affect enhancement based on emotional context. The results confirmed the authors' hypotheses: Young and older adults, but not AD patients, showed better memory for emotional versus neutral pictures and words. Older adults and AD patients showed no benefit from emotional context, whereas young adults remembered more items embedded in an emotional versus neutral context.

Hypothermia in VGKC antibody-associated limbic encephalitis.

PubMed

Jacob, S; Irani, S R; Rajabally, Y A; Grubneac, A; Walters, R J; Yazaki, M; Clover, L; Vincent, A

2008-02-01

Voltage-gated potassium channel antibody (VGKC-Ab)-associated limbic encephalitis (LE) is a recently described syndrome that broadens the spectrum of immunotherapy-responsive central nervous system disorders. Limbic encephalitis is typically characterised by a sub-acute onset of disorientation, amnesia and seizures, but the clinical spectrum is not yet fully defined and the syndrome could be under-diagnosed. We here describe the clinical profile of four patients with VGKC-Ab-associated LE who had intermittent, episodic hypothermia. One of the patients also described a prodrome of severe neuropathic pain preceding the development of limbic symptoms. Both of these novel symptoms responded well to immunosuppressive therapy, with concurrent amelioration of amnesia/seizures.

The Role of Protein Synthesis and Monoamines in the Production of Long-Term Potentiation in the Rat Hippocampal Slice

DTIC Science & Technology

1985-04-01

ability may be a first step in understanding how learning takes place. The hippocampus is a cortical structure which has fascinated researchers for...some time. It is a discrete and very organized part of the limbic system, and is one of the earliest cortical structures to evolve. One fact stands...and Mcilwain, 1966; Yamamoto, 1972]. Since the hippocampus is a lamellar structure , thin (300-500~) slices cut perpendicular to the axis of the

Negative functional coupling between the right fronto-parietal and limbic resting state networks predicts increased self-control and later substance use onset in adolescence.

PubMed

Lee, Tae-Ho; Telzer, Eva H

2016-08-01

Recent developmental brain imaging studies have demonstrated that negatively coupled prefrontal-limbic circuitry implicates the maturation of brain development in adolescents. Using resting-state functional magnetic resonance imaging (rs-fMRI) and independent component analysis (ICA), the present study examined functional network coupling between prefrontal and limbic systems and links to self-control and substance use onset in adolescents. Results suggest that negative network coupling (anti-correlated temporal dynamics) between the right fronto-parietal and limbic resting state networks is associated with greater self-control and later substance use onset in adolescents. These findings increase our understanding of the developmental importance of prefrontal-limbic circuitry for adolescent substance use at the resting-state network level. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A neurophysiologic model for aggressive behavior in the cat.

PubMed

Andy, O J; Giurintano, L P; Giurintano, S L

1978-01-01

A neurophysiologic model for aggressive behavior in the cat is proposed. Stimulus-bound and seizure-bound aggression was evaluated in relation to limbic and basal ganglia induced seizures (after-discharges). Electrically induced limbic and basal ganglia after-discharges were used because they are known to implicate septohypothalamic sites from which aggression can be elicited by direct stimulation. The occurrence of behavioral aggression is correlated with the discharge characteristics of a single discharging system and with two interacting discharging systems. Aggression is composed of autonomic and somato-motor components which poses relatively low and high thresholds, respectively, for their activation. Aggression occurring during a combined septum and amygdala discharge was more intense and prolonged than with a septum discharge alone. Participation of a slow frequency discharging basal ganglia system activated seizure-bound aggression in an otherwise nonaggressive limbic seizure. The limbic and basal ganglia stimulations and after-discharges lowered the excitability threshold of the aggression system and made it more vulnerable to being activated by external stimuli, such as visual and auditory stimuli. These observations are reminiscent of patients with aggressive behavior associated with psychomotor seizures.

Molecular and Cellular Sex Differences at the Intersection of Stress and Arousal

PubMed Central

Valentino, Rita J.; Reyes, Beverly; Van Bockstaele, Elisabeth; Bangasser, Debra

2011-01-01

Elucidating the mechanisms underlying sex biases in the prevalence and severity of diseases can advance our understanding of their pathophysiological basis and serve as a guide for developing treatments. A well-established sex difference in psychiatry is the higher incidence of mood and anxiety disorders in females. These disorders share stress as a potential etiological contributor and hyperarousal as a core symptom, suggesting that the distinction between sexes lies at the intersection of stress and arousal systems. This review focuses on the link between the stress axis and the brain norepinephrine arousal system as a key point at which sex differences occur and are translated to differences in the expression of mood disorders. Evidence for a circuit designed to relay emotion-related information via the limbic corticotropin-releasing factor (CRF) system to the locus coeruleus (LC)–norepinephrine arousal system is reviewed. This is followed by recent novel findings of sex differences in CRF receptor signaling and trafficking that would result in an enhanced arousal response and a compromised ability to adapt to chronic stress in females. Finally, we discuss evidence for sex differences in LC dendritic structure that allow for increased receipt and processing of limbic information in females compared to males. Together these complementary sets of data suggest that in females, the LC arousal system is poised to process more limbic information and to respond to some of this information in an enhanced manner compared to males. The clinical and therapeutic considerations arising from this perspective are discussed. PMID:21712048

[Limbic encephalitis with antibodies against intracellular antigens].

PubMed

Morita, Akihiko; Kamei, Satoshi

2010-04-01

Limbic encephalitis is a paraneoplastic syndrome that is often associated with small cell lung cancer (SCLC), breast cancer, testicular tumors, teratoma, Hodgkin's lymphoma and thymoma. The common clinical manifestations of limbic encephalitis are subacute onset, cognitive dysfunction, seizures and psychiatric symptoms. Paraneoplastic neurological disorders are considered to occur because of cytotoxic T cell responses and antibodies against target neuronal proteins that are usually expressed by an underlying tumor. The main intracellular antigens related to limbic encephalitis are Hu, Ma2, and less frequently CV2/CRMP5 and amphiphysin. The anti-Hu antibody, which is involved in cerebellar degeneration and extensive or multifocal encephalomyelitis such as limbic encephalitis is closely associated with a history of smoking and SCLC. The anti-Ma2 antibody is associated with encephalitis of the limbic system, hypothalamus and brain-stem. For this reason, some patients with limbic encephalitis have sleep disorders (including REM sleep abnormalities), severe hypokinesis and gaze palsy in addition to limbic dysfunction. In men aged less than 50 years, anti-Ma2 antibody encephalitis is almost always associated with testicular germ-cell tumors that are occasionally difficult to detect. In older men and women, the most common tumors are non-SCLC and breast cancer. Limbic encephalitis associated with cell-surface antigens (e.g., voltage-gated potassium channels, NMDA receptors) is mediated by antibodies and often improves after a reduction in the antibody titer and after tumor resection. Patients with antibodies against intracellular antigens, except for those with anti-Ma2 antibodies and testicular tumors, are less responsive. Early diagnosis and treatment with immunotherapy, tumor resection or both are important for improving or stabilizing the condition of limbic encephalitis.

Limbic encephalitis following immunotherapy against metastatic malignant melanoma

PubMed Central

Salam, Sharfaraz; Lavin, Timothy; Turan, Ayse

2016-01-01

Novel immunotherapies are increasingly being used to treat malignant melanoma. The use of such agents has been associated with triggering autoimmunity. However, there has been a paucity in reports of limbic encephalitis associated with these immunotherapies. Pembrolizumab, a monoclonal antibody against programmed cell death antigen (PD-1), is currently being trialled in the UK to treat malignant melanoma. We report a unique case of antibody-negative limbic encephalitis presenting 1 year after starting pembrolizumab, in the context of malignant melanoma. The patient presented with progressive cognitive decline. MRI of the brain revealed signal change within the limbic structures. Cerebrospinal fluid studies confirmed evidence of inflammation with raised white cell count and protein. We were able to prevent further progression of symptoms by stopping pembrolizumab and treating the patient instead with steroids. We advocate considering autoimmune neuroinflammation as a differential for neurological disorders presenting in patients receiving PD-1 antagonist treatment and immunotherapy in general. PMID:27009198

Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miletich, R.S.

The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and /sup 3/H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by ..cap alpha..-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period,more » phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S/sub 2/ episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. /sup 3/H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system.« less

Aberrant paralimbic gray matter in criminal psychopathy.

PubMed

Ermer, Elsa; Cope, Lora M; Nyalakanti, Prashanth K; Calhoun, Vince D; Kiehl, Kent A

2012-08-01

Psychopaths impose large costs on society, as they are frequently habitual, violent criminals. The pervasive nature of emotional and behavioral symptoms in psychopathy suggests that several associated brain regions may contribute to the disorder. Studies employing a variety of methods have converged on a set of brain regions in paralimbic cortex and limbic areas that appear to be dysfunctional in psychopathy. The present study further tests this hypothesis by investigating structural abnormalities using voxel-based morphometry in a sample of incarcerated men (N=296). Psychopathy was associated with decreased regional gray matter in several paralimbic and limbic areas, including bilateral parahippocampal, amygdala, and hippocampal regions, bilateral temporal pole, posterior cingulate cortex, and orbitofrontal cortex. The consistent identification of paralimbic cortex and limbic structures in psychopathy across diverse methodologies strengthens the interpretation that these regions are crucial for understanding neural dysfunction in psychopathy. PsycINFO Database Record (c) 2012 APA, all rights reserved.

[Forensic neuropsychology at the challenge of the relationship between cognition and emotion in psychopathy].

PubMed

Alcázar-Córcoles, M A; Verdejo-García, A; Bouso-Saiz, J C

The relationship between frontal lobe damage and criminality is especially complex. The neural substrates of psychopathic behavior seem to involve structural and functional abnormalities in the frontal lobes and the limbic system. AIM. To analyze the repercussions that brain structural and functional abnormalities in psychopathic individuals may have for forensic neuropsychology. Consistent evidence indicate that response inhibition problems in psychopathic subjects are linked to structural or functional damage in the frontal cortex. Furthermore, the prefrontal cortex, along with the amygdala and the hippocampus forms the limbic system, which is an important neural substrate of emotion processing; therefore the psychopath's capacity of affective processing could also be impaired. The theoretical frameworks of the somatic marker and mirror neuron hypotheses, along with the empirical study of executive functions may contribute to explain the inability of the psychopathic subjects to feel empathy, which is one of the main inhibitors of violence and antisocial behavior. The relationship between frontal lobe dysfunction and antisocial behavior arises an important legal issue. In order to consider some type of minor liability in the case of psychopaths it is suggested to gather further research data about the relationship between frontal lobe dysfunction and the ability to inhibit antisocial behavior by making an adequate use of empathy and emotional ties.

Neurochemical background and approaches in the understanding of motion sickness

NASA Technical Reports Server (NTRS)

Kohl, R. L.

1982-01-01

The problems and nature of space motion sickness were defined. The neurochemical and neurophysiological bases of vestibular system function and of the expression of motion sickness wre reviewed. Emphasis was given to the elucidation of the neuropharmacological mechanisms underlying the effects of scopolamine and amphetamine on motion sickness. Characterization of the ascending reticular activating system and the limbic system provided clues to the etiology of the side effects of scopolamine. The interrelationship between central cholinergic pathways and the peripheral (autonomic) expression of motion sickness was described. A correlation between the stress of excessive motion and a variety of hormonal responses to that stress was also detailed. The cholinergic system is involved in the efferent modulation of the vestibular hair cells, as an afferent modulator of the vestibular nuclei, in the activation of cortical and limbic structures, in the expression of motion sickness symptoms and most likely underscores a number of the hormonal changes that occur in stressful motion environments. The role of lecithin in the regulation of the levels of neurotransmitters was characterized as a possible means by which cholinergic neurochemistry can be modulated.

Influence of lesions of the limbic-hypothalamic system on adrenocortical responses to daily repeated heat exposures in rabbits.

PubMed

Seto, K; Kaba, H; Saito, H; Edashige, N; Kawakami, M

1983-07-01

The effects of lesions in the basal medial hypothalamus and limbic structure upon the responses of adrenocorticoids formation in adrenal slices of rabbits to daily repeated heat exposures has been investigated. (1) The adrenocortical responses to heat exposure on the 1st day were decreased by lesions in the periventricular arcuate nucleus (ARC), ventromedial hypothalamus (VMH), stria terminalis (ST) and dorsal fornix (FX). (2) There were no effects of heat exposure on the 10th day upon the adrenocorticoid formation in either the sham-lesioned rabbits or the rabbits with the lesions of ARC, VMH and ST. (3) In rabbits with the FX lesions, the adrenocorticoids formation was significantly increased by heat exposure on the 10th day. (4) These results suggested that the basal medial hypothalamus, amygdala (AMYG)-ST system and dorsal hippocampus (HPC)-FX system participated in the mechanisms of adrenocortical responses to heat exposure on the 1st day, but only the HPC-FX system played some roles in complete disappearance process of adrenocortical responses to heat exposure by repetition of exposures.

[[superscript 3]H]-Flunitrazepam-Labeled Benzodiazepine Binding Sites in the Hippocampal Formation in Autism: A Multiple Concentration Autoradiographic Study

ERIC Educational Resources Information Center

Guptill, Jeffrey T.; Booker, Anne B.; Gibbs, Terrell T.; Kemper, Thomas L.; Bauman, Margaret L.; Blatt, Gene J.

2007-01-01

Increasing evidence indicates that the GABAergic system in cerebellar and limbic structures is affected in autism. We extended our previous study that found reduced [[superscript 3]H] flunitrazepam-labeled benzodiazepine sites in the autistic hippocampus to determine whether this reduction was due to a decrease in binding site number (B [subscript…

Childhood maltreatment moderates the effect of combat exposure on cingulum structural integrity

PubMed Central

BANIHASHEMI, LAYLA; WALLACE, MEREDITH L.; SHEU, LEI K.; LEE, MICHAEL C.; GIANAROS, PETER J.; MACKENZIE, ROBERT P.; INSANA, SALVATORE P.; GERMAIN, ANNE; HERRINGA, RYAN J.

2017-01-01

Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure. PMID:29162178

Molecular and cellular sex differences at the intersection of stress and arousal.

PubMed

Valentino, Rita J; Reyes, Beverly; Van Bockstaele, Elisabeth; Bangasser, Debra

2012-01-01

Elucidating the mechanisms underlying sex biases in the prevalence and severity of diseases can advance our understanding of their pathophysiological basis and serve as a guide for developing treatments. A well-established sex difference in psychiatry is the higher incidence of mood and anxiety disorders in females. These disorders share stress as a potential etiological contributor and hyperarousal as a core symptom, suggesting that the distinction between sexes lies at the intersection of stress and arousal systems. This review focuses on the link between the stress axis and the brain norepinephrine arousal system as a key point at which sex differences occur and are translated to differences in the expression of mood disorders. Evidence for a circuit designed to relay emotion-related information via the limbic corticotropin-releasing factor (CRF) system to the locus coeruleus (LC)-norepinephrine arousal system is reviewed. This is followed by recent novel findings of sex differences in CRF receptor signaling and trafficking that would result in an enhanced arousal response and a compromised ability to adapt to chronic stress in females. Finally, we discuss the evidence for sex differences in LC dendritic structure that allow for an increased receipt and processing of limbic information in females compared to males. Together these complementary sets of data suggest that in females, the LC arousal system is poised to process more limbic information and to respond to some of this information in an enhanced manner compared to males. The clinical and therapeutic considerations arising from this perspective are discussed. This article is part of a Special Issue entitled 'Anxiety and Depression'. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prolonged Febrile Seizures in the Immature Rat Model Enhance Hippocampal Excitability Long Term

PubMed Central

Dube, Celine; Chen, Kang; Eghbal-Ahmadi, Mariam; Brunson, Kristen; Soltesz, Ivan; Baram, Tallie Z.

2011-01-01

Febrile seizures (FSs) constitute the most prevalent seizure type during childhood. Whether prolonged FSs alter limbic excitability, leading to spontaneous seizures (temporal lobe epilepsy) during adulthood, has been controversial. Recent data indicate that, in the immature rat model, prolonged FSs induce transient structural changes of some hippocampal pyramidal neurons and long-term functional changes of hippocampal circuitry. However, whether these neuroanatomical and electrophysiological changes promote hippocampal excitability and lead to epilepsy has remained unknown. By using in vivo and in vitro approaches, we determined that prolonged hyperthermia-induced seizures in immature rats caused long-term enhanced susceptibility to limbic convulsants that lasted to adulthood. Thus, extensive hippocampal electroencephalographic and behavioral monitoring failed to demonstrate spontaneous seizures in adult rats that had experienced hyperthermic seizures during infancy. However, 100% of animals developed hippocampal seizures after systemic administration of a low dose of kainate, and most progressed to status epilepticus. Conversely, a minority of normothermic and hyperthermic controls had (brief) seizures, none developing status epilepticus. In vitro, spontaneous epileptiform discharges were not observed in hippocampal-entorhinal cortex slices derived from either control or experimental groups. However, Schaeffer collateral stimulation induced prolonged, self-sustaining, status epilepticus-like discharges exclusively in slices from experimental rats. These data indicate that hyperthermic seizures in the immature rat model of FSs do not cause spontaneous limbic seizures during adulthood. However, they reduce thresholds to chemical convulsants in vivo and electrical stimulation in vitro, indicating persistent enhancement of limbic excitability that may facilitate the development of epilepsy. PMID:10716253

Graph Theoretical Analysis of BOLD Functional Connectivity during Human Sleep without EEG Monitoring.

PubMed

Lv, Jun; Liu, Dongdong; Ma, Jing; Wang, Xiaoying; Zhang, Jue

2015-01-01

Functional brain networks of human have been revealed to have small-world properties by both analyzing electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) time series. In our study, by using graph theoretical analysis, we attempted to investigate the changes of paralimbic-limbic cortex between wake and sleep states. Ten healthy young people were recruited to our experiment. Data from 2 subjects were excluded for the reason that they had not fallen asleep during the experiment. For each subject, blood oxygen level dependency (BOLD) images were acquired to analyze brain network, and peripheral pulse signals were obtained continuously to identify if the subject was in sleep periods. Results of fMRI showed that brain networks exhibited stronger small-world characteristics during sleep state as compared to wake state, which was in consistent with previous studies using EEG synchronization. Moreover, we observed that compared with wake state, paralimbic-limbic cortex had less connectivity with neocortical system and centrencephalic structure in sleep. In conclusion, this is the first study, to our knowledge, has observed that small-world properties of brain functional networks altered when human sleeps without EEG synchronization. Moreover, we speculate that paralimbic-limbic cortex organization owns an efficient defense mechanism responsible for suppressing the external environment interference when humans sleep, which is consistent with the hypothesis that the paralimbic-limbic cortex may be functionally disconnected from brain regions which directly mediate their interactions with the external environment. Our findings also provide a reasonable explanation why stable sleep exhibits homeostasis which is far less susceptible to outside world.

Neuropharmacological Specificity of Brain Structures Involved in Soman-Induced Seizures

DTIC Science & Technology

2012-01-01

Bernabé Burckhart M-F, Lallement G. Efficacy of the ketamine-atropine combination in the delayed treatment of soman- induced status epilepticus ...The functional anatomy of limbic status epilepticus in the rat. I. Patterns of 14C-2-deoxyglucose uptake and fos immunochemistry. Journal of...Neuroscience 1993a;13(11):4787–801. White LE, Price JL. The functional anatomy of limbic status epilepticus in the rat. II. The effects of focal deactivation

Bilateral limbic system destruction in man

PubMed Central

Feinstein, Justin S.; Rudrauf, David; Khalsa, Sahib S.; Cassell, Martin D.; Bruss, Joel; Grabowski, Thomas J.; Tranel, Daniel

2010-01-01

We report here a case study of a rare neurological patient with bilateral brain damage encompassing a substantial portion of the so-called “limbic system.” The patient, Roger, has been studied in our laboratory for over 14 years and the current article presents his complete neuroanatomical and neuropsychological profiles. The brain damage occurred in 1980 following an episode of herpes simplex encephalitis. The amount of destroyed neural tissue is extensive and includes bilateral damage to core limbic and paralimbic regions, including the hippocampus, amygdala, parahippocampal gyrus, temporal poles, orbitofrontal cortex, basal forebrain, anterior cingulate cortex, and insular cortex. The right hemisphere is more extensively affected than the left, although the lesions are largely bilateral. Despite the magnitude of his brain damage, Roger has a normal IQ, average to above average attention, working memory, and executive functioning skills, and very good speech and language abilities. In fact, his only obvious presenting deficits are a dense global amnesia and a severe anosmia and ageusia. Roger's case presents a rare opportunity to advance our understanding of the critical functions underlying the human limbic system, and the neuropsychological and neuroanatomical data presented here provide a critical foundation for such investigations. PMID:19763994

[Comparative study of effects of cortical nucleus of amygdala and pyriform cortex on activity of bulbar respiratory neurons in cats].

PubMed

Nersesian, L B; Eganova, V S; Pogosian, N L; Avetisian, I N

2011-01-01

Comparative microelectrophysiological study of character and peculiarities of effects of the cortical nucleus of amygdala and of the periamygdalar area of pyriform cortex on impulse activity was performed on the same single functionally identified respiratory medullar neurons. A high reactivity of bulbar respiratory neurons on stimulation is established in both studied limbic structures. There is established the qualitatively different character of their response reactions at stimulation of the cortical amygdala nucleus and the periamygdalar cortex. The cortical amygdala nucleus has been shown to produce on the activity of medullar respiratory neurons both facilitating and inhibitory action with predominance of the activating one (without topographical orderliness). The effect of periamygdalar cortex at stimulation of various parts was characterized by topographic differentiation. The suppressing reactions of neurons in the majority of cases were recorded at stimulation of the rostral area of periamygdalar cortex, whereas the excitatory reactions--at stimulation of its caudal part. Functional organization of respiratory control of the studied limbic system structures is discussed.

Interaction between basal ganglia and limbic circuits in learning and memory processes.

PubMed

Calabresi, Paolo; Picconi, Barbara; Tozzi, Alessandro; Ghiglieri, Veronica

2016-01-01

Hippocampus and striatum play distinctive roles in memory processes since declarative and non-declarative memory systems may act independently. However, hippocampus and striatum can also be engaged to function in parallel as part of a dynamic system to integrate previous experience and adjust behavioral responses. In these structures the formation, storage, and retrieval of memory require a synaptic mechanism that is able to integrate multiple signals and to translate them into persistent molecular traces at both the corticostriatal and hippocampal/limbic synapses. The best cellular candidate for this complex synthesis is represented by long-term potentiation (LTP). A common feature of LTP expressed in these two memory systems is the critical requirement of convergence and coincidence of glutamatergic and dopaminergic inputs to the dendritic spines of the neurons expressing this form of synaptic plasticity. In experimental models of Parkinson's disease abnormal accumulation of α-synuclein affects these two memory systems by altering two major synaptic mechanisms underlying cognitive functions in cholinergic striatal neurons, likely implicated in basal ganglia dependent operative memory, and in the CA1 hippocampal region, playing a central function in episodic/declarative memory processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

[The Influence of the Functioning of Brain Regulatory Systems onto the Voluntary Regulation of Cognitive Performance in Children. Report 2. Neuropsychological and Electrophysiological Assessment of Brain Regulatory Functions in Children Aged 10-12 with Learning Difficulties].

PubMed

Semenova, O A; Machinskaya, R I

2015-01-01

A total number of 172 children aged 10-12 were electrophysiologically and neuropsychologically assessed in order to analyze the influence of the functioning of brain regulatory systems onto the voluntary regulation of cognitive performance during the preteen years. EEG patterns associated with the nonoptimal functioning of brain regulatory systems, particularly fronto-thalamic, limbic and fronto-striatal structures were significantly more often observed in children with learning and behavioral difficulties, as compared to the control group. Neuropsychological assessment showed that the nonoptimal functioning of different brain regulatory systems specifically affect the voluntary regulation of cognitive performance. Children with EEG patterns of fronto-thalamic nonoptimal functioning demonstrated poor voluntary regulation such as impulsiveness and difficulties in continuing the same algorithms. Children with EEG patterns of limbic nonoptimal functioning showed a less pronounced executive dysfunction manifested only in poor switching between program units within a task. Children with EEG patterns of fronto-striatal nonoptimal functioning struggled with such executive dysfunctions as motor and tactile perseverations and emotional-motivational deviations such as poor motivation and communicative skills.

Pre-frontal control of closed-loop limbic neurostimulation by rodents using a brain-computer interface

NASA Astrophysics Data System (ADS)

Widge, Alik S.; Moritz, Chet T.

2014-04-01

Objective. There is great interest in closed-loop neurostimulators that sense and respond to a patient's brain state. Such systems may have value for neurological and psychiatric illnesses where symptoms have high intraday variability. Animal models of closed-loop stimulators would aid preclinical testing. We therefore sought to demonstrate that rodents can directly control a closed-loop limbic neurostimulator via a brain-computer interface (BCI). Approach. We trained rats to use an auditory BCI controlled by single units in prefrontal cortex (PFC). The BCI controlled electrical stimulation in the medial forebrain bundle, a limbic structure involved in reward-seeking. Rigorous offline analyses were performed to confirm volitional control of the neurostimulator. Main results. All animals successfully learned to use the BCI and neurostimulator, with closed-loop control of this challenging task demonstrated at 80% of PFC recording locations. Analysis across sessions and animals confirmed statistically robust BCI control and specific, rapid modulation of PFC activity. Significance. Our results provide a preliminary demonstration of a method for emotion-regulating closed-loop neurostimulation. They further suggest that activity in PFC can be used to control a BCI without pre-training on a predicate task. This offers the potential for BCI-based treatments in refractory neurological and mental illness.

The effects of amphetamine exposure on juvenile rats on the neuronal morphology of the limbic system at prepubertal, pubertal and postpubertal ages.

PubMed

Tendilla-Beltrán, Hiram; Arroyo-García, Luis Enrique; Diaz, Alfonso; Camacho-Abrego, Israel; de la Cruz, Fidel; Rodríguez-Moreno, Antonio; Flores, Gonzalo

2016-11-01

Amphetamines (AMPH) are psychostimulants widely used for therapy as well as for recreational purposes. Previous results of our group showed that AMPH exposure in pregnant rats induces physiological and behavioral changes in the offspring at prepubertal and postpubertal ages. In addition, several reports have shown that AMPH are capable of modifying the morphology of neurons in some regions of the limbic system. These modifications can cause some psychiatric conditions. However, it is still unclear if there are changes to behavioral and morphological levels when low doses of AMPH are administered at a juvenile age. The aim of this study was to assess the effect of AMPH administration (1mg/kg) in Sprague-Dawley rats (postnatal day, PD21-PD35) on locomotor activity in a novel environment and compare the neuronal morphology of limbic system areas at three different ages: prepubertal (PD 36), pubertal (PD50) and postpubertal (PD 62). We found that AMPH altered locomotor activity in the prepubertal group, but did not have an effect on the other two age groups. The Golgi-Cox staining method was used to describe the neural morphology of five limbic regions: (Layers 3 and 5) the medial prefrontal cortex (mPFC), the dorsal and ventral hippocampus, the nucleus accumbens and the amygdala, showing that AMPH induced changes at pubertal ages in arborization and spine density of these neurons, but interestingly these changes did not persist at postpubertal ages. Our findings suggest that even early-life AMPH exposure does not induce long-term behavioral and morphological changes, however it causes alterations at pubertal ages in the limbic system networks, a stage of life strongly associated with the development of substance abuse behaviors. Copyright © 2016. Published by Elsevier B.V.

Bipolar disorder: a neural network perspective on a disorder of emotion and motivation.

PubMed

Wessa, Michèle; Kanske, Philipp; Linke, Julia

2014-01-01

Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60-80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD.

Hypersexuality or altered sexual preference following brain injury.

PubMed Central

Miller, B L; Cummings, J L; McIntyre, H; Ebers, G; Grode, M

1986-01-01

Eight patients are described in whom either hypersexuality (four cases) or change in sexual preference (four cases) occurred following brain injury. In this series disinhibition of sexual activity and hypersexuality followed medial basal-frontal or diencephalic injury. This contrasted with the patients demonstrating altered sexual preference whose injuries involved limbic system structures. In some patients altered sexual behaviour may be the presenting or dominant feature of brain injury. Images PMID:3746322

Commonalities in the central nervous system's involvement with complementary medical therapies: limbic morphinergic processes.

PubMed

Esch, Tobias; Guarna, Massimo; Bianchi, Enrica; Zhu, Wei; Stefano, George B

2004-06-01

Currently, complementary and alternative medicine (CAM) are experiencing growing popularity, especially in former industrialized countries. However, most of the underlying physiological and molecular mechanisms as well as participating biological structures are still speculative. Specific and non-specific effects may play a role in CAM. Moreover, trust, belief, and expectation may be of importance, pointing towards common central nervous system (CNS) pathways involved in CAM. Four CAM approaches (acupuncture, meditation, music therapy, and massage therapy) were examined with regard to the CNS activity pattern involved. CNS commonalities between different approaches were investigated. Frontal/prefrontal and limbic brain structures play a role in CAM. Particularly, left-anterior regions of the brain and reward or motivation circuitry constituents are involved, indicating positive affect and emotion-related memory processing--accompanied by endocrinologic and autonomic functions--as crucial components of CAM effects. Thus, trust and belief in a therapist or positive therapy expectations seem to be important. However, besides common non-specific or subjective effects, specific (objective) physiological components also exist. Non-specific CNS commonalities are involved in various CAM therapies. Different therapeutic approaches physiologically overlap in the brain. However, molecular correspondents of the detected CNS analogies still have to be specified. In particular, fast acting autoregulatory signaling molecules presumably play a role. These may also be involved in the placebo response.

[Anti-VGKC antibody-associated limbic encephalitis/Morvan syndrome].

PubMed

Misawa, Tamako; Mizusawa, Hidehiro

2010-04-01

Anti-voltage-gated potassium channel antibodies (anti-VGKC-Ab) cause hyperexcitability of the peripheral nerve and central nervous system. Peripheral nerve hyperexcitability is the chief manifestation of Issacs syndrome and cramp-fasciculation syndrome. Morvan syndrome is characterized by neuromyotonia with autonomic and CNS involvement. Manifestations involving the CNS without peripheral involvement are characteristic of limbic encephalitis and epilepsy. The clinical features of anti-VGKC-Ab-associated limbic encephalitis are subacute onset of episodic memory impairment, disorientation and agitation. Hyponatremia is also noted in most patients. Cortico-steroid therapy, plasma exchange and intravenous immunoglobulin are effective in treating to not only the clinical symptoms but also hyponatremia. Unlike other anti-VGKC-Ab-associated neurological disorders, paraneoplastic cases are rare. Thus, anti-VGKC-Ab-associated limbic encephalopathy is considered to be an autoimmune, non-paraneoplastic, potentially treatable encephalitis. Morvan syndrome is characterized by widespread neurological symptoms involving the peripheral nervous system (neuromyotonia), autonomic system (hyperhidrosis, severe constipation, urinary incontinence, and cardiac arrhythmia) and the CNS (severe insomnia, hallucinations, impairment of short-term memory and epilepsy). Many patients have an underlying tumor, for example thymoma, lung cancer, testicular cancer and lymphoma; this indicates the paraneoplastic nature of the disease. Needle electro-myography reveals myokimic discharge. In nerve conduction study, stimulus-induced repetitive descharges are frequently demonstrated in involved muscles. Plasma exchange is an effective treatment approach, and tumor resection also improves symptoms. Both VGKC-Ab-associated limbic encephalitis and Morvan syndrome can be successfully treated. Therefore, when these diseases are suspected, it's important to measure the anti-VGKC-Ab level.

Brain Structural Effects of Psychopharmacological Treatment in Bipolar Disorder

PubMed Central

McDonald, Colm

2015-01-01

Bipolar disorder is associated with subtle neuroanatomical deficits including lateral ventricular enlargement, grey matter deficits incorporating limbic system structures, and distributed white matter pathophysiology. Substantial heterogeneity has been identified by structural neuroimaging studies to date and differential psychotropic medication use is potentially a substantial contributor to this. This selective review of structural neuroimaging and diffusion tensor imaging studies considers evidence that lithium, mood stabilisers, antipsychotic medication and antidepressant medications are associated with neuroanatomical variation. Most studies are negative and suffer from methodological weaknesses in terms of directly assessing medication effects on neuroanatomy, since they commonly comprise posthoc assessments of medication associations with neuroimaging metrics in small heterogenous patient groups. However the studies which report positive findings tend to form a relatively consistent picture whereby lithium and antiepileptic mood stabiliser use is associated with increased regional grey matter volume, especially in limbic structures. These findings are further supported by the more methodologically robust studies which include large numbers of patients or repeated intra-individual scanning in longitudinal designs. Some similar findings of an apparently ameliorative effect of lithium on white matter microstructure are also emerging. There is less support for an effect of antipsychotic or antidepressant medication on brain structure in bipolar disorder, but these studies are further limited by methodological difficulties. In general the literature to date supports a normalising effect of lithium and mood stabilisers on brain structure in bipolar disorder, which is consistent with the neuroprotective characteristics of these medications identified by preclinical studies. PMID:26412064

Brain Structural Effects of Psychopharmacological Treatment in Bipolar Disorder.

PubMed

McDonald, Colm

2015-01-01

Bipolar disorder is associated with subtle neuroanatomical deficits including lateral ventricular enlargement, grey matter deficits incorporating limbic system structures, and distributed white matter pathophysiology. Substantial heterogeneity has been identified by structural neuroimaging studies to date and differential psychotropic medication use is potentially a substantial contributor to this. This selective review of structural neuroimaging and diffusion tensor imaging studies considers evidence that lithium, mood stabilisers, antipsychotic medication and antidepressant medications are associated with neuroanatomical variation. Most studies are negative and suffer from methodological weaknesses in terms of directly assessing medication effects on neuroanatomy, since they commonly comprise posthoc assessments of medication associations with neuroimaging metrics in small heterogenous patient groups. However the studies which report positive findings tend to form a relatively consistent picture whereby lithium and antiepileptic mood stabiliser use is associated with increased regional grey matter volume, especially in limbic structures. These findings are further supported by the more methodologically robust studies which include large numbers of patients or repeated intra-individual scanning in longitudinal designs. Some similar findings of an apparently ameliorative effect of lithium on white matter microstructure are also emerging. There is less support for an effect of antipsychotic or antidepressant medication on brain structure in bipolar disorder, but these studies are further limited by methodological difficulties. In general the literature to date supports a normalising effect of lithium and mood stabilisers on brain structure in bipolar disorder, which is consistent with the neuroprotective characteristics of these medications identified by preclinical studies.

Paraneoplastic limbic encephalitis presenting as acute viral encephalitis.

PubMed

Kararizou, E; Markou, I; Zalonis, I; Gkiatas, K; Triantafyllou, N; Kararizos, G; Likomanos, D; Zambelis, T; Vassilopoulos, D

2005-11-01

To describe a case of limbic encephalitis which initially presented as viral limbic encephalitis and during the clinical evaluation a renal carcinoma was diagnosed. Patient with history of peripheral paresis of right facial nerve, 1 month after symptoms appearance and treatment, developed fever, vomiting, grand mal seizure, decreased level of consciousness, confusion, hallucinations and agitation. The patient initially presented a clinical picture of viral LE. which confirmed by CSF. MRI brain showed areas with pathological intensity signal in the region of limbic system unilateral. During the clinical evaluation a renal carcinoma was discovered and a nephrectomy has been performed. Although PLE typically presents as a chronic or subacute disease, it may be fulminant and clinically indistinguishable from an acute HSVE. This association pose the problem of a possible relation between this two syndromes and the correct diagnosis is very important, because there are effective treatments.

Are Amygdalar Volume Alterations in Children with Tourette Syndrome Due to ADHD Comorbidity?

ERIC Educational Resources Information Center

Ludolph, Andrea G.; Pinkhardt, Elmar H.; van Elst, Ludger Tebartz; Libal, Gerhard; Ludolph, Albert C.; Fegert, Jorg M.; Kassubek, Jan

2008-01-01

Recent studies have shown that changes in the basal ganglia circuitry and limbic loops may play an important role both in Tourette syndrome (TS) and attention-deficit-hyperactivity disorder (ADHD). This study aimed to investigate in vivo possible morphological alterations of the amygdala as a key component of the limbic system. Amygdalar and total…

Sensitivity of the prefrontal GABAergic system to chronic stress in male and female mice: Relevance for sex differences in stress-related disorders.

PubMed

Shepard, Ryan; Page, Chloe E; Coutellier, Laurence

2016-09-22

Stress-induced modifications of the prefrontal cortex (PFC) are believed to contribute to the onset of mood disorders, such as depression and anxiety, which are more prevalent in women. In depression, the PFC is hypoactive; however the origin of this hypoactivity remains unclear. Possibly, stress could impact the prefrontal GABAergic inhibitory system that, as a result, impairs the functioning of downstream limbic structures controlling emotions. Preclinical evidence indicates that the female PFC is more sensitive to the effects of stress. These findings suggest that exposure to stress could lead to sex-specific alterations in prefrontal GABAergic signaling, which contribute to sex-specific abnormal functioning of limbic regions. These limbic changes could promote the onset of depressive and anxiety behaviors in a sex-specific manner, providing a possible mechanism mediating sex differences in the clinical presentation of stress-related mood disorders. We addressed this hypothesis using a mouse model of stress-induced depressive-like behaviors: the unpredictable chronic mild stress (UCMS) paradigm. We observed changes in prefrontal GABAergic signaling after exposure to UCMS most predominantly in females. Increased parvalbumin (PV) expression and decreased prefrontal neuronal activity were correlated in females with severe emotionality deficit following UCMS, and with altered activity of the amygdala. In males, small changes in emotionality following UCMS were associated with minor changes in prefrontal PV expression, and with hypoactivity of the nucleus accumbens. Our data suggest that prefrontal hypoactivity observed in stress-related mood disorders could result from stress-induced increases in PV expression, particularly in females. This increased vulnerability of the female prefrontal PV system to stress could underlie sex differences in the prevalence and symptomatology of stress-related mood disorders. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Neural correlates of conscious self-regulation of emotion.

PubMed

Beauregard, M; Lévesque, J; Bourgouin, P

2001-09-15

A fundamental question about the relationship between cognition and emotion concerns the neural substrate underlying emotional self-regulation. To address this issue, brain activation was measured in normal male subjects while they either responded in a normal manner to erotic film excerpts or voluntarily attempted to inhibit the sexual arousal induced by viewing erotic stimuli. Results demonstrated that the sexual arousal experienced, in response to the erotic film excerpts, was associated with activation in "limbic" and paralimbic structures, such as the right amygdala, right anterior temporal pole, and hypothalamus. In addition, the attempted inhibition of the sexual arousal generated by viewing the erotic stimuli was associated with activation of the right superior frontal gyrus and right anterior cingulate gyrus. No activation was found in limbic areas. These findings reinforce the view that emotional self-regulation is normally implemented by a neural circuit comprising various prefrontal regions and subcortical limbic structures. They also suggest that humans have the capacity to influence the electrochemical dynamics of their brains, by voluntarily changing the nature of the mind processes unfolding in the psychological space.

Positive reinforcement modulates fronto-limbic systems subserving emotional interference in adolescents.

PubMed

Ladouceur, Cecile D; Schlund, Michael W; Segreti, Anna-Maria

2018-02-15

Fronto-limbic systems play an important role in supporting resistance to emotional distraction to promote goal-directed behavior. Despite evidence that alterations in the functioning of these systems are implicated in developmental trajectories of psychopathology, most studies have been conducted in adults. This study examined the functioning of fronto-limbic systems subserving emotional interference in adolescents and whether differential reinforcement of correct responding can modulate these neural systems in ways that could promote resistance to emotional distraction. Fourteen healthy adolescents (ages 9-15) completed an emotional delayed working memory task during fMRI with emotional distracters (none, neutral, negative) while positive reinforcement (i.e., monetary reward) was provided for correct responses under some conditions. Adolescents showed slightly reduced behavioral performance and greater activation in amygdala and prefrontal cortical regions (ventrolateral, ventromedial, dorsolateral) on correct trials with negative distracters compared to those with no or neutral distracters. Positive reinforcement yielded an overall improvement in accuracy and reaction times and counteracted the effects of negative distracters as evidenced by significant reductions in activation in key fronto-limbic regions. The present findings extend results on emotional interference from adults to adolescents and suggest that positive reinforcement could be used to potentially promote insulation from emotional distraction. A challenge for the future will be to build upon these findings for constructing reinforcement-based attention training programs that could be used to reduce emotional attention biases in anxious youth. Copyright © 2017 Elsevier B.V. All rights reserved.

Regulatory processes of hunger motivated behavior.

PubMed

Lénárd, L; Karádi, Z

2012-01-01

While food intake and body weight are under homeostatic regulation, eating is a highly motivated and reinforced behavior that induces feelings of gratification and pleasure. The chemical senses (taste and odor) and their evaluation are essential to these functions. Brainstem and limbic glucose-monitoring (GM) neurons receiving neurochemical information from the periphery and from the local brain milieu are important controlling hunger motivation, and brain gut peptides have a modulatory role on this function. The hypothalamic and limbic forebrain areas are responsible for evaluation of reward quality and related emotions. They are innervated by the mesolimbic dopaminergic system (MLDS) and majority of GM neurons are also influenced by dopamine. Via dopamine release, the MLDS plays an essential role in rewarding-reinforcing processes of feeding and addiction. The GM network and the MLDS in the limbic system represent essential elements in the neural substrate of motivation.

[Neuroarchitecture of musical emotions].

PubMed

Sel, Alejandra; Calvo-Merino, Beatriz

2013-03-01

The emotional response to music, or musical emotion, is a universal response that draws on diverse psychological processes implemented in a large array of neural structures and mechanisms. Studies using electroencephalography, functional magnetic resonance, lesions and individuals with extent musical training have begun to elucidate some of these mechanisms. The objective of this article is reviewing the most relevant studies that have tried to identify the neural correlates of musical emotion from the more automatic to the more complex processes, and to understand how these correlates interact in the brain. The article describes how the presentation of music perceived as emotional is associated with a rapid autonomic response in thalamic and subthalamic structures, accompanied by changes in the electrodermal and endocrine responses. It also explains how musical emotion processing activates auditory cortex, as well as a series of limbic and paralimbic structures, such as the amygdala, the anterior cingulate cortex or the hippocampus, demonstrating the relevant contribution of the limbic system to musical emotion. Further, it is detailed how musical emotion depends to a great extent on semantic and syntactic process carried out in temporal and parietofrontal areas, respectively. Some of the recent works demonstrating that musical emotion highly relies on emotional simulation are also mentioned. Finally, a summary of these studies, their limitations, and suggestions for further research on the neuroarchitecture of musical emotion are given.

Neural control of chronic stress adaptation

PubMed Central

Herman, James P.

2013-01-01

Stress initiates adaptive processes that allow the organism to physiologically cope with prolonged or intermittent exposure to real or perceived threats. A major component of this response is repeated activation of glucocorticoid secretion by the hypothalamo-pituitary-adrenocortical (HPA) axis, which promotes redistribution of energy in a wide range of organ systems, including the brain. Prolonged or cumulative increases in glucocorticoid secretion can reduce benefits afforded by enhanced stress reactivity and eventually become maladaptive. The long-term impact of stress is kept in check by the process of habituation, which reduces HPA axis responses upon repeated exposure to homotypic stressors and likely limits deleterious actions of prolonged glucocorticoid secretion. Habituation is regulated by limbic stress-regulatory sites, and is at least in part glucocorticoid feedback-dependent. Chronic stress also sensitizes reactivity to new stimuli. While sensitization may be important in maintaining response flexibility in response to new threats, it may also add to the cumulative impact of glucocorticoids on the brain and body. Finally, unpredictable or severe stress exposure may cause long-term and lasting dysregulation of the HPA axis, likely due to altered limbic control of stress effector pathways. Stress-related disorders, such as depression and PTSD, are accompanied by glucocorticoid imbalances and structural/ functional alterations in limbic circuits that resemble those seen following chronic stress, suggesting that inappropriate processing of stressful information may be part of the pathological process. PMID:23964212

Extra-hippocampal subcortical limbic involvement predicts episodic recall performance in multiple sclerosis.

PubMed

Dineen, Robert A; Bradshaw, Christopher M; Constantinescu, Cris S; Auer, Dorothee P

2012-01-01

Episodic memory impairment is a common but poorly-understood phenomenon in multiple sclerosis (MS). We aim to establish the relative contributions of reduced integrity of components of the extended hippocampal-diencephalic system to memory performance in MS patients using quantitative neuroimaging. 34 patients with relapsing-remitting MS and 24 healthy age-matched controls underwent 3 T MRI including diffusion tensor imaging and 3-D T1-weighted volume acquisition. Manual fornix regions-of-interest were used to derive fornix fractional anisotropy (FA). Normalized hippocampal, mammillary body and thalamic volumes were derived by manual segmentation. MS subjects underwent visual recall, verbal recall, verbal recognition and verbal fluency assessment. Significant differences between MS patients and controls were found for fornix FA (0.38 vs. 0.46, means adjusted for age and fornix volume, P<.0005) and mammillary body volumes (age-adjusted means 0.114 ml vs. 0.126 ml, P<.023). Multivariate regression analysis identified fornix FA and mammillary bodies as predictor of visual recall (R(2) = .31, P = .003, P = .006), and thalamic volume as predictive of verbal recall (R(2) = .37, P<.0005). No limbic measures predicted verbal recognition or verbal fluency. These findings indicate that structural and ultrastructural alterations in subcortical limbic components beyond the hippocampus predict performance of episodic recall in MS patients with mild memory dysfunction.

The auditory cortex hosts network nodes influential for emotion processing: An fMRI study on music-evoked fear and joy

PubMed Central

Skouras, Stavros; Lohmann, Gabriele

2018-01-01

Sound is a potent elicitor of emotions. Auditory core, belt and parabelt regions have anatomical connections to a large array of limbic and paralimbic structures which are involved in the generation of affective activity. However, little is known about the functional role of auditory cortical regions in emotion processing. Using functional magnetic resonance imaging and music stimuli that evoke joy or fear, our study reveals that anterior and posterior regions of auditory association cortex have emotion-characteristic functional connectivity with limbic/paralimbic (insula, cingulate cortex, and striatum), somatosensory, visual, motor-related, and attentional structures. We found that these regions have remarkably high emotion-characteristic eigenvector centrality, revealing that they have influential positions within emotion-processing brain networks with “small-world” properties. By contrast, primary auditory fields showed surprisingly strong emotion-characteristic functional connectivity with intra-auditory regions. Our findings demonstrate that the auditory cortex hosts regions that are influential within networks underlying the affective processing of auditory information. We anticipate our results to incite research specifying the role of the auditory cortex—and sensory systems in general—in emotion processing, beyond the traditional view that sensory cortices have merely perceptual functions. PMID:29385142

Impulsive aggression and response inhibition in attention-deficit/hyperactivity disorder and disruptive behavioral disorders: Findings from a systematic review.

PubMed

Puiu, Andrei A; Wudarczyk, Olga; Goerlich, Katharina S; Votinov, Mikhail; Herpertz-Dahlmann, Beate; Turetsky, Bruce; Konrad, Kerstin

2018-04-22

Although impulsive aggression (IA) and dysfunctional response inhibition (RI) are hallmarks of attention-deficit/hyperactivity disorder (ADHD) and disrupted behavioral disorders (DBDs), little is known about their shared and distinct deviant neural mechanisms. Here, we selectively reviewed s/fMRI ADHD and DBD studies to identify disorder-specific and shared IA and RI aberrant neural mechanisms. In ADHD, deviant prefrontal and cingulate functional activity was associated with increased IA. Structural alterations were most pronounced in the cingulate cortex. Subjects with DBDs showed marked cortico-subcortical dysfunctions. ADHD and DBDs share similar cortico-limbic structural and functional alterations. RI deficits in ADHD highlighted hypoactivity in the dorso/ventro-lateral PFC, insula, and striatum, while the paralimbic system was primarily dysfunctional in DBDs. Across disorders, extensively altered cortico-limbic dysfunctions underlie IA, while RI was mostly associated with aberrant prefrontal activity. Control network deficits were evidenced across clinical phenotypes in IA and RI. Dysfunctions at any level within these cortico-subcortical projections lead to deficient cognitive-affective control by ascribing emotional salience to otherwise irrelevant stimuli. The clinical implications of these findings are discussed. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Aberrant topological patterns of brain structural network in temporal lobe epilepsy.

PubMed

Yasuda, Clarissa Lin; Chen, Zhang; Beltramini, Guilherme Coco; Coan, Ana Carolina; Morita, Marcia Elisabete; Kubota, Bruno; Bergo, Felipe; Beaulieu, Christian; Cendes, Fernando; Gross, Donald William

2015-12-01

Although altered large-scale brain network organization in patients with temporal lobe epilepsy (TLE) has been shown using morphologic measurements such as cortical thickness, these studies, have not included critical subcortical structures (such as hippocampus and amygdala) and have had relatively small sample sizes. Here, we investigated differences in topological organization of the brain volumetric networks between patients with right TLE (RTLE) and left TLE (LTLE) with unilateral hippocampal atrophy. We performed a cross-sectional analysis of 86 LTLE patients, 70 RTLE patients, and 116 controls. RTLE and LTLE groups were balanced for gender (p = 0.64), seizure frequency (Mann-Whitney U test, p = 0.94), age (p = 0.39), age of seizure onset (p = 0.21), and duration of disease (p = 0.69). Brain networks were constructed by thresholding correlation matrices of volumes from 80 cortical/subcortical regions (parcellated with Freesurfer v5.3 https://surfer.nmr.mgh.harvard.edu/) that were then analyzed using graph theoretical approaches. We identified reduced cortical/subcortical connectivity including bilateral hippocampus in both TLE groups, with the most significant interregional correlation increases occurring within the limbic system in LTLE and contralateral hemisphere in RTLE. Both TLE groups demonstrated less optimal topological organization, with decreased global efficiency and increased local efficiency and clustering coefficient. LTLE also displayed a more pronounced network disruption. Contrary to controls, hub nodes in both TLE groups were not distributed across whole brain, but rather found primarily in the paralimbic/limbic and temporal association cortices. Regions with increased centrality were concentrated in occipital lobes for LTLE and contralateral limbic/temporal areas for RTLE. These findings provide first evidence of altered topological organization of the whole brain volumetric network in TLE, with disruption of the coordinated patterns of cortical/subcortical morphology. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

An iontophoretic survey of opioid peptide actions in the rat limbic system: in search of opiate epileptogenic mechanisms.

PubMed

French, E D; Siggins, G R

1980-10-01

Iontophoretic and micropressure drug application and lesion techniques were used to investigate the cellular source of rat limbic system epileptiform responses to opioid peptides [19]. Iontophoretically applied morphine, methionine enkephalin or beta-endorphin inhibited the spontaneous or glutamate-activated firing of the great majority of single neurons in medial and lateral septum, amygdala and cingulate cortex. These inhibitions in firing were antagonized by iontophoresis of naloxone. In contrast to inhibitory effects in other limbic areas, morphine and the opioid peptides predominantly excited CA1 and CA3 pyramidal neurons in a naloxone-sensitive manner, as previously reported [36]. On rare occasions, iontophoretically applied beta-endorphin evoked repetitive waveforms similar to interictal population EPSPs or spikes. Micropressure application of opiates and peptides also excited hippocampal neurons indicating such responses were not current-induced artefacts. The possible role of the excitatory cholinergic septal hippocampal pathway in the facilitatory response of hippocampal units to the opiates was tested with iontophoretically applied atropine and scopolamine, or lesions of septal nuclei. None of these manipulations reduced the opioid-induced excitations; rather, septal lesions enhanced excitatory and epileptiform responses to the opiates. These results support the hypothesis that opiate-evoked epileptiform activity in the limbic system arises from enhanced pyramidal cell activity in the hippocampal formation, probably by a non-cholinergic mechanism.

SOBP Is Mutated in Syndromic and Nonsyndromic Intellectual Disability and Is Highly Expressed in the Brain Limbic System

PubMed Central

Birk, Efrat; Har-Zahav, Adi; Manzini, Chiara M.; Pasmanik-Chor, Metsada; Kornreich, Liora; Walsh, Christopher A.; Noben-Trauth, Konrad; Albin, Adi; Simon, Amos J.; Colleaux, Laurence; Morad, Yair; Rainshtein, Limor; Tischfield, David J.; Wang, Peter; Magal, Nurit; Maya, Idit; Shoshani, Noa; Rechavi, Gideon; Gothelf, Doron; Maydan, Gal; Shohat, Mordechai; Basel-Vanagaite, Lina

2010-01-01

Intellectual disability (ID) affects 1%–3% of the general population. We recently reported on a family with autosomal-recessive mental retardation with anterior maxillary protrusion and strabismus (MRAMS) syndrome. One of the reported patients with ID did not have dysmorphic features but did have temporal lobe epilepsy and psychosis. We report on the identification of a truncating mutation in the SOBP that is responsible for causing both syndromic and nonsyndromic ID in the same family. The protein encoded by the SOBP, sine oculis binding protein ortholog, is a nuclear zinc finger protein. In mice, Sobp (also known as Jxc1) is critical for patterning of the organ of Corti; one of our patients has a subclinical cochlear hearing loss but no gross cochlear abnormalities. In situ RNA expression studies in postnatal mouse brain showed strong expression in the limbic system at the time interval of active synaptogenesis. The limbic system regulates learning, memory, and affective behavior, but limbic circuitry expression of other genes mutated in ID is unusual. By comparing the protein content of the +/jc to jc/jc mice brains with the use of proteomics, we detected 24 proteins with greater than 1.5-fold differences in expression, including two interacting proteins, dynamin and pacsin1. This study shows mutated SOBP involvement in syndromic and nonsyndromic ID with psychosis in humans. PMID:21035105

Differential glutamatergic modulation of monoamine release in the limbic lobe by selective anticonvulsant ionotropic and metabotropic glutamate receptor ligands.

PubMed

Smolders, I

2005-01-01

Several researchers are currently trying to unravel neurobiological relationships between epilepsy and depression. After all, these disorders often develop in the same vulnerable brain regions and the importance of comorbid depression and epilepsy is still underscored. Facilitation of central serotonin (5-HT), dopamine (DA) and noradrenaline (NAD) release seems to be associated with both anticonvulsant and antidepressant effects. We show that selective ionotropic and metabotropic glutamate receptor ligands with anticonvulsant properties differentially modulate NAD, DA and 5-HT in rat limbic lobe structures.

Limbic hyperconnectivity in the vegetative state.

PubMed

Di Perri, Carol; Bastianello, Stefano; Bartsch, Andreas J; Pistarini, Caterina; Maggioni, Giorgio; Magrassi, Lorenzo; Imberti, Roberto; Pichiecchio, Anna; Vitali, Paolo; Laureys, Steven; Di Salle, Francesco

2013-10-15

To investigate functional connectivity between the default mode network (DMN) and other networks in disorders of consciousness. We analyzed MRI data from 11 patients in a vegetative state and 7 patients in a minimally conscious state along with age- and sex-matched healthy control subjects. MRI data analysis included nonlinear spatial normalization to compensate for disease-related anatomical distortions. We studied brain connectivity data from resting-state MRI temporal series, combining noninferential (independent component analysis) and inferential (seed-based general linear model) methods. In DMN hypoconnectivity conditions, a patient's DMN functional connectivity shifts and paradoxically increases in limbic structures, including the orbitofrontal cortex, insula, hypothalamus, and the ventral tegmental area. Concurrently with DMN hypoconnectivity, we report limbic hyperconnectivity in patients in vegetative and minimally conscious states. This hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops, which, in turn, could disrupt normal patterns of connectivity.

Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion.

PubMed

Eisner, Patrick; Klasen, Martin; Wolf, Dhana; Zerres, Klaus; Eggermann, Thomas; Eisert, Albrecht; Zvyagintsev, Mikhail; Sarkheil, Pegah; Mathiak, Krystyna A; Zepf, Florian; Mathiak, Klaus

2017-03-01

A gene-environment interaction between expression genotypes of the monoamine oxidase A (MAOA) and adverse childhood experience increases the risk of antisocial behavior. However, the neural underpinnings of this interaction remain uninvestigated. A cortico-limbic circuit involving the prefrontal cortex (PFC) and the amygdala is central to the suppression of aggressive impulses and is modulated by serotonin (5-HT). MAOA genotypes may modulate the vulnerability of this circuit and increase the risk for emotion regulation deficits after specific life events. Acute tryptophan depletion (ATD) challenges 5-HT regulation and may identify vulnerable neuronal circuits, contributing to the gene-environment interaction. Functional magnetic resonance imaging measured the resting-state state activity in 64 healthy males in a double-blind, placebo-controlled study. Cortical maps of amygdala correlation identified the impact of ATD and its interaction with low- (MAOA-L) and high-expression variants (MAOA-H) of MAOA on cortico-limbic connectivity. Across all Regions of Interest (ROIs) exhibiting an ATD effect on cortico-limbic connectivity, MAOA-L carriers were more susceptible to ATD than MAOA-H carriers. In particular, the MAOA-L group exhibited a larger reduction of amygdala connectivity with the right prefrontal cortex and a larger increase of amygdala connectivity with the insula and dorsal PCC. MAOA-L carriers were more susceptable to a central 5-HT challenge in cortico-limbic networks. Such vulnerability of the cortical serotonergic system may contribute to the emergence of antisocial behavior after systemic challenges, observed as gene-environment interaction. Hum Brain Mapp 38:1622-1635, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Different patterns of local field potentials from limbic DBS targets in patients with major depressive and obsessive compulsive disorder

PubMed Central

Neumann, W-J; Huebl, J; Brücke, C; Gabriëls, L; Bajbouj, M; Merkl, A; Schneider, G-H; Nuttin, B; Brown, P; Kühn, AA

2016-01-01

The role of distinct limbic areas in emotion regulation has been largely inferred from neuroimaging studies. Recently, the opportunity for intracranial recordings from limbic areas has arisen in patients undergoing deep brain stimulation (DBS) for neuropsychiatric disorders including major depressive disorder (MDD) and obsessive compulsive disorder (OCD). Here we test the hypothesis that distinct temporal patterns of local field potential (LFP) activity in the human limbic system reflect disease state and symptom severity in MDD and OCD patients. To this end, we recorded LFPs via implanted DBS electrodes from the bed nucleus of stria terminalis (BNST area) in 12 patients (5 OCD, 7 MDD) and from the subgenual cingulate cortex in 7 MDD patients (CG25 area). We found a distinct pattern of oscillatory activity with significantly higher α-power in MDD compared with OCD in the BNST area (broad α-band 8–14 Hz; P<0.01) and a similar level of α-activity in the CG25 area as in the BNST area in MDD patients. The mean α-power correlated with severity of depressive symptoms as assessed by the Beck depression inventory in MDD (n = 14, r = 0.55, P = 0.042) but not with severity of obsessive compulsive symptoms in OCD. Here we show larger α-band activity in MDD patients compared with OCD recorded from intracranial DBS targets. Our results suggest that α-activity in the limbic system may be a signature of symptom severity in MDD and may serve as a potential state biomarker for closed loop DBS in MDD. PMID:24514569

Diffusion Imaging of Auditory and Auditory-Limbic Connectivity in Tinnitus: Preliminary Evidence and Methodological Challenges

PubMed Central

Seydell-Greenwald, Anna; Raven, Erika P.; Leaver, Amber M.; Turesky, Ted K.; Rauschecker, Josef P.

2014-01-01

Subjective tinnitus, or “ringing in the ears,” is perceived by 10 to 15 percent of the adult population and causes significant suffering in a subset of patients. While it was originally thought of as a purely auditory phenomenon, there is increasing evidence that the limbic system influences whether and how tinnitus is perceived, far beyond merely determining the patient's emotional reaction to the phantom sound. Based on functional imaging and electrophysiological data, recent articles frame tinnitus as a “network problem” arising from abnormalities in auditory-limbic interactions. Diffusion-weighted magnetic resonance imaging is a noninvasive method for investigating anatomical connections in vivo. It thus has the potential to provide anatomical evidence for the proposed changes in auditory-limbic connectivity. However, the few diffusion imaging studies of tinnitus performed to date have inconsistent results. In the present paper, we briefly summarize the results of previous studies, aiming to reconcile their results. After detailing analysis methods, we then report findings from a new dataset. We conclude that while there is some evidence for tinnitus-related increases in auditory and auditory-limbic connectivity that counteract hearing-loss related decreases in auditory connectivity, these results should be considered preliminary until several technical challenges have been overcome. PMID:25050181

Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders.

PubMed

Arnsten, Amy F T; Rubia, Katya

2012-04-01

This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies. The PFC provides "top-down" regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention. Altogether, there is a good correspondence between anatomical circuitry mediating compromised functions and patterns of brain structure and function changes in children with neuropsychiatric disorders. Medications may optimize the neurochemical environment in PFC and associated circuitries, and improve structure and function. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

PubMed Central

Goldstein, Rita Z.; Volkow, Nora D.

2005-01-01

Objective Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. Method An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. Results The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to track, update, and modulate the salience of a reinforcer as a function of context and expectation and the ability to control and inhibit prepotent responses. Conclusions These results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervaluing of alternative reinforcers, and deficits in inhibitory control for drug responses. These changes in addiction, which the authors call I-RISA (impaired response inhibition and salience attribution), expand the traditional concepts of drug dependence that emphasize limbic-regulated responses to pleasure and reward. PMID:12359667

Is the spatial distribution of brain lesions associated with closed-head injury in children predictive of subsequent development of posttraumatic stress disorder?

NASA Technical Reports Server (NTRS)

Herskovits, Edward H.; Gerring, Joan P.; Davatzikos, Christos; Bryan, R. Nick

2002-01-01

PURPOSE: To determine whether there is an association between the spatial distributions of lesions detected at magnetic resonance (MR) imaging of the brain in children, adolescents, and young adults after closed-head injury (CHI) and development of the reexperiencing symptoms of posttraumatic stress disorder (PTSD). MATERIALS AND METHODS: Data obtained in 94 subjects without a history of PTSD as determined by parental interview were analyzed. MR images were obtained 3 months after CHI. Lesions were manually delineated and registered to the Talairach coordinate system. Mann-Whitney analysis of lesion distribution and PTSD status at 1 year (again, as determined by parental interview) was performed, consisting of an analysis of lesion distribution versus the major symptoms of PTSD: reexperiencing, hyperarousal, and avoidance. RESULTS: Of the 94 subjects, 41 met the PTSD reexperiencing criterion and nine met all three PTSD criteria. Subjects who met the reexperiencing criterion had fewer lesions in limbic system structures (eg, the cingulum) on the right than did subjects who did not meet this criterion (Mann-Whitney, P =.003). CONCLUSION: Lesions induced by CHI in the limbic system on the right may inhibit subsequent manifestation of PTSD reexperiencing symptoms in children, adolescents, and young adults. Copyright RSNA, 2002.

[The functional state classification and evaluation of the stability level in mental loads based on the factor structure of heart rate variability parameters].

PubMed

Mashin, V A; Mashina, M N

2004-12-01

In the paper, outcomes of the researches devoted to factor analysis of heart rate variability parameters and definition of the most informative parameters for diagnostics of functional states and an evaluation of level of stability to mental loads, are presented. The factor structure of parameters, which unclude integral level of heart rate variability (1), balance between activity of vagus and brain cortical-limbic systems (2), integrated level of cardiovascular system functioning (3), is substantiated. Factor analysis outcomes have been used for construction of functional state classification, for their differential diagnostics, and for development and check of algorithm for evaluation of the stability level in mental loads.

Violence, mental illness, and the brain – A brief history of psychosurgery: Part 2 – From the limbic system and cingulotomy to deep brain stimulation

PubMed Central

Faria, Miguel A.

2013-01-01

Knowledge of neuroscience flourished during and in the wake of the era of frontal lobotomy, as a byproduct of psychosurgery in the late 1930s and 1940s, revealing fascinating neural pathways and neurophysiologic mechanisms of the limbic system for the formulation of emotions, memory, and human behavior. The creation of the Klüver-Bucy syndrome in monkeys opened new horizons in the pursuit of knowledge in human behavior and neuropathology. In the 1950s specialized functional neurosurgery was developed in association with stereotactic neurosurgery; deep brain electrodes were implanted for more precise recording of brain electrical activity in the evaluation and treatment of intractable mental disorders, including schizophrenia, “pathologic aggression,” and psychomotor seizures in temporal lobe epilepsy. Psychosurgical procedures involved deep brain stimulation of the limbic system, as well as ablative procedures, such as cingulotomy and thalamotomy. The history of these developments up to the 21st century will continue in this three-part essay-editorial, exclusively researched and written for the readers of Surgical Neurology International. PMID:23776761

Manual morphometry of hippocampus and amygdala in adults with attention-deficit hyperactivity disorder.

PubMed

Nickel, Kathrin; Tebartz van Elst, Ludger; Perlov, Evgeniy; Jitten-Schachenmeier, Renate; Beier, Daniel; Endres, Dominique; Goll, Peter; Philipsen, Alexandra; Maier, Simon

2017-09-30

Previous studies have pointed to the involvement of limbic structures in the genesis of attention deficit hyperactivity disorder (ADHD). The present researchers manually segmented magnetic resonance images of 30 individuals with ADHD and 30 individually matched controls, focusing on amygdala and hippocampus volumes. Neither hippocampus nor amygdala volume differed significantly between individuals with and without ADHD. However, ADHD patients with higher hyperactivity scores had significantly smaller left amygdala volumes. This finding suggests that limbic alterations are significant in hyperactive symptoms in the pathophysiology of ADHD. Copyright © 2017. Published by Elsevier B.V.

Progressive neurostructural changes in adolescent and adult patients with bipolar disorder.

PubMed

Lisy, Megan E; Jarvis, Kelly B; DelBello, Melissa P; Mills, Neil P; Weber, Wade A; Fleck, David; Strakowski, Stephen M; Adler, Caleb M

2011-06-01

Several lines of evidence suggest that bipolar disorder is associated with progressive changes in gray matter volume (GMV), particularly in brain structures involved in emotional regulation and expression. The majority of these studies however, have been cross-sectional in nature. In this study we compared baseline and follow-up scans in groups of bipolar disorder and healthy subjects. We hypothesized bipolar disorder subjects would demonstrate significant GMV changes over time. A total of 58 bipolar disorder and 48 healthy subjects participated in structural magnetic resonance imaging (MRI). Subjects were rescanned 3-34 months after their baseline MRI. MRI images were segmented, normalized to standard stereotactic space, and compared voxel-by-voxel using statistical parametrical mapping software (SPM2). A model was developed to investigate differences in GMV at baseline, and associated with time and episodes, as well as in comparison to healthy subjects. We observed increases in GMV in bipolar disorder subjects across several brain regions at baseline and over time, including portions of the prefrontal cortex as well as limbic and subcortical structures. Time-related changes differed to some degree between adolescent and adult bipolar disorder subjects. The interval between scans positively correlated with GMV increases in bipolar disorder subjects in portions of the prefrontal cortex, and both illness duration and number of depressive episodes were associated with increased GMV in subcortical and limbic structures. Our findings support suggestions that widely observed progressive neurofunctional changes in bipolar disorder patients may be related to structural brain abnormalities in anterior limbic structures. Abnormalities largely involve regions previously noted to be integral to emotional expression and regulation, and appear to vary by age. © 2011 John Wiley and Sons A/S.

Local Brain Activity Differences Between Herpes Zoster and Postherpetic Neuralgia Patients: A Resting-State Functional MRI Study.

PubMed

Cao, Song; Li, Ying; Deng, Wenwen; Qin, Bangyong; Zhang, Yi; Xie, Peng; Yuan, Jie; Yu, Buwei; Yu, Tian

2017-07-01

Herpes zoster (HZ) can develop into postherpetic neuralgia (PHN), both of which are painful diseases. PHN patients suffer chronic pain and emotional disorders. Previous studies showed that the PHN brain displayed abnormal activity and structural change, but the difference in brain activity between HZ and PHN is still not known. To identify regional brain activity changes in HZ and PHN brains with resting-state functional magnetic resonance imaging (rs-fMRI) technique, and to observe the differences between HZ and PHN patients. Observational study. University hospital. Regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) methods were employed to analysis resting-state brain activity. Seventy-three age and gender matched patients (50 HZ, 23 PHN) and 55 healthy controls were enrolled. ReHo and fALFF changes were analyzed to detect the functional abnormality in HZ and PHN brains. Compared with healthy controls, HZ and PHN patients exhibited abnormal ReHo and fALFF values in classic pain-related brain regions (such as the frontal lobe, thalamus, insular, and cerebellum) as well as the brainstem, limbic lobe, and temporal lobe. When HZ developed to PHN, the activity in the vast area of the cerebellum significantly increased while that of some regions in the occipital lobe, temporal lobe, parietal lobe, and limbic lobe showed an apparent decrease. (a) Relatively short pain duration (mean 12.2 months) and small sample size (n = 23) for PHN group. (b) Comparisons at different time points (with paired t-tests) for each patient may minimize individual differences. HZ and PHN induced local brain activity changed in the pain matrix, brainstem, and limbic system. HZ chronification induced functional change in the cerebellum, occipital lobe, temporal lobe, parietal lobe, and limbic lobe. These brain activity changes may be correlated with HZ-PHN transition. Herpes zoster, postherpetic neuralgia, resting-state fMRI (rs-fMRI), regional homogeneity (ReHo), fractional aptitude of low-frequency fluctuation (fALFF).

Comparing Neural Correlates of REM Sleep in Posttraumatic Stress Disorder and Depression: A Neuroimaging Study

PubMed Central

Ebdlahad, Sommer; Nofzinger, Eric A.; James, Jeffrey A.; Buysse, Daniel J.; Price, Julie C.; Germain, Anne

2013-01-01

Rapid eye movement (REM) sleep disturbances predict poor clinical outcomes in posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). In MDD, REM sleep is characterized by activation of limbic and paralimbic brain regions compared to wakefulness. The neural correlates of PTSD during REM sleep remain scarcely explored, and comparisons of PTSD and MDD have not been conducted. The present study sought to compare brain activity patterns during wakefulness and REM sleep in 13 adults with PTSD and 12 adults with MDD using [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (PET). PTSD was associated with greater increases in relative regional cerebral metabolic rate of glucose (rCMRglc) in limbic and paralimbic structures in REM sleep compared to wakefulness. Post-hoc comparisons indicated that MDD was associated with greater limbic and paralimbic rCMRglc during wakefulness but not REM sleep compared to PTSD. Our findings suggest that PTSD is associated with increased REM sleep limbic and paralimbic metabolism, whereas MDD is associated with wake and REM hypermetabolism in these areas. These observations suggest that PTSD and MDD disrupt REM sleep through different neurobiological processes. Optimal sleep treatments between the two disorders may differ: REM-specific therapy may be more effective in PTSD. PMID:24367137

Similar increases in extracellular lactic acid in the limbic system during epileptic and/or olfactory stimulation.

PubMed

Fornai, F; Bassi, L; Gesi, M; Giorgi, F S; Guerrini, R; Bonaccorsi, I; Alessandrì, M G

2000-01-01

Previous studies have shown that physiological stimulation of brain activity increases anaerobic glucose consumption, both in humans and in experimental animals. To investigate this phenomenon further, we measured extracellular lactate levels within different rat brain regions, using microdialysis. Experiments were performed comparing the effects of natural, physiological olfactory stimulation of the limbic system with experimental limbic seizures. Olfactory stimulation was carried out by using different odors (i.e. both conventional odors: 2-isobutyl-3-methoxypyrazine, green pepper essence; thymol; and 2-sec-butylthiazoline, a sexual pheromone). Limbic seizures were either induced by systemic injection of pilocarpine (200-400 mg/kg) or focally elicited by microinfusions of chemoconvulsants (bicuculline 118 pmol and cychlothiazide 1.2 nmol) within the anterior piriform cortex. Seizures induced by systemic pilocarpine tripled lactic acid within the hippocampus, whereas limbic seizures elicited by focal microinfusion of chemoconvulsants within the piriform cortex produced a less pronounced increase in extracellular lactic acid. Increases in extracellular lactate occurring during olfactory stimulation with the sexual pheromone (three times the baseline levels) were non-significantly different from those occurring after systemic pilocarpine. Increases in lactic acid following natural olfactory stimulation were abolished both by olfactory bulbectomy and by the focal microinfusion of tetrodotoxin, while they were significantly attenuated by the local application of the N-methyl-D-aspartate antagonist AP-5. Increases in hippocampal lactate induced by short-lasting stimuli (olfactory stimulation or microinfusion of subthreshold doses of chemoconvulsants, bicuculline 30 pmol) were reproducible after a short delay (1 h) and cumulated when applied sequentially. In contrast, limbic status epilepticus led to a long-lasting refractoriness to additional lactate-raising stimuli and there was no further increase in lactate levels when the olfactory stimulation was produced during status epilepticus. Increases in lactic acid following olfactory stimulation occurred with site specificity in the rhinencephalon (hippocampus, piriform and entorhinal cortex) but not in the dorsal striatum. Site specificity crucially relied on the quality of the stimulus. For instance, other natural stimuli (i.e. tail pinch) produced a similar increase in extracellular lactate in all brain areas under investigation. The major conclusion of this work is that the presentation of an odor known to be a rat pheromone results in lactate production as great as that induced by the systemic convulsant pylocarpine (maximum: 2.286+/-0.195 mM and 1.803+/-0.108 mM, respectively). This supports the notion that the great magnitude of lactate production known to accompany seizures can result from the intensified neural activity per se ("aerobic gycolysis"), not merely from local anoxia or other pathological changes.

An initial MRI picture of limbic encephalitis in subacute sclerosing panencephalitis.

PubMed

Lebon, Sébastien; Maeder, Philippe; Maeder-Ingvar, Malin; Poloni, Claudia; Mayor-Dubois, Claire; Roulet-Perez, Eliane; Jeannet, Pierre-Yves

2011-11-01

Subacute sclerosing panencephalitis (SSPE) is a rare and severe long-term complication of measles. Hallmarks of this entity include progressive cognitive decline, myoclonia, a generalized periodic pattern on EEG and deep white matter abnormalities on MRI. However, imaging can be normal in early stages. We report herein the case of a previously healthy 13-years-old girl with an unusual radiological presentation. She presented with unilateral myoclonia, cognitive decline with memory impairment and a first brain MRI with swelling of both hippocampi mimicking limbic encephalitis. Measles antibodies were positive in CSF and the EEG showed slow periodic complexes. This unusual radiological presentation has never been described in SSPE. Relationship between virus and limbic system are discussed. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Structural and functional connectivity changes in the brain associated with shyness but not with social anxiety.

PubMed

Yang, Xun; Kendrick, Keith Maurice; Wu, Qizhu; Chen, Taolin; Lama, Sunima; Cheng, Bochao; Li, Shiguang; Huang, Xiaoqi; Gong, Qiyong

2013-01-01

Shyness and social anxiety are correlated to some extent and both are associated with hyper-responsivity to social stimuli in the frontal cortex and limbic system. However to date no studies have investigated whether common structural and functional connectivity differences in the brain may contribute to these traits. We addressed this issue in a cohort of 61 healthy adult subjects. Subjects were first assessed for their levels of shyness (Cheek and Buss Shyness scale) and social anxiety (Liebowitz Social Anxiety scale) and trait anxiety. They were then given MRI scans and voxel-based morphometry and seed-based, resting-state functional connectivity analysis investigated correlations with shyness and anxiety scores. Shyness scores were positively correlated with gray matter density in the cerebellum, bilateral superior temporal gyri and parahippocampal gyri and right insula. Functional connectivity correlations with shyness were found between the superior temporal gyrus, parahippocampal gyrus and the frontal gyri, between the insula and precentral gyrus and inferior parietal lobule, and between the cerebellum and precuneus. Additional correlations were found for amygdala connectivity with the medial frontal gyrus, superior frontal gyrus and inferior parietal lobule, despite the absence of any structural correlation. By contrast no structural or functional connectivity measures correlated with social or trait anxiety. Our findings show that shyness is specifically associated with structural and functional connectivity changes in cortical and limbic regions involved with processing social stimuli. These associations are not found with social or trait anxiety in healthy subjects despite some behavioral correlations with shyness.

Carbachol-induced network oscillations in an in vitro limbic system brain slice.

PubMed

Lévesque, Maxime; Cataldi, Mauro; Chen, Li-Yuan; Hamidi, Shabnam; Avoli, Massimo

2017-04-21

We employed simultaneous field potential recordings from CA3, subiculum and entorhinal cortex in an in vitro brain slice preparation to understand the involvement of these limbic areas in the generation of the field potential oscillations that are induced by bath application of the muscarinic receptor agonist carbachol. Regularly spaced oscillations that mainly presented at theta frequency range (5-12Hz) occurred synchronously in all three structures in the presence of carbachol. These oscillations, which disappeared when slices were perfused with pirenzepine or with glutamatergic receptor antagonists, were categorized as short (<4s) and long (>4s) with short events oscillating at higher frequencies than long events. Field oscillations were highly synchronized between regions and latency analysis revealed that they often initiated in the entorhinal cortex later than in the other two structures. Blocking GABA A receptors modified the activity patterns of both short and long oscillations and decreased their coherence in the theta frequency range. Finally, blocking KCC2 activity disclosed a pattern of recurrent short oscillations. Our results suggest that in the presence of carbachol both subiculum and CA3 most often drive theta generators in the entorhinal cortex and that these oscillations are influenced but not abolished by altering GABA A receptor signaling. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration.

PubMed

Lu, Yi; Shen, Zonglin; Cheng, Yuqi; Yang, Hui; He, Bo; Xie, Yue; Wen, Liang; Zhang, Zhenguang; Sun, Xuejin; Zhao, Wei; Xu, Xiufeng; Han, Dan

2017-01-01

It is crucial to explore the pathogenesis of major depressive disorder (MDD) at the early stage for the better diagnostic and treatment strategies. It was suggested that MDD might be involving in functional or structural alternations at the brain network level. However, at the onset of MDD, whether the whole brain white matter (WM) alterations at network level are already evident still remains unclear. In the present study, diffusion MRI scanning was adopt to depict the unique WM structural network topology across the entire brain at the early stage of MDD. Twenty-one first episode, short duration (<1 year) and drug-naïve depression patients, and 25 healthy control (HC) subjects were recruited. To construct the WM structural network, atlas-based brain regions were used for nodes, and the value of multiplying fiber number by the mean fractional anisotropy along the fiber bundles connected a pair of brain regions were used for edges. The structural network was analyzed by graph theoretic and network-based statistic methods. Pearson partial correlation analysis was also performed to evaluate their correlation with the clinical variables. Compared with HCs, the MDD patients had a significant decrease in the small-worldness (σ). Meanwhile, the MDD patients presented a significantly decreased subnetwork, which mainly involved in the frontal-subcortical and limbic regions. Our results suggested that the abnormal structural network of the orbitofrontal cortex and thalamus, involving the imbalance with the limbic system, might be a key pathology in early stage drug-naive depression. And the structural network analysis might be potential in early detection and diagnosis of MDD.

Alternations of White Matter Structural Networks in First Episode Untreated Major Depressive Disorder with Short Duration

PubMed Central

Lu, Yi; Shen, Zonglin; Cheng, Yuqi; Yang, Hui; He, Bo; Xie, Yue; Wen, Liang; Zhang, Zhenguang; Sun, Xuejin; Zhao, Wei; Xu, Xiufeng; Han, Dan

2017-01-01

It is crucial to explore the pathogenesis of major depressive disorder (MDD) at the early stage for the better diagnostic and treatment strategies. It was suggested that MDD might be involving in functional or structural alternations at the brain network level. However, at the onset of MDD, whether the whole brain white matter (WM) alterations at network level are already evident still remains unclear. In the present study, diffusion MRI scanning was adopt to depict the unique WM structural network topology across the entire brain at the early stage of MDD. Twenty-one first episode, short duration (<1 year) and drug-naïve depression patients, and 25 healthy control (HC) subjects were recruited. To construct the WM structural network, atlas-based brain regions were used for nodes, and the value of multiplying fiber number by the mean fractional anisotropy along the fiber bundles connected a pair of brain regions were used for edges. The structural network was analyzed by graph theoretic and network-based statistic methods. Pearson partial correlation analysis was also performed to evaluate their correlation with the clinical variables. Compared with HCs, the MDD patients had a significant decrease in the small-worldness (σ). Meanwhile, the MDD patients presented a significantly decreased subnetwork, which mainly involved in the frontal–subcortical and limbic regions. Our results suggested that the abnormal structural network of the orbitofrontal cortex and thalamus, involving the imbalance with the limbic system, might be a key pathology in early stage drug-naive depression. And the structural network analysis might be potential in early detection and diagnosis of MDD. PMID:29118724

Differences in graph theory functional connectivity in left and right temporal lobe epilepsy.

PubMed

Chiang, Sharon; Stern, John M; Engel, Jerome; Levin, Harvey S; Haneef, Zulfi

2014-12-01

To investigate lateralized differences in limbic system functional connectivity between left and right temporal lobe epilepsy (TLE) using graph theory. Interictal resting state fMRI was performed in 14 left TLE patients, 11 right TLE patients, and 12 controls. Graph theory analysis of 10 bilateral limbic regions of interest was conducted. Changes in edgewise functional connectivity, network topology, and regional topology were quantified, and then left and right TLE were compared. Limbic edgewise functional connectivity was predominantly reduced in both left and right TLE. More regional connections were reduced in right TLE, most prominently involving reduced interhemispheric connectivity between the bilateral insula and bilateral hippocampi. A smaller number of limbic connections were increased in TLE, more so in left than in right TLE. Topologically, the most pronounced change was a reduction in average network betweenness centrality and concurrent increase in left hippocampal betweenness centrality in right TLE. In contrast, left TLE exhibited a weak trend toward increased right hippocampal betweenness centrality, with no change in average network betweenness centrality. Limbic functional connectivity is predominantly reduced in both left and right TLE, with more pronounced reductions in right TLE. In contrast, left TLE exhibits both edgewise and topological changes that suggest a tendency toward reorganization. Network changes in TLE and lateralized differences thereof may have important diagnostic and prognostic implications. Published by Elsevier B.V.

Functional neuroimaging of emotional processing in women with polycystic ovary syndrome: a case-control pilot study

PubMed Central

Marsh, Courtney A.; Berent-Spillson, Alison; Love, Tiffany; Persad, Carol C.; Pop-Busui, Rodica; Zubieta, Jon-Kar; Smith, Yolanda R.

2013-01-01

Objective To evaluate emotional processing in women with insulin-resistant polycystic ovary syndrome (IR-PCOS) and its relationship to glucose regulation and the mu-opioid system. Design Case-control pilot. Setting Tertiary referring medical center. Patient(s) Seven women with IR-PCOS and five non-insulin-resistant controls, aged 21–40 years, recruited from the general population. Intervention(s) Sixteen weeks of metformin (1,500 mg/day) in women with IR-PCOS. Main Outcome Measure(s) Assessment of mood, metabolic function, and neuronal activation during an emotional task using functional magnetic resonance imaging (fMRI), and mu-opioid receptor availability using positive emission tomography (PET). Result(s) We found that insulin-resistant PCOS patients [1] had greater limbic activation during an emotion task than controls (n = 5); [2] trended toward decreased positive affect and increased trait anxiety; [3] after metformin treatment, had limbic activation that no longer differed from controls; and [4] had positive correlations between fMRI limbic activation during emotional processing and mu-opioid binding potential. Conclusion(s) Patients with IR-PCOS had greater regional activation during an emotion task than the controls, although this resolved with metformin therapy. Alterations in mu-opioid neurotransmission may underlie limbic system activity and mood disorders in IR-PCOS. Clinical Trial Registration Number NCT00670800. PMID:23557757

Common modulation of limbic network activation underlies musical emotions as they unfold.

PubMed

Singer, Neomi; Jacoby, Nori; Lin, Tamar; Raz, Gal; Shpigelman, Lavi; Gilam, Gadi; Granot, Roni Y; Hendler, Talma

2016-11-01

Music is a powerful means for communicating emotions among individuals. Here we reveal that this continuous stream of affective information is commonly represented in the brains of different listeners and that particular musical attributes mediate this link. We examined participants' brain responses to two naturalistic musical pieces using functional Magnetic Resonance imaging (fMRI). Following scanning, as participants listened to the musical pieces for a second time, they continuously indicated their emotional experience on scales of valence and arousal. These continuous reports were used along with a detailed annotation of the musical features, to predict a novel index of Dynamic Common Activation (DCA) derived from ten large-scale data-driven functional networks. We found an association between the unfolding music-induced emotionality and the DCA modulation within a vast network of limbic regions. The limbic-DCA modulation further corresponded with continuous changes in two temporal musical features: beat-strength and tempo. Remarkably, this "collective limbic sensitivity" to temporal features was found to mediate the link between limbic-DCA and the reported emotionality. An additional association with the emotional experience was found in a left fronto-parietal network, but only among a sub-group of participants with a high level of musical experience (>5years). These findings may indicate two processing-levels underlying the unfolding of common music emotionality; (1) a widely shared core-affective process that is confined to a limbic network and mediated by temporal regularities in music and (2) an experience based process that is rooted in a left fronto-parietal network that may involve functioning of the 'mirror-neuron system'. Copyright © 2016 Elsevier Inc. All rights reserved.

Neural mechanisms of genetic risk for impulsivity and violence in humans.

PubMed

Meyer-Lindenberg, Andreas; Buckholtz, Joshua W; Kolachana, Bhaskar; R Hariri, Ahmad; Pezawas, Lukas; Blasi, Giuseppe; Wabnitz, Ashley; Honea, Robyn; Verchinski, Beth; Callicott, Joseph H; Egan, Michael; Mattay, Venkata; Weinberger, Daniel R

2006-04-18

Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functional polymorphism in MAOA on brain structure and function assessed with MRI in a large sample of healthy human volunteers. We show that the low expression variant, associated with increased risk of violent behavior, predicted pronounced limbic volume reductions and hyperresponsive amygdala during emotional arousal, with diminished reactivity of regulatory prefrontal regions, compared with the high expression allele. In men, the low expression allele is also associated with changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during aversive recall, and impaired cingulate activation during cognitive inhibition. Our data identify differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression, suggest neural systems-level effects of X-inactivation in human brain, and point toward potential targets for a biological approach toward violence.

Neural signatures of cognitive and emotional biases in depression

PubMed Central

Fossati, Philippe

2008-01-01

Functional brain imaging studies suggest that depression is a system-level disorder affecting discrete but functionally linked cortical and limbic structures, with abnormalities in the anterior cingulate, lateral, ami medial prefrontal cortex, amygdala, ami hippocampus. Within this circuitry, abnormal corticolimbic interactions underlie cognitive deficits ami emotional impairment in depression. Depression involves biases toward processing negative emotional information and abnormal self-focus in response to emotional stimuli. These biases in depression could reflect excessive analytical self-focus in depression, as well as impaired cognitive control of emotional response to negative stimuli. By combining structural and functional investigations, brain imaging studies mav help to generate novel antidepressant treatments that regulate structural and factional plasticity within the neural network regulating mood and affective behavior.

Limbic encephalitis associated with systemic lupus erythematosus.

PubMed

Kano, O; Arasaki, K; Ikeda, K; Aoyagi, J; Shiraishi, H; Motomura, M; Iwasaki, Y

2009-12-01

A 34-year-old woman with systemic lupus erythematosus (SLE) presented with general fatigue, seizures and memory loss. Magnetic resonance imaging of the brain showed a high signal area in the mesial temporal lobe bilaterally. Computed tomography scan of the chest and abdomen and ultrasound of pelvis detected no malignancy and tumour marker, antibodies to antineuronal antibodies (anti-Hu, anti-Ta and anti-Ma) and antibodies to voltage-gated potassium channels were all negative. The present case is limbic encephalitis (LE) associated with SLE and the pathogenesis may include autoimmunity shared. Our experience indicates that the immunologic spectrum of LE will expand to include additional immune mechanisms.

FNDC5/irisin, a molecular target for boosting reward-related learning and motivation.

PubMed

Zsuga, Judit; Tajti, Gabor; Papp, Csaba; Juhasz, Bela; Gesztelyi, Rudolf

2016-05-01

Interventions focusing on the prevention and treatment of chronic non-communicable diseases are on rise. In the current article, we propose that dysfunction of the mesocortico-limbic reward system contributes to the emergence of the WHO-identified risk behaviors (tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol), behaviors that underlie the evolution of major non-communicable diseases (e.g. cardiovascular diseases, cancer, diabetes and chronic respiratory diseases). Given that dopaminergic neurons of the mesocortico-limbic system are tightly associated with reward-related processes and motivation, their dysfunction may fundamentally influence behavior. While nicotine and alcohol alter dopamine neuron function by influencing some receptors, mesocortico-limbic system dysfunction was associated with elevation of metabolic set-point leading to hedonic over-eating. Although there is some empirical evidence, precise molecular mechanism for linking physical inactivity and mesocortico-limbic dysfunction per se seems to be missing; identification of which may contribute to higher success rates for interventions targeting lifestyle changes pertaining to physical activity. In the current article, we compile evidence in support of a link between exercise and the mesocortico-limbic system by elucidating interactions on the axis of muscle - irisin - brain derived neurotrophic factor (BDNF) - and dopaminergic function of the midbrain. Irisin is a contraction-regulated myokine formed primarily in skeletal muscle but also in the brain. Irisin stirred considerable interest, when its ability to induce browning of white adipose tissue parallel to increasing thermogenesis was discovered. Furthermore, it may also play a role in the regulation of behavior given it readily enters the central nervous system, where it induces BDNF expression in several brain areas linked to reward processing, e.g. the ventral tegmental area and the hippocampus. BDNF is a neurotropic factor that increases neuronal dopamine content, modulates dopamine release relevant for neuronal plasticity and increased neuronal survival as well as learning and memory. Further linking BDNF to dopaminergic function is BDNF's ability to activate tropomyosin-related kinase B receptor that shares signalization with presynaptic dopamine-3 receptors in the ventral tegmental area. Summarizing, we propose that the skeletal muscle derived irisin may be the link between physical activity and reward-related processes and motivation. Moreover alteration of this axis may contribute to sedentary lifestyle and subsequent non-communicable diseases. Preclinical and clinical experimental models to test this hypothesis are also proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Psychotherapy of Depression as Neurobiological Process - Evidence from Neuroimaging].

PubMed

Rubart, Antonie; Hohagen, Fritz; Zurowski, Bartosz

2018-06-01

Research on neurobiological effects of psychotherapy in depression facilitates the improvement of treatment strategies. The cortico-limbic dysregulation model serves as a framework for numerous studies on neurobiological changes in depression. In this model, depression is described as hypoactivation of dorsal cortical brain regions in conjunction with hyperactivation of ventral paralimbic regions. This assumption has been supported by various studies of structural and functional brain abnormalities in depression. However, also regions not included in the original cortico-limbic dysregulation model, such as the dorsomedial prefrontal cortex, seem to play an important role in depression. Functional connectivity studies of depression have revealed an enhanced connectivity within the so-called default mode network which is involved in self-referential thinking. Studies also point to a normalization of limbic and cortical brain activity, especially in the anterior cingulate cortex, during psychotherapy. Some neurobiological markers like the activity of the anterior cingulate cortex, striatum and insula as well as hippocampal volume have been proposed to predict treatment response on a group-level. The activity of the anterior insula appears to be a candidate bio-marker for differential indication for psychotherapy or pharmacotherapy. The cortico-limbic dysregulation model and following research have inspired new forms of treatment for depression like deep brain stimulation of the subgenual anterior cingulate cortex, repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex, neurofeedback and attention training. © Georg Thieme Verlag KG Stuttgart · New York.

Atrial Fibrillation: The Science behind Its Defiance

PubMed Central

Czick, Maureen E.; Shapter, Christine L.; Silverman, David I.

2016-01-01

Atrial fibrillation (AF) is the most prevalent arrhythmia in the world, due both to its tenacious treatment resistance, and to the tremendous number of risk factors that set the stage for the atria to fibrillate. Cardiopulmonary, behavioral, and psychological risk factors generate electrical and structural alterations of the atria that promote reentry and wavebreak. These culminate in fibrillation once atrial ectopic beats set the arrhythmia process in motion. There is growing evidence that chronic stress can physically alter the emotion centers of the limbic system, changing their input to the hypothalamic-limbic-autonomic network that regulates autonomic outflow. This leads to imbalance of the parasympathetic and sympathetic nervous systems, most often in favor of sympathetic overactivation. Autonomic imbalance acts as a driving force behind the atrial ectopy and reentry that promote AF. Careful study of AF pathophysiology can illuminate the means that enable AF to elude both pharmacological control and surgical cure, by revealing ways in which antiarrhythmic drugs and surgical and ablation procedures may paradoxically promote fibrillation. Understanding AF pathophysiology can also help clarify the mechanisms by which emerging modalities aiming to correct autonomic imbalance, such as renal sympathetic denervation, may offer potential to better control this arrhythmia. Finally, growing evidence supports lifestyle modification approaches as adjuncts to improve AF control. PMID:27699086

The neuropsychology of development hemispheric laterality, limbic language, and the origin of thought.

PubMed

Joseph, R

1982-01-01

Discussed evidence and assumptions that concern hemispheric laterality and asymmetrical functional representation. It is hypothesized that the asymmetrical linguistic-motor vs. sensory-spatial-affective representation of function may be a result of differential rates of cortical, subcortical and spinal motor-sensory maturation. Evidence with regard to embryological and early postnatal neurological development is reviewed. It is argued that motor areas mature before sensory and that the left hemisphere develops prior to the right, such that the left hemisphere gains a competitive advantage in the acquisition of motor representation, whereas the later maturing right has an advantage in the establishment of sensory-affective synaptic representation, including that of limbic mediation. The influences of these differing maturational events on cognitive and psychic functioning are examined, particularly with regard to limbic influences on the development of language, thought, and mental imagery, and the effects of early emotional experience on later behavior. Thinking is viewed in part as a left hemisphere internalization of egocentric language, the internalization of which corresponds to the increasing maturation of intra-cortical and subcortical structures and fiber pathways, and the myelination of the callosal connections that subserve information transfer between the hemispheres. It is argued that thought is a means of organizing, interpreting, and explaining impulses that arise in the non-linguistic portions of the nervous system so that the language dependent regions may achieve understanding. In addition, the neurodynamics and mechanisms involved in the mislabeling, misinterpretation, and inhibition of impulses, desires, and emotional expression are discussed in relation to disturbances in psychic functioning.

On whether mirror neurons play a significant role in processing affective prosody.

PubMed

Ramachandra, Vijayachandra

2009-02-01

Several behavioral and neuroimaging studies have indicated that both right and left cortical structures and a few subcortical ones are involved in processing affective prosody. Recent investigations have shown that the mirror neuron system plays a crucial role in several higher-level functions such as empathy, theory of mind, language, etc., but no studies so far link the mirror neuron system with affective prosody. In this paper is a speculation that the mirror neuron system, which serves as a common neural substrate for different higher-level functions, may play a significant role in processing affective prosody via its connections with the limbic lobe. Actual research must apply electrophysiological and neuroimaging techniques to assess whether the mirror neuron systems underly affective prosody in humans.

Reduced Amygdalar Gray Matter Volume in Familial Pediatric Bipolar Disorder

ERIC Educational Resources Information Center

Chang, Kiki; Karchemskiy, Asya; Barnea-Goraly, Naama; Garrett, Amy; Simeonova, Diana Iorgova; Reiss, Allan

2005-01-01

Objective: Subcortical limbic structures have been proposed to be involved in the pathophysiology of adult and pediatric bipolar disorder (BD). We sought to study morphometric characteristics of these structures in pediatric subjects with familial BD compared with healthy controls. Method: Twenty children and adolescents with BD I (mean age = 14.6…

Autobiographical memory in semantic dementia: implication for theories of limbic-neocortical interaction in remote memory.

PubMed

McKinnon, Margaret C; Black, Sandra E; Miller, Bruce; Moscovitch, Morris; Levine, Brian

2006-01-01

We examined autobiographical memory performance in two patients with semantic dementia using a novel measure, the Autobiographical Interview [Levine, Svoboda, Hay, Winocur, & Moscovitch (2002). Aging and autobiographical memory: Dissociating episodic from semantic retrieval. Psychology and Aging, 17, 677-689], that is capable of dissociating episodic and personal semantic recall under varying levels of retrieval support. Earlier reports indicated that patients with semantic dementia demonstrate autobiographical episodic memory loss following a "reverse gradient" by which recent memories are preserved relative to remote memories. We found limited evidence for this pattern at conditions of low retrieval support. When structured probing was provided, patients' autobiographical memory performance was similar to that of controls. Retesting of one patient after 1 year indicated that retrieval support was insufficient to bolster performance following progressive prefrontal volume loss, as documented with quantified structural neuroimaging. These findings are discussed in relation to theories of limbic-neocortical interaction in autobiographical memory.

Examining the effect of psychopathic traits on gray matter volume in a community substance abuse sample.

PubMed

Cope, Lora M; Shane, Matthew S; Segall, Judith M; Nyalakanti, Prashanth K; Stevens, Michael C; Pearlson, Godfrey D; Calhoun, Vince D; Kiehl, Kent A

2012-11-30

Psychopathy is believed to be associated with brain abnormalities in both paralimbic (i.e., orbitofrontal cortex, insula, temporal pole, parahippocampal gyrus, posterior cingulate) and limbic (i.e., amygdala, hippocampus, anterior cingulate) regions. Recent structural imaging studies in both community and prison samples are beginning to support this view. Sixty-six participants, recruited from community corrections centers, were administered the Hare psychopathy checklist-revised (PCL-R), and underwent magnetic resonance imaging (MRI). Voxel-based morphometry was used to test the hypothesis that psychopathic traits would be associated with gray matter reductions in limbic and paralimbic regions. Effects of lifetime drug and alcohol use on gray matter volume were covaried. Psychopathic traits were negatively associated with gray matter volumes in right insula and right hippocampus. Additionally, psychopathic traits were positively associated with gray matter volumes in bilateral orbital frontal cortex and right anterior cingulate. Exploratory regression analyses indicated that gray matter volumes within right hippocampus and left orbital frontal cortex combined to explain 21.8% of the variance in psychopathy scores. These results support the notion that psychopathic traits are associated with abnormal limbic and paralimbic gray matter volume. Furthermore, gray matter increases in areas shown to be functionally impaired suggest that the structure-function relationship may be more nuanced than previously thought. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Area 4 has layer IV in adult primates

PubMed Central

García-Cabezas, Miguel Ángel; Barbas, Helen

2014-01-01

There are opposing views about the status of layer IV in primary motor cortex (area 4). Cajal described a layer IV in area 4 of adult humans. In contrast, Brodmann found layer IV in development but not in adult primates and called area 4 ‘agranular’. We addressed this issue in rhesus monkeys using the neural marker SMI-32, which labels neurons in lower layer III and upper V, but not in layer IV. SMI-32 delineated a central unlabeled cortical stripe in area 4 that corresponds to layer IV, which was populated with small interneurons also found in layer IV in ‘granular’ areas (such as area 46). We distinguished layer IV interneurons from projection neurons in the layers above and below using cellular criteria. The commonly used term ‘agranular’ for area 4 is also used for the phylogenetically ancient limbic cortices, confusing areas that differ markedly in laminar structure. This issue pertains to the systematic variation in the architecture across cortices, traced from limbic cortices through areas with increasingly more elaborate laminar structure. The principle of systematic variation can be used to predict laminar patterns of connections across cortical systems. This principle places area 4 and agranular anterior cingulate cortices at opposite poles of the graded laminar differentiation of motor cortices. The status of layer IV in area 4 thus pertains to core organizational features of the cortex, its connections and evolution. PMID:24735460

Chronic stress disrupts neural coherence between cortico-limbic structures.

PubMed

Oliveira, João Filipe; Dias, Nuno Sérgio; Correia, Mariana; Gama-Pereira, Filipa; Sardinha, Vanessa Morais; Lima, Ana; Oliveira, Ana Filipa; Jacinto, Luís Ricardo; Ferreira, Daniela Silva; Silva, Ana Maria; Reis, Joana Santos; Cerqueira, João José; Sousa, Nuno

2013-01-01

Chronic stress impairs cognitive function, namely on tasks that rely on the integrity of cortico-limbic networks. To unravel the functional impact of progressive stress in cortico-limbic networks we measured neural activity and spectral coherences between the ventral hippocampus (vHIP) and the medial prefrontal cortex (mPFC) in rats subjected to short term stress (STS) and chronic unpredictable stress (CUS). CUS exposure consistently disrupted the spectral coherence between both areas for a wide range of frequencies, whereas STS exposure failed to trigger such effect. The chronic stress-induced coherence decrease correlated inversely with the vHIP power spectrum, but not with the mPFC power spectrum, which supports the view that hippocampal dysfunction is the primary event after stress exposure. Importantly, we additionally show that the variations in vHIP-to-mPFC coherence and power spectrum in the vHIP correlated with stress-induced behavioral deficits in a spatial reference memory task. Altogether, these findings result in an innovative readout to measure, and follow, the functional events that underlie the stress-induced reference memory impairments.

Autoimmune Limbic Encephalitis and Syndrome of Inappropriate Antidiuretic Hormone Secretion Associated with Lamotrigine-induced Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) Syndrome.

PubMed

Ozisik, Lale; Tanriover, Mine Durusu; Saka, Esen

2016-01-01

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug hypersensitivity reaction characterized by rash, fever and multi-organ failure. Limbic encephalitis (LE) is a rare disorder characterized by cognitive dysfunction with memory disturbance, seizures and psychiatric symptoms. We herein present an unusual case of DRESS syndrome due to lamotrigine with reactivation of Epstein-Barr virus, which developed autoimmune LE and syndrome of inappropriate antidiuretic hormone secretion. Discontinuation of lamotrigine, administration of methylprednisolone and intravenous immunoglobulin led to improvement. The LE in this case might have been caused by an autoimmune inflammatory mechanism associated with DRESS syndrome.

Two different mirror neuron networks: The sensorimotor (hand) and limbic (face) pathways.

PubMed

Ferrari, P F; Gerbella, M; Coudé, G; Rozzi, S

2017-09-01

The vast majority of functional studies investigating mirror neurons (MNs) explored their properties in relation to hand actions, and very few investigated how MNs respond to mouth actions or communicative gestures. Since hand and mouth MNs were recorded in two partially overlapping sectors of the ventral precentral cortex of the macaque monkey, there is a general assumption that they share a same neuroanatomical network, with the parietal cortex as a main source of visual information. In the current review, we challenge this perspective and describe the connectivity pattern of mouth MN sector. The mouth MNs F5/opercular region is connected with premotor, parietal areas mostly related to the somatosensory and motor representation of the face/mouth, and with area PrCO, involved in processing gustatory and somatosensory intraoral input. Unlike hand MNs, mouth MNs do not receive their visual input from parietal regions. Such information related to face/communicative behaviors could come from the ventrolateral prefrontal cortex. Further strong connections derive from limbic structures involved in encoding emotional facial expressions and motivational/reward processing. These brain structures include the anterior cingulate cortex, the anterior and mid-dorsal insula, orbitofrontal cortex and the basolateral amygdala. The mirror mechanism is therefore composed and supported by at least two different anatomical pathways: one is concerned with sensorimotor transformation in relation to reaching and hand grasping within the traditional parietal-premotor circuits; the second one is linked to the mouth/face motor control and is connected with limbic structures, involved in communication/emotions and reward processing. Copyright © 2017. Published by Elsevier Ltd.

[Intensity of pentose phosphate metabolism of carbohydrates in various brain areas in normal and starved animals].

PubMed

Kerimov, B F

2002-01-01

The activities of key enzymes of pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G-6 PD) and 6-phosphogluconate dehydrogenase (6-PGD), were studied in cytoplasmatic fractions of brain cortical (limbic, orbital, sensorimotor cortex) and subcortical (myelencefalon, mesencefalon, hypothalamus) structures of rats subjected to starvation for 1, 2, 3, 5 and 7 days. Short-term starvation (1-3 days) caused activation of 6-GPD and 6-PGD both in cortical and subcortical structures. Long-term starvation for 5-7 days caused a decrease of activities of the pentose phosphate pathway enzymes in all studied structures. It is suggested that enzymes of pentose phosphate pathway in nervous tissues are functionally and metabolically related to glutathione system and during starvation they indirectly participate in the regulation lipid peroxidation processes.

The semiology of febrile seizures: Focal features are frequent.

PubMed

Takasu, Michihiko; Kubota, Tetsuo; Tsuji, Takeshi; Kurahashi, Hirokazu; Numoto, Shingo; Watanabe, Kazuyoshi; Okumura, Akihisa

2017-08-01

To clarify the semiology of febrile seizures (FS) and to determine the frequency of FS with symptoms suggestive of focal onset. FS symptoms in children were reported within 24h of seizure onset by the parents using a structured questionnaire consisting principally of closed-ended questions. We focused on events at seizure commencement, including changes in behavior and facial expression, and ocular and oral symptoms. We also investigated the autonomic and motor symptoms developing during seizures. The presence or absence of focal and limbic features was determined for each patient. The associations of certain focal and limbic features with patient characteristics were assessed. Information was obtained on FS in 106 children. Various events were recorded at seizure commencement. Behavioral changes were observed in 35 children, changes in facial expression in 53, ocular symptoms in 78, and oral symptoms in 90. In terms of events during seizures, autonomic symptoms were recognized in 78, and convulsive motor symptoms were recognized in 68 children. Focal features were evident in 81 children; 38 children had two or more such features. Limbic features were observed in 44 children, 9 of whom had two or more such features. There was no significant relationship between any patient characteristic and the numbers of focal or limbic features. The semiology of FS varied widely among children, and symptoms suggestive of focal onset were frequent. FS of focal onset may be more common than is generally thought. Copyright © 2017 Elsevier Inc. All rights reserved.

Distinct white matter integrity in glutamic acid decarboxylase and voltage-gated potassium channel-complex antibody-associated limbic encephalitis.

PubMed

Wagner, Jan; Schoene-Bake, Jan-Christoph; Witt, Juri-Alexander; Helmstaedter, Christoph; Malter, Michael P; Stoecker, Winfried; Probst, Christian; Weber, Bernd; Elger, Christian E

2016-03-01

Autoantibodies against glutamic acid decarboxylase (GAD) and the voltage-gated potassium channel (VGKC) complex are associated with distinct subtypes of limbic encephalitis regarding clinical presentation, response to therapy, and outcome. The aim of this study was to investigate white matter changes in these two limbic encephalitis subtypes by means of diffusion tensor imaging (DTI). Diffusion data were obtained in 14 patients with GAD antibodies and 16 patients with VGKC-complex antibodies and compared with age- and gender-matched control groups. Voxelwise statistical analysis was carried out using tract-based spatial statistics. The results were furthermore compared with those of 15 patients with unilateral histologically confirmed hippocampal sclerosis and correlated with verbal and figural memory performance. We found widespread changes of fractional anisotropy and all diffusivity parameters in GAD-associated limbic encephalitis, whereas no changes were found in VGKC-complex-associated limbic encephalitis. The changes observed in the GAD group were even more extensive when compared against those of the hippocampal sclerosis group, although the disease duration was markedly shorter in patients with GAD antibodies. Correlation analysis revealed areas with a trend toward a negative correlation of diffusivity parameters with figural memory performance located mainly in the right temporal lobe in the GAD group as well. The present study provides further evidence that, depending on the associated antibody, limbic encephalitis features clearly distinct imaging characteristics by showing widespread white matter changes in GAD-associated limbic encephalitis and preserved white matter integrity in VGKC-complex-associated limbic encephalitis. Furthermore, our results contribute to a better understanding of the specific pathophysiologic properties in these two subforms of limbic encephalitis by revealing that patients with GAD antibodies show widespread affections of white matter across various regions of the brain. In contrast to this, the inflammatory process seems to be more localized in VGKC-complex-associated limbic encephalitis, primarily affecting mesiotemporal gray matter. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

The effects of a virtual reality treatment program for online gaming addiction.

PubMed

Park, Sung Yong; Kim, Sun Mi; Roh, Sungwon; Soh, Min-Ah; Lee, Sang Hoon; Kim, Hyungjin; Lee, Young Sik; Han, Doug Hyun

2016-06-01

Neuroimaging studies have demonstrated dysfunction in the brain reward circuit in individuals with online gaming addiction (OGA). We hypothesized that virtual reality therapy (VRT) for OGA would improve the functional connectivity (FC) of the cortico-striatal-limbic circuit by stimulating the limbic system. Twenty-four adults with OGA were randomly assigned to a cognitive behavior therapy (CBT) group or VRT group. Before and after the four-week treatment period, the severity of OGA was evaluated with Young's Internet Addiction Scale (YIAS). Using functional magnetic resonance imaging, the amplitude of low-frequency fluctuation (ALFF) and FC from the posterior cingulate cortex (PCC) seed to other brain areas were evaluated. Twelve casual game users were also recruited and underwent only baseline assessment. After treatment, both CBT and VRT groups showed reductions in YIAS scores. At baseline, the OGA group showed a smaller ALFF within the right middle frontal gyrus and reduced FC in the cortico-striatal-limbic circuit. In the VRT group, connectivity from the PCC seed to the left middle frontal and bilateral temporal lobe increased after VRT. VRT seemed to reduce the severity of OGA, showing effects similar to CBT, and enhanced the balance of the cortico-striatal-limbic circuit. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The glass ceiling: A biological phenomenon.

PubMed

Schulpen, Tom W J

2017-09-01

Many brilliant and ambitious young women lose their drive for top careers after childbirth. New maternal impulses are at odds with their original ambitions and for many mothers stress and frustration will be the result as they have to combine child care with workweeks of 60-80h to reach or remain at the top. Pregnancy hormones modify the female's brain as has been demonstrated already for decades in animals. This brain plasticity due to adult neurogenesis in the so called maternal circuitry of the limbic system is long-lasting and perhaps lifelong. In humans hormonal and neuro-imaging studies show ample evidence for fundamental and long lasting pregnancy induced brain changes, not only in the limbic system, but also in the cortical networks like theory of mind and mirror neuron system. Recent research shows pronounced and long lasting brain changes in several of these areas. It can be concluded that there exists a maternal brain that drives mother's behaviour and priorities. Research in men shows that the more fathers are involved in raising their children, the more caring behaviour they develop. Structural anatomical changes are found in neural regions involved in parental motivation. These studies show that brain plasticity in fathers is experience dependent. In Nordic countries, a policy of paid paternal leave followed by a flexible shared parental leave, stimulates fatherly behaviour. This might reduce men's eagerness for top careers, thus creating better opportunities for women. Demolition of women's glass ceiling starts with the father. Copyright © 2017 Elsevier Ltd. All rights reserved.

Revealing the cerebello-ponto-hypothalamic pathway in the human brain.

PubMed

Kamali, Arash; Karbasian, Niloofar; Rabiei, Pejman; Cano, Andres; Riascos, Roy F; Tandon, Nitin; Arevalo, Octavio; Ocasio, Laura; Younes, Kyan; Khayat-Khoei, Mahsa; Mirbagheri, Saeedeh; Hasan, Khader M

2018-06-11

The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. Copyright © 2018 Elsevier B.V. All rights reserved.

A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system

PubMed Central

Lopes, M W; Leal, R B; Guarnieri, R; Schwarzbold, M L; Hoeller, A; Diaz, A P; Boos, G L; Lin, K; Linhares, M N; Nunes, J C; Quevedo, J; Bortolotto, Z A; Markowitsch, H J; Lightman, S L; Walz, R

2016-01-01

Glucocorticoids (GC) released during stress response exert feedforward effects in the whole brain, but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC are the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events. Through a quasi-randomized controlled study, we show that a single high dexamethasone dose significantly reduces in a dose-dependent manner the levels of GluA1-Ser831 phosphorylation in the amygdala resected during surgery for temporal lobe epilepsy. This is the first report demonstrating GC effects on key markers of synaptic neuroplasticity in the human limbic system. The results contribute to understanding how GC affects the human brain under physiologic and pharmacologic conditions. PMID:27959333

[The neurobiology of antisocial behaviour].

PubMed

Loomans, M M; Tulen, J H M; van Marle, H J C

2010-01-01

Neuro-imaging is being used increasingly to provide explanations for antisocial behaviour. To make a neurobiological contribution to the diagnosis of many types of antisocial behaviour. The literature was searched using PubMed and combinations of the keywords 'psychopathy', 'antisocial', 'neurobiology' and 'neuro-anatomy' for the period 1990-2009. Impairments in the prefrontal cortex, amygdala, hippocampus, superior temporal gyrus, corpus callosum and anterior cingulate cortex provide a possible explanation for a large number of the symptoms associated with antisocial behaviour. The concept of psychopathy is connected mainly with impairments in a prefrontal-temporal-limbic system. CONCLUSION Combinations of deficiencies in the associated brain areas and malfunctioning of the communication between the various brain structures seem to play a more important role than deficiencies in the separate brain structures.

Hypothalamic tumors impact gray and white matter volumes in fronto-limbic brain areas.

PubMed

Özyurt, Jale; Müller, Hermann L; Warmuth-Metz, Monika; Thiel, Christiane M

2017-04-01

Patients with hypothalamic involvement of a sellar/parasellar tumor often suffer from cognitive and social-emotional deficits that a lesion in the hypothalamus cannot fully explain. It is conceivable that these deficits are partly due to distal changes in hypothalamic networks, evolving secondary to a focal lesion. Focusing on childhood-onset craniopharyngioma patients, we aimed at investigating the impact of hypothalamic lesions on gray and white matter areas densely connected to the hypothalamus, and to relate structural changes to neuropsychological deficits frequently observed in patients. We performed a voxel-based morphometric analysis based on data of 11 childhood-onset craniopharyngioma patients with hypothalamic tumor involvement, and 18 healthy controls (median age: 17.2 and 17.4 yrs.). Whole-brain analyses were used to test for volumetric differences between the groups (T-tests) and subsequent regression analyses were used to correlate neuropsychological performance with gray and white matter volumes within the patient group. Patients compared to controls had significantly reduced gray matter volumes in areas of the anterior and posterior limbic subsystems which are densely connected with the hypothalamus. In addition, a reduction in white matter volumes was observed in tracts connecting the hypothalamus to other limbic areas. Worse long-term memory retrieval was correlated with smaller gray matter volumes in the posterior cingulate cortex. Our data provide the first evidence that hypothalamic tumor involvement impacts gray and white matter volumes in limbic areas, outside the area of tumor growth. Notably, the functional range of the two limbic subsystems affected, strikingly parallels the two major domains of psychological complaints in patients i.e., deficits in episodic memory and in socio-emotional functioning. We suggest that focal hypothalamic lesions may trigger distal changes in connected brain areas, which then contribute to the impairments in cognitive, social and emotional performance often observable in patients, and not explicable by a hypothalamic lesion alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuroticism is linked to microstructural left-right asymmetry of fronto-limbic fibre tracts in adolescents with opposite effects in boys and girls.

PubMed

Madsen, Kathrine Skak; Jernigan, Terry L; Vestergaard, Martin; Mortensen, Erik Lykke; Baaré, William F C

2018-06-01

Neuroticism is a fundamental personality trait that reflects a tendency to experience heightened negative affect and susceptibility to stress. Negative emotionality has been associated with fronto-limbic brain structures and connecting fibre tracts. The major fibre tracts connecting the frontal and limbic brain regions are the cingulum bundle and uncinate fasciculus. We previously found that healthy adults with higher neuroticism scores had decreased left relative to right fractional anisotropy (FA) of the cingulum. Both cingulum and uncinate fasciculus FA increases throughout childhood and into early adulthood. Since adolescence is associated with an increased incidence of anxiety and mood disorders, for which neuroticism is a known risk factor, the question arises whether the association between neuroticism and fronto-limbic white matter microstructure asymmetry is already present in children and adolescents or whether such relationship emerges during this age period. To address this question, we assessed 72 typically-developing 10-to-15 year-olds with diffusion-weighted imaging on a 3 T magnetic resonance scanner. Neuroticism was assessed with the Junior Eysenck Personality Questionnaire. FA and parallel and perpendicular diffusivity measures were extracted for cingulum, uncinate fasciculus as well as the white matter underlying the ventromedial prefrontal cortex. Higher neuroticism scores were associated with decreased left relative to right cingulum FA in boys, while in girls, higher neuroticism scores were associated with increased left relative to right cingulum and ventromedial prefrontal white matter FA, indicating that there are sex differences in the neural correlates of neuroticism. Our findings suggest that the link between neuroticism and frontal-limbic white matter microstructure asymmetry likely predates early adolescence. Future studies need to elucidate the significance of the observed sex differences in the neural correlates of neuroticism. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Opioid neurotoxicity: neuropathologic effects in rats of different fentanyl congeners and the effects of hexamethonium-induced normotension.

PubMed

Kofke, W A; Garman, R H; Janosky, J; Rose, M E

1996-07-01

We tested the hypotheses that convulsant doses of opioids would produce limbic system damage exacerbated by hexamethonium. Ventilated paralyzed rats received intravenous (IV) isovolumic infusion of fentanyl loading dose (LD) 1000 micrograms/kg, maintenance dose (MD) 40 micrograms.kg-1.min-1 (n = 10), sufentanil LD 400 micrograms/kg, MD 13.3 micrograms.kg-1.min-1 (n = 10), alfentanil LD 1500 micrograms/kg, MD 150 micrograms.kg-1.min-1 (n = 10), or 0.9% saline control LD 4 mliter/kg, MD 4 mliter.kg-1.h-1 (n = 10), with O2/N2 30%/70% during opioid infusion and O2/N2O in controls during saline infusion. Hexamethonium (LD 20 mg/kg, MD 40-120 mg.kg-1.h-1) was given IV during opioid infusion to half of the rats. Cerebral perfusion-fixation with formalin was performed 24 h later, followed by histopathologic assessment. None of the control rats showed any histologic abnormalities. Overall summed neuropathologic severity was worse in opioid treated groups (P = 0.01). Lesions occurred primarily in cortical regions and limbic system structures. When arterial blood pressure was controlled to a lower level with hexamethonium (147 vs 100 mm Hg), rats had less severe lesions (P = 0.02). These data indicate that fentanyl, sufentanil, and alfentanil all can produce histopathologic evidence of brain injury in rats mitigated by hexamethonium.

Positron emission tomography reveals correlations between brain metabolism and mood changes in hyperthyroidism.

PubMed

Schreckenberger, M F; Egle, U T; Drecker, S; Buchholz, H G; Weber, M M; Bartenstein, P; Kahaly, G J

2006-12-01

Hyperthyroidism is frequently associated with emotional distress. The underlying cerebral processes of the endocrine-induced mood changes are unclear. The objective of this study was to investigate, for the first time, the neuronal correlates of thyrotoxicosis-associated psychic symptoms using positron emission tomography (PET). The study was designed as a cross-sectional trial. The study was performed at joint nuclear medicine and thyroid clinics. Twelve patients with untreated Graves' hyperthyroidism were evaluated. Levels of emotional distress were self-rated by means of the Hospital Anxiety and Depression Scale. Both patients and 20 age- and gender-matched euthyroid controls underwent a brain fluorodeoxyglucose PET scan. Subsequently, the functional relationship between brain metabolism and the psychometric scores was analyzed. Compared with controls and visualized by fluorodeoxyglucose PET, hyperthyroid patients showed a decreased (P < 0.0001) glucose metabolism in the limbic system (uncus and inferior temporal gyrus). Activation foci in the posterior cingulate and in the inferior parietal lobe were correlated with both anxiety and depression scales (P < 0.001). Compared with patients with normal anxiety levels, those with increased anxiety yielded an enhanced glucose metabolism (P < 0.001) in the bilateral sensory association cortex. Serum free T3/free T4 levels negatively correlated with regional glucose metabolism in the medial posterior cingulate. Thyrotoxicosis and associated psychic symptoms are correlated to regional metabolic changes in the main structures of the limbic/paralimbic system.

Brain limbic system-based intelligent controller application to lane change manoeuvre

NASA Astrophysics Data System (ADS)

Kim, Changwon; Langari, Reza

2011-12-01

This paper presents the application of a novel neuromorphic control strategy for lane change manoeuvres in the highway environment. The lateral dynamics of a vehicle with and without wind disturbance are derived and utilised to implement a control strategy based on the brain limbic system. To show the robustness of the proposed controller, several disturbance conditions including wind, uncertainty in the cornering stiffness, and changes in the vehicle mass are investigated. To demonstrate the performance of the suggested strategy, simulation results of the proposed method are compared with the human driver model-based control scheme, which has been discussed in the literature. The simulation results demonstrate the superiority of the proposed controller in energy efficiency, driving comfort, and robustness.

Modulation of Limbic and Prefrontal Connectivity by Electroconvulsive Therapy in Treatment-resistant Depression: A Preliminary Study.

PubMed

Cano, Marta; Cardoner, Narcís; Urretavizcaya, Mikel; Martínez-Zalacaín, Ignacio; Goldberg, Ximena; Via, Esther; Contreras-Rodríguez, Oren; Camprodon, Joan; de Arriba-Arnau, Aida; Hernández-Ribas, Rosa; Pujol, Jesús; Soriano-Mas, Carles; Menchón, José M

2016-01-01

Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. Longitudinal intralimbic and limbic-prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. An early significant intralimbic FC decrease significantly predicted a later increase in limbic-prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic-prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhanced limbic/impaired cortical-loop connection onto the hippocampus of NHE rats: Application of resting-state functional connectivity in a preclinical ADHD model.

PubMed

Zoratto, F; Palombelli, G M; Ruocco, L A; Carboni, E; Laviola, G; Sadile, A G; Adriani, W; Canese, R

2017-08-30

Due to a hyperfunctioning mesocorticolimbic system, Naples-High-Excitability (NHE) rats have been proposed to model for the meso-cortical variant of attention deficit/hyperactivity disorder (ADHD). Compared to Naples Random-Bred (NRB) controls, NHE rats show hyperactivity, impaired non-selective attention (Aspide et al., 1998), and impaired selective spatial attention (Ruocco et al., 2009a, 2014). Alteration in limbic functions has been proposed; however, resulting unbalance among forebrain areas has not been assessed yet. By resting-state functional Magnetic-Resonance Imaging (fMRI) in vivo, we investigated the connectivity of neuronal networks belonging to limbic vs. cortical loops in NHE and NRB rats (n=10 each). Notably, resting-state fMRI was applied using a multi-slice sagittal, gradient-echo sequence. Voxel-wise connectivity maps at rest, based on temporal correlation among fMRI time-series, were computed by seeding the hippocampus (Hip), nucleus accumbens (NAcc), dorsal striatum (dStr), amygdala (Amy) and dorsal/medial prefrontal cortex (PFC), both hemispheres. To summarize patterns of altered connection, clearly directional connectivity was evident within the cortical loop: bilaterally and specularly, from orbital and dorsal PFCs through dStr and hence towards Hip. Such network communication was reduced in NHE rats (also, with less mesencephalic/pontine innervation). Conversely, enhanced network activity emerged within the limbic loop of NHE rats: from left PFC, both through the NAcc and directly, to the Hip (all of which received greater ventral tegmental innervation, likely dopamine). Together with tuned-down cortical loop, this potentiated limbic loop may serve a major role in controlling ADHD-like behavioral symptoms in NHE rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Perirhinal cortex and temporal lobe epilepsy

PubMed Central

Biagini, Giuseppe; D'Antuono, Margherita; Benini, Ruba; de Guzman, Philip; Longo, Daniela; Avoli, Massimo

2013-01-01

The perirhinal cortex—which is interconnected with several limbic structures and is intimately involved in learning and memory—plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus. PMID:24009554

The hippocampus is an integral part of the temporal limbic system during emotional processing. Comment on "The quartet theory of human emotions: An integrative and neurofunctional model" by S. Koelsch et al.

NASA Astrophysics Data System (ADS)

Trost, Wiebke; Frühholz, Sascha

2015-06-01

The proposed quartet theory of human emotions by Koelsch and colleagues [1] identifies four different affect systems to be involved in the processing of particular types of emotions. Moreover, the theory integrates both basic emotions and more complex emotion concepts, which include also aesthetic emotions such as musical emotions. The authors identify a particular brain system for each kind of emotion type, also by contrasting them to brain structures that are generally involved in emotion processing irrespective of the type of emotion. A brain system that has been less regarded in emotion theories, but which represents one of the four systems of the quartet to induce attachment related emotions, is the hippocampus.

A Primary Role for Nucleus Accumbens and Related Limbic Network in Vocal Tics.

PubMed

McCairn, Kevin W; Nagai, Yuji; Hori, Yukiko; Ninomiya, Taihei; Kikuchi, Erika; Lee, Ju-Young; Suhara, Tetsuya; Iriki, Atsushi; Minamimoto, Takafumi; Takada, Masahiko; Isoda, Masaki; Matsumoto, Masayuki

2016-01-20

Inappropriate vocal expressions, e.g., vocal tics in Tourette syndrome, severely impact quality of life. Neural mechanisms underlying vocal tics remain unexplored because no established animal model representing the condition exists. We report that unilateral disinhibition of the nucleus accumbens (NAc) generates vocal tics in monkeys. Whole-brain PET imaging identified prominent, bilateral limbic cortico-subcortical activation. Local field potentials (LFPs) developed abnormal spikes in the NAc and the anterior cingulate cortex (ACC). Vocalization could occur without obvious LFP spikes, however, when phase-phase coupling of alpha oscillations were accentuated between the NAc, ACC, and the primary motor cortex. These findings contrasted with myoclonic motor tics induced by disinhibition of the dorsolateral putamen, where PET activity was confined to the ipsilateral sensorimotor system and LFP spikes always preceded motor tics. We propose that vocal tics emerge as a consequence of dysrhythmic alpha coupling between critical nodes in the limbic and motor networks. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping brain circuits of reward and motivation: in the footsteps of Ann Kelley.

PubMed

Richard, Jocelyn M; Castro, Daniel C; Difeliceantonio, Alexandra G; Robinson, Mike J F; Berridge, Kent C

2013-11-01

Ann Kelley was a scientific pioneer in reward neuroscience. Her many notable discoveries included demonstrations of accumbens/striatal circuitry roles in eating behavior and in food reward, explorations of limbic interactions with hypothalamic regulatory circuits, and additional interactions of motivation circuits with learning functions. Ann Kelley's accomplishments inspired other researchers to follow in her footsteps, including our own laboratory group. Here we describe results from several lines of our research that sprang in part from earlier findings by Kelley and colleagues. We describe hedonic hotspots for generating intense pleasure 'liking', separate identities of 'wanting' versus 'liking' systems, a novel role for dorsal neostriatum in generating motivation to eat, a limbic keyboard mechanism in nucleus accumbens for generating intense desire versus intense dread, and dynamic limbic transformations of learned memories into motivation. We describe how origins for each of these themes can be traced to fundamental contributions by Ann Kelley. Copyright © 2013 Elsevier Ltd. All rights reserved.

Right fronto-limbic atrophy is associated with reduced empathy in refractory unilateral mesial temporal lobe epilepsy.

PubMed

Toller, Gianina; Adhimoolam, Babu; Rankin, Katherine P; Huppertz, Hans-Jürgen; Kurthen, Martin; Jokeit, Hennric

2015-11-01

Refractory mesial temporal lobe epilepsy (MTLE) is the most frequent focal epilepsy and is often accompanied by deficits in social cognition including emotion recognition, theory of mind, and empathy. Consistent with the neuronal networks that are crucial for normal social-cognitive processing, these impairments have been associated with functional changes in fronto-temporal regions. However, although atrophy in unilateral MTLE also affects regions of the temporal and frontal lobes that underlie social cognition, little is known about the structural correlates of social-cognitive deficits in refractory MTLE. In the present study, a psychometrically validated empathy questionnaire was combined with whole-brain voxel-based morphometry (VBM) to investigate the relationship between self-reported affective and cognitive empathy and gray matter volume in 55 subjects (13 patients with right MTLE, 9 patients with left MTLE, and 33 healthy controls). Consistent with the brain regions underlying social cognition, our results show that lower affective and cognitive empathy was associated with smaller volume in predominantly right fronto-limbic regions, including the right hippocampus, parahippocampal gyrus, thalamus, fusiform gyrus, inferior temporal gyrus, dorsomedial and dorsolateral prefrontal cortices, and in the bilateral midbrain. The only region that was associated with both affective and cognitive empathy was the right mesial temporal lobe. These findings indicate that patients with right MTLE are at increased risk for reduced empathy towards others' internal states and they shed new light on the structural correlates of impaired social cognition frequently accompanying refractory MTLE. In line with previous evidence from patients with neurodegenerative disease and stroke, the present study suggests that empathy depends upon the integrity of right fronto-limbic and brainstem regions and highlights the importance of the right mesial temporal lobe and midbrain structures for human empathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Spatial Cognition and Episodic Memory Formation in the Limbic Cortex].

PubMed

Kobayashi, Yasushi

2017-04-01

The limbic lobe defined by Broca is a cortical region with highly diverse structure and functions, and comprises the paleo-, archi-, and neocortices as well as their transitional zones. In the limbic lobe, Brodmann designated areas 27, 28, 34, 35, and 36 adjacent to the hippocampus, and areas 23, 24, 25, 26, 29, 30, 31, 32, and 33 around the corpus callosum. In the current literature, areas 27 and 28 correspond to the presubiculum and entorhinal cortex, respectively. Area 34 represents the cortico-medial part of the amygdaloid complex. Areas 35 and 36 roughly cover the perirhinal and parahippocampal cortices. Areas 24, 25, 32, and 33 belong to the anterior cingulate gyrus, while areas 23, 26, 29, 30, and 31 to the posterior cingulate gyrus. Areas 25, 32, and the anteroinferior portion of area 24 are deeply involved in emotional responses, particularly in their autonomic functions, through reciprocal connections with the amygdaloid complex, anterior thalamus and projections to the brainstem and spinal visceral centers. Areas 29 and 30 have dense reciprocal connections with areas 23 and 31, the dorsolateral prefrontal areas, and the regions related to the hippocampus. They play pivotal roles in mediating spatial cognition, working memory processing, and episodic memory formation.

Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy.

PubMed

Raine, Adrian; Lee, Lydia; Yang, Yaling; Colletti, Patrick

2010-09-01

Antisocial personality disorder and psychopathy have been hypothesised to have a neurodevelopmental basis, but this proposition has not been formally tested. This study tests the hypothesis that individuals with cavum septum pellucidum (CSP), a marker of limbic neural maldevelopment, will show higher levels of psychopathy and antisocial personality. Cavum septum pellucidum was assessed using anatomical magnetic resonance imaging in a community sample. Those with CSP (n = 19) were compared with those lacking CSP (n = 68) on antisocial personality, psychopathy and criminal offending. Those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls. The pervasiveness of this association was indicated by the fact that those lacking a diagnosis of antisocial personality disorder, but who were charged or convicted for an offence, had a more extensive CSP than non-antisocial controls. Results could not be attributed to prior trauma exposure, head injury, demographic factors or comorbid psychiatric conditions. Our findings appear to be the first to provide evidence for a neurodevelopmental brain abnormality in those with antisocial personality disorder and psychopathy, and support the hypothesis that early maldevelopment of limbic and septal structures predisposes to the spectrum of antisocial behaviours.

Oxidative metabolism of limbic structures after acute administration of diazepam, alprazolam and zolpidem.

PubMed

González-Pardo, Héctor; Conejo, Nélida M; Arias, Jorge L

2006-08-30

The effects of acute administration of two benzodiazepines and a non-benzodiazepine hypnotic on behavior and brain metabolism were evaluated in rats. After testing the behavioral action of the benzodiazepines on the open field and the elevated plus-maze, the effects of the three drugs on neuronal metabolism of particular limbic regions were measured using cytochrome c oxidase (CO) histochemistry. Diazepam (5 mg/kg i.p.) and alprazolam (0.5 mg/kg i.p.) induced clear anxiolytic effects and a decrease in locomotion, whereas zolpidem (2 mg/kg i.p.) caused an intense hypnotic effect. The anxiolytic effects of alprazolam were distinguishable from diazepam due to the pharmacological and clinical profile of this triazolobenzodiazepine. CO activity decreased significantly in almost all the limbic regions evaluated after zolpidem administration. However, significant prominent decreases in CO activity were found after diazepam treatment in the medial mammillary nucleus, anteroventral thalamus, cingulate cortex, dentate gyrus and basolateral amygdala. Alprazolam caused similar decreases in CO activity, with the exception of the prelimbic and cingulate cortices, where significant increases were detected. In agreement with previous studies using other functional mapping techniques, our results indicate that particular benzodiazepines and non-benzodiazepine hypnotics induce selective changes in brain oxidative metabolism.

Neurodevelopmental marker for limbic maldevelopment in antisocial personality disorder and psychopathy

PubMed Central

Raine, Adrian; Lee, Lydia; Yang, Yaling; Colletti, Patrick

2010-01-01

Background Antisocial personality disorder and psychopathy have been hypothesised to have a neurodevelopmental basis, but this proposition has not been formally tested. Aims This study tests the hypothesis that individuals with cavum septum pellucidum (CSP), a marker of limbic neural maldevelopment, will show higher levels of psychopathy and antisocial personality. Method Cavum septum pellucidum was assessed using anatomical magnetic resonance imaging in a community sample. Those with CSP (n = 19) were compared with those lacking CSP (n = 68) on antisocial personality, psychopathy and criminal offending. Results Those with CSP had significantly higher levels of antisocial personality, psychopathy, arrests and convictions compared with controls. The pervasiveness of this association was indicated by the fact that those lacking a diagnosis of antisocial personality disorder, but who were charged or convicted for an offence, had a more extensive CSP than non-antisocial controls. Results could not be attributed to prior trauma exposure, head injury, demographic factors or comorbid psychiatric conditions. Conclusions Our findings appear to be the first to provide evidence for a neurodevelopmental brain abnormality in those with antisocial personality disorder and psychopathy, and support the hypothesis that early maldevelopment of limbic and septal structures predisposes to the spectrum of antisocial behaviours. PMID:20807962

Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST

EPA Science Inventory

Alterations in hypothalamic–pituitary–adrenal axis function contribute to many of the adverse behavioral effects of chronic voluntary alcohol drinking, including alcohol dependence and mood disorders; limbic brain structures such as the bed nucleus of the stria termin...

Targeted transcranial theta-burst stimulation alters fronto-insular network and prefrontal GABA.

PubMed

Iwabuchi, Sarina J; Raschke, Felix; Auer, Dorothee P; Liddle, Peter F; Lankappa, Sudheer T; Palaniyappan, Lena

2017-02-01

Repetitive transcranial magnetic stimulation (rTMS) has been used worldwide to treat depression. However, the exact physiological effects are not well understood. Pathophysiology of depression involves crucial limbic structures (e.g. insula), and it is still not clear if these structures can be modulated through neurostimulation of surface regions (e.g. dorsolateral prefrontal cortex, DLPFC), and whether rTMS-induced excitatory/inhibitory transmission alterations relate to fronto-limbic connectivity changes. Therefore, we sought proof-of-concept for neuromodulation of insula via prefrontal intermittent theta-burst stimulation (iTBS), and how these effects relate to GABAergic and glutamatergic systems. In 27 healthy controls, we employed a single-blind crossover randomised-controlled trial comparing placebo and real iTBS using resting-state functional MRI and magnetic resonance spectroscopy. Granger causal analysis was seeded from right anterior insula (rAI) to locate individualized left DLPFC rTMS targets. Effective connectivity coefficients within rAI and DLPFC were calculated, and levels of GABA/Glx, GABA/Cr and Glx/Cr in DLPFC and anterior cingulate voxels were also measured. ITBS significantly dampened fronto-insular connectivity and reduced GABA/Glx in both voxels. GABA/Glx had a significant mediating effect on iTBS-induced changes in DLPFC-to-rAI connectivity. We demonstrate modulation of the rAI using targeted iTBS through alterations of excitatory/inhibitory interactions, which may underlie therapeutic effects of rTMS, offering promise for rTMS treatment optimization. Copyright © 2016 Elsevier Inc. All rights reserved.

Repetitive behaviors in autism are linked to imbalance of corticostriatal connectivity: a functional connectivity MRI study.

PubMed

Abbott, Angela E; Linke, Annika C; Nair, Aarti; Jahedi, Afrooz; Alba, Laura A; Keown, Christopher L; Fishman, Inna; Müller, Ralph-Axel

2018-01-01

The neural underpinnings of repetitive behaviors (RBs) in autism spectrum disorders (ASDs), ranging from cognitive to motor characteristics, remain unknown. We assessed RB symptomatology in 50 ASD and 52 typically developing (TD) children and adolescents (ages 8-17 years), examining intrinsic functional connectivity (iFC) of corticostriatal circuitry, which is important for reward-based learning and integration of emotional, cognitive and motor processing, and considered impaired in ASDs. Connectivity analyses were performed for three functionally distinct striatal seeds (limbic, frontoparietal and motor). Functional connectivity with cortical regions of interest was assessed for corticostriatal circuit connectivity indices and ratios, testing the balance of connectivity between circuits. Results showed corticostriatal overconnectivity of limbic and frontoparietal seeds, but underconnectivity of motor seeds. Correlations with RBs were found for connectivity between the striatal motor seeds and cortical motor clusters from the whole-brain analysis, and for frontoparietal/limbic and motor/limbic connectivity ratios. Division of ASD participants into high (n = 17) and low RB subgroups (n = 19) showed reduced frontoparietal/limbic and motor/limbic circuit ratios for high RB compared to low RB and TD groups in the right hemisphere. Results suggest an association between RBs and an imbalance of corticostriatal iFC in ASD, being increased for limbic, but reduced for frontoparietal and motor circuits. © The Author (2017). Published by Oxford University Press.

Repetitive behaviors in autism are linked to imbalance of corticostriatal connectivity: a functional connectivity MRI study

PubMed Central

Abbott, Angela E; Linke, Annika C; Nair, Aarti; Jahedi, Afrooz; Alba, Laura A; Keown, Christopher L; Fishman, Inna

2018-01-01

Abstract The neural underpinnings of repetitive behaviors (RBs) in autism spectrum disorders (ASDs), ranging from cognitive to motor characteristics, remain unknown. We assessed RB symptomatology in 50 ASD and 52 typically developing (TD) children and adolescents (ages 8–17 years), examining intrinsic functional connectivity (iFC) of corticostriatal circuitry, which is important for reward-based learning and integration of emotional, cognitive and motor processing, and considered impaired in ASDs. Connectivity analyses were performed for three functionally distinct striatal seeds (limbic, frontoparietal and motor). Functional connectivity with cortical regions of interest was assessed for corticostriatal circuit connectivity indices and ratios, testing the balance of connectivity between circuits. Results showed corticostriatal overconnectivity of limbic and frontoparietal seeds, but underconnectivity of motor seeds. Correlations with RBs were found for connectivity between the striatal motor seeds and cortical motor clusters from the whole-brain analysis, and for frontoparietal/limbic and motor/limbic connectivity ratios. Division of ASD participants into high (n = 17) and low RB subgroups (n = 19) showed reduced frontoparietal/limbic and motor/limbic circuit ratios for high RB compared to low RB and TD groups in the right hemisphere. Results suggest an association between RBs and an imbalance of corticostriatal iFC in ASD, being increased for limbic, but reduced for frontoparietal and motor circuits. PMID:29177509

Sex dimorphism in a mediatory role of the posterior midcingulate cortex in the association between anxiety and pain sensitivity.

PubMed

Kisler, Lee-Bareket; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone; Weissman-Fogel, Irit

2016-11-01

Behavioral studies found greater pain sensitivity in females that vanishes fully or partially when controlling for the emotional state. Furthermore, pain-related brain activation hints at the role of limbic structures in sex differences in pain processing. We aimed to investigate the role of pain-related limbic structures in mediating the relation between subjects' affective state (i.e., anxiety) and pain. Contact heat-evoked potentials (CHEPs) were recorded in 26 healthy subjects (13 males) simultaneously with innocuous (42 °C) baseline and target noxious (52 °C) series of stimuli administered to the left non-dominant volar forearm. The N2 and P2 components were analyzed, and their generators' activity was estimated using standardized low-resolution brain electromagnetic tomography. Thereafter, structural equation modeling (SEM) was applied separately for females and males, examining the mediatory role of the CHEPs' limbic structures generators [posterior midcingulate cortex (pMCC), insula, amygdala, and hippocampus] in the anxiety-pain sensitivity association. Females exhibited greater P2 amplitudes that were highly associated with larger pMCC activity (r = 0.910, p < 0.001). This correlation was also evident in males, though with less strength (r = 0.578, p = 0.039). Moreover, the P2 amplitudes were associated both in females (r = 0.645, p = 0.017) and males (r = 0.608, p = 0.028) with the activity of the amygdala\\hippocampus\\insula. SEM revealed that the relationship between state anxiety and pain ratings was only in females fully mediated via the effect of the pMCC on the P2 amplitude. These findings suggest that sexual dimorphism in anxiety-related brain activity may explain the differences found in CHEPs and the sex-related association between anxiety and pain.

Differentially categorized structural brain hubs are involved in different microstructural, functional, and cognitive characteristics and contribute to individual identification.

PubMed

Wang, Xindi; Lin, Qixiang; Xia, Mingrui; He, Yong

2018-04-01

Very little is known regarding whether structural hubs of human brain networks that enable efficient information communication may be classified into different categories. Using three multimodal neuroimaging data sets, we construct individual structural brain networks and further identify hub regions based on eight widely used graph-nodal metrics, followed by comprehensive characteristics and reproducibility analyses. We show the three categories of structural hubs in the brain network, namely, aggregated, distributed, and connector hubs. Spatially, these distinct categories of hubs are primarily located in the default-mode system and additionally in the visual and limbic systems for aggregated hubs, in the frontoparietal system for distributed hubs, and in the sensorimotor and ventral attention systems for connector hubs. These categorized hubs exhibit various distinct characteristics to support their differentiated roles, involving microstructural organization, wiring costs, topological vulnerability, functional modular integration, and cognitive flexibility; moreover, these characteristics are better in the hubs than nonhubs. Finally, all three categories of hubs display high across-session spatial similarities and act as structural fingerprints with high predictive rates (100%, 100%, and 84.2%) for individual identification. Collectively, we highlight three categories of brain hubs with differential microstructural, functional and, cognitive associations, which shed light on topological mechanisms of the human connectome. © 2018 Wiley Periodicals, Inc.

Working memory overload: fronto-limbic interactions and effects on subsequent working memory function.

PubMed

Yun, Richard J; Krystal, John H; Mathalon, Daniel H

2010-03-01

The human working memory system provides an experimentally useful model for examination of neural overload effects on subsequent functioning of the overloaded system. This study employed functional magnetic resonance imaging in conjunction with a parametric working memory task to characterize the behavioral and neural effects of cognitive overload on subsequent cognitive performance, with particular attention to cognitive-limbic interactions. Overloading the working memory system was associated with varying degrees of subsequent decline in performance accuracy and reduced activation of brain regions central to both task performance and suppression of negative affect. The degree of performance decline was independently predicted by three separate factors operating during the overload condition: the degree of task failure, the degree of amygdala activation, and the degree of inverse coupling between the amygdala and dorsolateral prefrontal cortex. These findings suggest that vulnerability to overload effects in cognitive functioning may be mediated by reduced amygdala suppression and subsequent amygdala-prefrontal interaction.

Neurobiology of emotions: an update.

PubMed

Esperidião-Antonio, Vanderson; Majeski-Colombo, Marilia; Toledo-Monteverde, Diana; Moraes-Martins, Glaciele; Fernandes, Juliana José; Bauchiglioni de Assis, Marjorie; Montenegro, Stefânia; Siqueira-Batista, Rodrigo

2017-06-01

The 'nature' of emotions is one of the archaic themes of Western thought, thematized in different cultural manifestations - such as art, science, philosophy, myths and religion -, since Ancient times. In the last decades, the advances in neurosciences have permitted the construction of hypotheses that explain emotions, especially through the studies involving the limbic system. To present an updated discussion about the neurobiology of processes relating to emotions - focusing (1) on the main neural structures that relate to emotions, (2) the paths and circuits of greater relevance, (3) the implicated neurotransmitters, (4) the connections that possess neurovegetative control and (5) the discussion about the main emotions - is the objective of this present article.

Treatment of VGKC complex antibody-associated limbic encephalitis: a systematic review.

PubMed

Radja, Guirindhra Koumar; Cavanna, Andrea Eugenio

2013-01-01

Limbic encephalitis is an autoimmune neuropsychiatric condition characterized by subacute cognitive symptoms, seizures, and affective changes. Although limbic encephalitis is usually caused by an immune reaction secondary to neoplasms, different types of potentially treatable non-paraneoplastic limbic encephalitis (nPLE) have recently been described. In particular, published studies have reported variable responses to immunosuppressive therapy in Voltage-Gated Potassium Channel (VGKC) complex antibody-associated nPLE. This systematic literature review found that the most significant improvements were reported by patients presenting with affective symptoms and consistent neuroradiological changes. In these patients, improved clinical outcomes correlated with the largest decreases in antibody titers.

A voxel based comparative analysis using magnetization transfer imaging and T1-weighted magnetic resonance imaging in progressive supranuclear palsy

PubMed Central

Sandhya, Mangalore; Saini, Jitender; Pasha, Shaik Afsar; Yadav, Ravi; Pal, Pramod Kumar

2014-01-01

Aims: In progressive supranuclear palsy (PSP) tissue damage occurs in specific cortical and subcortical regions. Voxel based analysis using T1-weighted images depict quantitative gray matter (GM) atrophy changes. Magnetization transfer (MT) imaging depicts qualitative changes in the brain parenchyma. The purpose of our study was to investigate whether MT imaging could indicate abnormalities in PSP. Settings and Design: A total of 10 patients with PSP (9 men and 1 woman) and 8 controls (5 men and 3 women) were studied with T1-weighted magnetic resonance imaging (MRI) and 3DMT imaging. Voxel based analysis of T1-weighted MRI was performed to investigate brain atrophy while MT was used to study qualitative abnormalities in the brain tissue. We used SPM8 to investigate group differences (with two sample t-test) using the GM and white matter (WM) segmented data. Results: T1-weighted imaging and MT are equally sensitive to detect changes in GM and WM in PSP. Magnetization transfer ratio images and magnetization-prepared rapid acquisition of gradient echo revealed extensive bilateral volume and qualitative changes in the orbitofrontal, prefrontal cortex and limbic lobe and sub cortical GM. The prefrontal structures involved were the rectal gyrus, medial, inferior frontal gyrus (IFG) and middle frontal gyrus (MFG). The anterior cingulate, cingulate gyrus and lingual gyrus of limbic lobe and subcortical structures such as caudate, thalamus, insula and claustrum were also involved. Cerebellar involvement mainly of anterior lobe was also noted. Conclusions: The findings suggest that voxel based MT imaging permits a whole brain unbiased investigation of central nervous system structural integrity in PSP. PMID:25024571

Reduced functional connectivity within the limbic cortico-striato-thalamo-cortical loop in unmedicated adults with obsessive-compulsive disorder.

PubMed

Posner, Jonathan; Marsh, Rachel; Maia, Tiago V; Peterson, Bradley S; Gruber, Allison; Simpson, H Blair

2014-06-01

Cortico-striato-thalamo-cortical (CSTC) loops project from the cortex to the striatum, then from the striatum to the thalamus via the globus pallidus, and finally from the thalamus back to the cortex again. These loops have been implicated in Obsessive-Compulsive Disorder (OCD) with particular focus on the limbic CSTC loop, which encompasses the orbitofrontal and anterior cingulate cortices, as well as the ventral striatum. Resting state functional-connectivity MRI (rs-fcMRI) studies, which examine temporal correlations in neural activity across brain regions at rest, have examined CSTC loop connectivity in patients with OCD and suggest hyperconnectivity within these loops in medicated adults with OCD. We used rs-fcMRI to examine functional connectivity within CSTC loops in unmedicated adults with OCD (n = 23) versus healthy controls (HCs) (n = 20). Contrary to prior rs-fcMRI studies in OCD patients on medications that report hyperconnectivity in the limbic CSTC loop, we found that compared with HCs, unmedicated OCD participants had reduced connectivity within the limbic CSTC loop. Exploratory analyses revealed that reduced connectivity within the limbic CSTC loop correlated with OCD symptom severity in the OCD group. Our finding of limbic loop hypoconnectivity in unmedicted OCD patients highlights the potential confounding effects of antidepressants on connectivity measures and the value of future examinations of the effects of pharmacological and/or behavioral treatments on limbic CSTC loop connectivity. Copyright © 2013 Wiley Periodicals, Inc.

Aberrant Paralimbic Gray Matter in Incarcerated Male Adolescents with Psychopathic Traits

ERIC Educational Resources Information Center

Ermer, Elsa; Cope, Lora M.; Nyalakanti, Prashanth K.; Calhoun, Vince D.; Kiehl, Kent A.

2013-01-01

Objective: To investigate the relationship between brain structure and psychopathic traits in maximum-security incarcerated male adolescents, and to examine whether the associations between brain volumes in paralimbic and limbic regions and psychopathic traits observed in incarcerated adult men extend to an independent sample of incarcerated male…

Shared effects of the clusterin gene on the default mode network among individuals at risk for Alzheimer's disease.

PubMed

Ye, Qing; Su, Fan; Shu, Hao; Gong, Liang; Xie, Chun-Ming; Zhou, Hong; Zhang, Zhi-Jun; Bai, Feng

2017-05-01

To explore the common effects of the clusterin (CLU) rs11136000 variant on the default mode network (DMN) in amnestic mild cognitive impairment (aMCI) subjects and remitted geriatric depression (RGD) subjects. Fifty-one aMCI subjects, 38 RGD subjects, and 64 cognitively normal elderly subjects underwent resting-state fMRI scans and neuropsychological tests at both baseline and a 35-month follow-up. Posterior cingulate cortex seed-based functional connectivity (FC) analysis was used to obtain the DMN patterns. A CLU gene×disease×time interaction for aMCI subjects was mainly detected in the core cortical midline structures of the DMN, and the interaction for RGD subjects was mainly detected in the limbic system. However, they overlapped in two frontal regions, where consistent effects of the CLU gene on FC alterations were found between aMCI and RGD groups. Furthermore, the alterations of FC with frontal, parietal, and limbic regions compensated for episodic memory impairments in CLU-CT/TT carriers, while no such compensation was found in CLU-CC carriers. The CLU gene could consistently affect the DMN FC with frontal regions among individuals at risk for Alzheimer's disease, and the CLU-T allele was associated with more compensatory neural processes in DMN changes. © 2017 John Wiley & Sons Ltd.

Cannabinoid modulation of prefrontal-limbic activation during fear extinction learning and recall in humans

PubMed Central

Rabinak, Christine A.; Angstadt, Mike; Lyons, Maryssa; Mori, Shoko; Milad, Mohammed R.; Liberzon, Israel; Phan, K. Luan

2013-01-01

Pre-extinction administration of ∆9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely involves via enhancement of the cannabinoid system within the ventromedial prefrontal cortex (vmPFC) and hippocampus (HIPP), brain structures critical to fear extinction. However, the effect of cannabinoids on the underlying neural circuitry of extinction memory recall in humans has not been demonstrated. We conducted a functional magnetic resonance imaging (fMRI) study using a randomized, double-blind, placebo-controlled, between-subjects design (N=14/group) coupled with a standard Pavlovian fear extinction paradigm and an acute pharmacological challenge with oral dronabinol (synthetic THC) in healthy adult volunteers. We examined the effects of THC on vmPFC and HIPP activation when tested for recall of extinction learning 24 hours after extinction learning. Compared to subjects who received placebo, participants who received THC showed increased vmPFC and HIPP activation to a previously extinguished conditioned stimulus (CS+E) during extinction memory recall. This study provides the first evidence that pre-extinction administration of THC modulates prefrontal-limbic circuits during fear extinction in humans and prompts future investigation to test if cannabinoid agonists can rescue or correct the impaired behavioral and neural function during extinction recall in patients with PTSD. Ultimately, the cannabinoid system may serve as a promising target for innovative intervention strategies (e.g. pharmacological enhancement of exposure-based therapy) in PTSD and other fear learning-related disorders. PMID:24055595

Current hypotheses on the mechanisms of alcoholism.

PubMed

Vetreno, R P; Crews, F T

2014-01-01

Chronic use of alcohol results in progressive changes to brain and behavior that often lead to the development of alcohol dependence and alcoholism. Although the mechanisms underlying the development of alcoholism remain to be fully elucidated, diminished executive functioning due to hypoactive prefrontal cortex executive control and hyperactive limbic system anxiety and negative emotion might contribute mechanistically to the shift from experimental use to alcoholism and dependence. In the chapter that follows, behavioral deficits associated with cortical dysfunction and neurodegeneration will be related to the behavioral characteristics of alcoholism (e.g., diminished executive function, impulsivity, altered limbic modulation). We will provide evidence that alterations in cyclic AMP-responsive element binding protein (CREB: neurotrophic) and NF-κB (neuroimmune) signaling contribute to the development and persistence of alcoholism. In addition, genetic predispositions and an earlier age of drinking onset will be discussed as contributing factors to the development of alcohol dependence and alcoholism. Overall chronic ethanol-induced neuroimmune gene induction is proposed to alter limbic and frontal neuronal networks contributing to the development and persistence of alcoholism. © 2014 Elsevier B.V. All rights reserved.

Organizational effects of diethylstilbestrol on brain vasotocin and sexual behavior in male quail.

PubMed

Viglietti-Panzica, Carla; Montoncello, Barbara; Mura, Elena; Pessatti, Marzia; Panzica, GianCarlo

2005-04-15

In Japanese quail, we previously described a sexual dimorphism of the parvocellular vasotocin system of the limbic region that, as the reproductive behavior, is steroid-sensitive and is organized during embryonic life by the exposure to estradiol. We verified in this study whether diethylstilbestrol, a chemical xenoestrogen, has analogous organizational effects on the vasotocin system of limbic regions and on copulatory behavior of male Japanese quail. We injected in the yolk sac of 3 day-old quail embryos diethylstilbestrol or estradiol benzoate (a treatment which suppresses male copulatory behavior in adulthood and reduces vasotocin innervation), or sesame oil (control). No further hormonal manipulations were performed after hatching. Sexual behavior was recorded in males at the age of 6 weeks. Estradiol- and diethylstilbestrol-treated males exhibited a total suppression of copulatory behavior. After behavioral tests, all males were sacrificed and brain sections processed for vasotocin immunocytochemistry. Significant decrease in the density of vasotocin immunoreactivity was detected in the medial preoptic nucleus, in the bed nucleus of stria terminalis, and in the lateral septum of diethylstilbestrol-treated males. The magnocellular vasotocin neurons were, in contrast, not affected. In conclusion, the present data demonstrate that embryonic treatment with diethylstilbestrol induces a full sex reversal of behavioral phenotype as well as a significant decrease of vasotocin expression in the preoptic-limbic region in male Japanese quail. Therefore, the parvocellular vasotocin system could represent an optimal model to investigate the effects of pollutants on neural circuits controlling reproductive functions.

Alterations of local cerebral glucose utilization in lean and obese fa/fa rats after acute adrenalectomy.

PubMed

Doyle, P; Rohner-Jeanrenaud, F; Jeanrenaud, B

1994-08-29

An animal model often used to investigate the aetiology of obesity is the genetically obese fa/fa rat. It has many abnormalities, including hyperphagia, hyper-insulinemia, insulin resistance, low cerebral glucose utilization and an overactive hypothalamo-pituitary adrenal (HPA) axis with resulting hypercorticism. Due to the latter consideration, the aim of this work was to study the impact of acute adrenalectomy (ADX) on the local cerebral glucose utilization (LCGU) of lean and obese fa/fa rats. ADX resulted in discrete increases in LCGU of regions common to both lean and obese rats. These common regions were found to belong to be related to the limbic system. Within this system, the LCGU of the brain of obese rats was either normalized to lean sham operated values or increased by ADX to a similar degree in both groups on a percentage basis. It was concluded that the LCGU of both lean and obese animals appears to be negatively regulated, albeit to different extents, by glucocorticoids. Such negative regulation is particularly salient within the limbic system of the lean rat and even more so in the fa/fa rat. It is suggested that the long-term hypercorticism of obese fa/fa rats due to abnormal regulation of the HPA axis may result in a decreased LCGU in limbic and related regions of the brain of fa/fa rats and contribute to the expression of the obese phenotype.

Compulsive sexual behavior: Prefrontal and limbic volume and interactions.

PubMed

Schmidt, Casper; Morris, Laurel S; Kvamme, Timo L; Hall, Paula; Birchard, Thaddeus; Voon, Valerie

2017-03-01

Compulsive sexual behaviors (CSB) are relatively common and associated with significant personal and social dysfunction. The underlying neurobiology is still poorly understood. The present study examines brain volumes and resting state functional connectivity in CSB compared with matched healthy volunteers (HV). Structural MRI (MPRAGE) data were collected in 92 subjects (23 CSB males and 69 age-matched male HV) and analyzed using voxel-based morphometry. Resting state functional MRI data using multi-echo planar sequence and independent components analysis (ME-ICA) were collected in 68 subjects (23 CSB subjects and 45 age-matched HV). CSB subjects showed greater left amygdala gray matter volumes (small volume corrected, Bonferroni adjusted P < 0.01) and reduced resting state functional connectivity between the left amygdala seed and bilateral dorsolateral prefrontal cortex (whole brain, cluster corrected FWE P < 0.05) compared with HV. CSB is associated with elevated volumes in limbic regions relevant to motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions. Future studies should aim to assess longitudinal measures to investigate whether these findings are risk factors that predate the onset of the behaviors or are consequences of the behaviors. Hum Brain Mapp 38:1182-1190, 2017. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Sensorimotor Modulation of Mood and Depression: In Search of an Optimal Mode of Stimulation

PubMed Central

Canbeyli, Resit

2013-01-01

Depression involves a dysfunction in an affective fronto-limbic circuitry including the prefrontal cortices, several limbic structures including the cingulate cortex, the amygdala, and the hippocampus as well as the basal ganglia. A major emphasis of research on the etiology and treatment of mood disorders has been to assess the impact of centrally generated (top-down) processes impacting the affective fronto-limbic circuitry. The present review shows that peripheral (bottom-up) unipolar stimulation via the visual and the auditory modalities as well as by physical exercise modulates mood and depressive symptoms in humans and animals and activates the same central affective neurocircuitry involved in depression. It is proposed that the amygdala serves as a gateway by articulating the mood regulatory sensorimotor stimulation with the central affective circuitry by emotionally labeling and mediating the storage of such emotional events in long-term memory. Since both amelioration and aggravation of mood is shown to be possible by unipolar stimulation, the review suggests that a psychophysical assessment of mood modulation by multimodal stimulation may uncover mood ameliorative synergisms and serve as adjunctive treatment for depression. Thus, the integrative review not only emphasizes the relevance of investigating the optimal levels of mood regulatory sensorimotor stimulation, but also provides a conceptual springboard for related future research. PMID:23908624

Limbic correlates of fearlessness and disinhibition in incarcerated youth: Exploring the brain-behavior relationship with the Hare Psychopathy Checklist: Youth Version.

PubMed

Walters, Glenn D; Kiehl, Kent A

2015-12-15

The purpose of this study was to determine whether scores on two temperament dimensions (fearlessness and disinhibition) correlated differentially with gray matter volumes in two limbic regions (amygdala and hippocampus). It was predicted that the fearlessness dimension would correlate with low gray matter volumes in the amygdala and the disinhibition dimension would correlate with low gray matter volumes in the hippocampus after controlling for age, IQ, regular substance use, and total brain volume. Participants were 191 male adolescents (age range=13-19 years) incarcerated in a maximum-security juvenile facility. Structural magnetic resonance imaging (MRI) analysis of the limbic and paralimbic regions of the brain was conducted. The temperament dimensions were estimated with items from the Psychopathy Checklist: Youth Version (PCL: YV: Forth et al., 2003). Analyses showed that the fearlessness dimension correlated negatively with gray matter volumes in the amygdala and the disinhibition dimension correlated negatively with gray matter volumes in the hippocampus but not vice versa. These findings provide preliminary support for the construct validity of the fearlessness and disinhibition temperament dimensions and offer confirmatory evidence for involvement of the amygdala and hippocampus in fear conditioning and behavioral inhibition, respectively. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Structural correlates of psychopathological symptom dimensions in schizophrenia: a voxel-based morphometric study.

PubMed

Koutsouleris, Nikolaos; Gaser, Christian; Jäger, Markus; Bottlender, Ronald; Frodl, Thomas; Holzinger, Silvia; Schmitt, Gisela J E; Zetzsche, Thomas; Burgermeister, Bernhard; Scheuerecker, Johanna; Born, Christine; Reiser, Maximilian; Möller, Hans-Jürgen; Meisenzahl, Eva M

2008-02-15

Structural neuroimaging has substantially advanced the neurobiological research of schizophrenia by describing a range of focal brain alterations as possible neuroanatomical underpinnings of the disease. Despite this progress, a considerable heterogeneity of structural findings persists that may reflect the phenomenological diversity of schizophrenia. It is unclear whether the range of possible clinical disease manifestations relates to a core structural brain deficit or to distinct structural correlates. Therefore, gray matter density (GMD) differences between 175 schizophrenic patients (SZ) and 177 matched healthy control subjects (HC) were examined in a three-step approach using cross-sectional and conjunctional voxel-based morphometry (VBM): (1) analysis of structural alterations irrespective of symptomatology; (2) subdivision of the patient sample according to a three-dimensional factor model of the PANSS and investigation of structural differences between these subsamples and healthy controls; (3) analysis of a common pattern of structural alterations present in all patient subsamples compared to healthy controls. Significant GMD reductions in patients compared to controls were identified within the prefrontal, limbic, paralimbic, temporal and thalamic regions. The disorganized symptom dimension was associated with bilateral alterations in temporal, insular and medial prefrontal cortices. Positive symptoms were associated with left-pronounced alterations in perisylvian regions and extended thalamic GMD losses. Negative symptoms were linked to the most extended alterations within orbitofrontal, medial prefrontal, lateral prefrontal and temporal cortices as well as limbic and subcortical structures. Thus, structural heterogeneity in schizophrenia may relate to specific patterns of GMD reductions that possibly share a common prefrontal-perisylvian pattern of structural brain alterations.

Ventral pallidum roles in reward and motivation.

PubMed

Smith, Kyle S; Tindell, Amy J; Aldridge, J Wayne; Berridge, Kent C

2009-01-23

In recent years the ventral pallidum has become a focus of great research interest as a mechanism of reward and incentive motivation. As a major output for limbic signals, the ventral pallidum was once associated primarily with motor functions rather than regarded as a reward structure in its own right. However, ample evidence now suggests that ventral pallidum function is a major mechanism of reward in the brain. We review data indicating that (1) an intact ventral pallidum is necessary for normal reward and motivation, (2) stimulated activation of ventral pallidum is sufficient to cause reward and motivation enhancements, and (3) activation patterns in ventral pallidum neurons specifically encode reward and motivation signals via phasic bursts of excitation to incentive and hedonic stimuli. We conclude that the ventral pallidum may serve as an important 'limbic final common pathway' for mesocorticolimbic processing of many rewards.

Quantitative MRI in refractory temporal lobe epilepsy: relationship with surgical outcomes

PubMed Central

Bonilha, Leonardo

2015-01-01

Medically intractable temporal lobe epilepsy (TLE) remains a serious health problem. Across treatment centers, up to 40% of patients with TLE will continue to experience persistent postoperative seizures at 2-year follow-up. It is unknown why such a large number of patients continue to experience seizures despite being suitable candidates for resective surgery. Preoperative quantitative MRI techniques may provide useful information on why some patients continue to experience disabling seizures, and may have the potential to develop prognostic markers of surgical outcome. In this article, we provide an overview of how quantitative MRI morphometric and diffusion tensor imaging (DTI) data have improved the understanding of brain structural alterations in patients with refractory TLE. We subsequently review the studies that have applied quantitative structural imaging techniques to identify the neuroanatomical factors that are most strongly related to a poor postoperative prognosis. In summary, quantitative imaging studies strongly suggest that TLE is a disorder affecting a network of neurobiological systems, characterized by multiple and inter-related limbic and extra-limbic network abnormalities. The relationship between brain alterations and postoperative outcome are less consistent, but there is emerging evidence suggesting that seizures are less likely to remit with surgery when presurgical abnormalities are observed in the connectivity supporting brain regions serving as network nodes located outside the resected temporal lobe. Future work, possibly harnessing the potential from multimodal imaging approaches, may further elucidate the etiology of persistent postoperative seizures in patients with refractory TLE. Furthermore, quantitative imaging techniques may be explored to provide individualized measures of postoperative seizure freedom outcome. PMID:25853080

Size Matters: Increased Grey Matter in Boys with Conduct Problems and Callous-Unemotional Traits

ERIC Educational Resources Information Center

De Brito, Stephane A.; Mechelli, Andrea; Wilke, Marko; Laurens, Kristin R.; Jones, Alice P.; Barker, Gareth J.; Hodgins, Sheilagh; Viding, Essi

2009-01-01

Brain imaging studies of adults with psychopathy have identified structural and functional abnormalities in limbic and prefrontal regions that are involved in emotion recognition, decision-making, morality and empathy. Among children with conduct problems, a small subgroup presents callous-unemotional traits thought to be antecedents of…

Cortical functional connectivity decodes subconscious, task-irrelevant threat-related emotion processing

PubMed Central

Pantazatos, Spiro P.; Talati, Ardesheer; Pavlidis, Paul; Hirsch, Joy

2012-01-01

It is currently unclear to what extent cortical structures are required for and engaged during subconscious processing of biologically salient affective stimuli (i.e. the ‘low-road’ vs. ‘many-roads’ hypotheses). Here we show that cortical-cortical and cortical-subcortical functional connectivity (FC) contain substantially more information, relative to subcortical-subcortical FC (i.e. ‘subcortical alarm’ and other limbic regions), that predicts subliminal fearful face processing within individuals using training data from separate subjects. A plot of classification accuracy vs. number of selected whole-brain FC features revealed 92% accuracy when learning was based on the top 8 features from each training set. The most informative FC was between right amygdala and precuneus, which increased during subliminal fear conditions, while left and right amygdala FC decreased, suggesting a bilateral decoupling of this key limbic region during processing of subliminal fear-related stimuli. Other informative FC included angular gyrus, middle temporal gyrus and cerebellum. These findings identify FC that decodes subliminally perceived, task-irrelevant affective stimuli, and suggest that cortical structures are actively engaged by and appear to be essential for subliminal fear processing. PMID:22484206

Cortical functional connectivity decodes subconscious, task-irrelevant threat-related emotion processing.

PubMed

Pantazatos, Spiro P; Talati, Ardesheer; Pavlidis, Paul; Hirsch, Joy

2012-07-16

It is currently unclear to what extent cortical structures are required for and engaged during subconscious processing of biologically salient affective stimuli (i.e. the 'low-road' vs. 'many-roads' hypotheses). Here we show that cortical-cortical and cortical-subcortical functional connectivity (FC) contain substantially more information, relative to subcortical-subcortical FC (i.e. 'subcortical alarm' and other limbic regions), that predicts subliminal fearful face processing within individuals using training data from separate subjects. A plot of classification accuracy vs. number of selected whole-brain FC features revealed 92% accuracy when learning was based on the top 8 features from each training set. The most informative FC was between right amygdala and precuneus, which increased during subliminal fear conditions, while left and right amygdala FC decreased, suggesting a bilateral decoupling of this key limbic region during processing of subliminal fear-related stimuli. Other informative FC included angular gyrus, middle temporal gyrus and cerebellum. These findings identify FC that decodes subliminally perceived, task-irrelevant affective stimuli, and suggest that cortical structures are actively engaged by and appear to be essential for subliminal fear processing. Published by Elsevier Inc.

Relationship between body mass index and hippocampal glutamate/glutamine in bipolar disorder.

PubMed

Bond, David J; da Silveira, Leonardo Evangelista; MacMillan, Erin L; Torres, Ivan J; Lang, Donna J; Su, Wayne; Honer, William G; Lam, Raymond W; Yatham, Lakshmi N

2016-02-01

We previously reported that patients with early-stage bipolar disorder, but not healthy comparison controls, had body mass index (BMI)-related volume reductions in limbic brain areas, suggesting that the structural brain changes characteristic of bipolar disorder were more pronounced with increased weight. To determine whether the most consistently reported neurochemical abnormality in bipolar disorder, increased glutamate/glutamine (Glx), was also more prominent with higher BMI. We used single-voxel proton magnetic resonance spectroscopy to measure hippocampal Glx in 51 patients with first-episode mania (mean BMI = 24.1) and 28 healthy controls (mean BMI = 23.3). In patients, but not healthy controls, linear regression demonstrated that higher BMI predicted greater Glx. Factorial ANCOVA showed a significant BMI × diagnosis interaction, confirming a distinct effect of weight on Glx in patients. Together with our volumetric studies, these results suggest that higher BMI is associated with more pronounced structural and neurochemical limbic brain changes in bipolar disorder, even in early-stage patients with low obesity rates. © The Royal College of Psychiatrists 2016.

Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei.

PubMed

Feng, Li; Motelow, Joshua E; Ma, Chanthia; Biche, William; McCafferty, Cian; Smith, Nicholas; Liu, Mengran; Zhan, Qiong; Jia, Ruonan; Xiao, Bo; Duque, Alvaro; Blumenfeld, Hal

2017-11-22

The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function. SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal maintenance, but its precise seizure-associated functions are not known. We recorded neuronal activity in three different thalamic regions and found divergent activity patterns, which may respectively participate in seizure propagation, impaired level of conscious arousal, and altered relay of information to the cortex during focal limbic seizures. These very different activity patterns within the thalamus may help explain why focal temporal lobe seizures often disrupt widespread network function, and can help guide future treatments aimed at restoring normal thalamocortical network activity and cognition. Copyright © 2017 the authors 0270-6474/17/3711441-14$15.00/0.

Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei

PubMed Central

Feng, Li; Motelow, Joshua E.; Ma, Chanthia; Liu, Mengran; Zhan, Qiong; Jia, Ruonan; Xiao, Bo; Duque, Alvaro

2017-01-01

The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function. SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal maintenance, but its precise seizure-associated functions are not known. We recorded neuronal activity in three different thalamic regions and found divergent activity patterns, which may respectively participate in seizure propagation, impaired level of conscious arousal, and altered relay of information to the cortex during focal limbic seizures. These very different activity patterns within the thalamus may help explain why focal temporal lobe seizures often disrupt widespread network function, and can help guide future treatments aimed at restoring normal thalamocortical network activity and cognition. PMID:29066556

[Oxidative metabolism of main and accessory olfactory bulbs, limpic system and hypothalamus during the estral cycle of the rat (author's transl)].

PubMed

Sánchez-Criado, J E

1979-06-01

The in vitro oxidative metabolism of hypothalamus, olfactory and limbic systems from female rats in the estrous cycle have been measured. The accessory olfactory bulb becomes most active during diestrous when the hypothalamus reaches its lowest values.

The Role of the Limbic System in Human Communication.

ERIC Educational Resources Information Center

Lamendella, John T.

Linguistics has chosen as its niche the language component of human communication and, naturally enough, the neurolinguist has concentrated on lateralized language systems of the cerebral hemispheres. However, decoding a speaker's total message requires attention to gestures, facial expressions, and prosodic features, as well as other somatic and…

Neurogenic Communication Disorders and Paralleling Agraphic Disturbances: Implications for Concerns in Basic Writing.

ERIC Educational Resources Information Center

De Jarnette, Glenda

Vertical and lateral integration are two important nervous system integrations that affect the development of oral behaviors. There are three progressions in the vertical integration process for speech nervous system development: R-complex speech (ritualistic, memorized expressions), limbic speech (emotional expressions), and cortical speech…

Neuroanatomical abnormalities in chronic tinnitus in the human brain

PubMed Central

Adjamian, Peyman; Hall, Deborah A.; Palmer, Alan R.; Allan, Thomas W.; Langers, Dave R.M.

2014-01-01

In this paper, we review studies that have investigated brain morphology in chronic tinnitus in order to better understand the underlying pathophysiology of the disorder. Current consensus is that tinnitus is a disorder involving a distributed network of peripheral and central pathways in the nervous system. However, the precise mechanism remains elusive and it is unclear which structures are involved. Given that brain structure and function are highly related, identification of anatomical differences may shed light upon the mechanism of tinnitus generation and maintenance. We discuss anatomical changes in the auditory cortex, the limbic system, and prefrontal cortex, among others. Specifically, we discuss the gating mechanism of tinnitus and evaluate the evidence in support of the model from studies of brain anatomy. Although individual studies claim significant effects related to tinnitus, outcomes are divergent and even contradictory across studies. Moreover, results are often confounded by the presence of hearing loss. We conclude that, at present, the overall evidence for structural abnormalities specifically related to tinnitus is poor. As this area of research is expanding, we identify some key considerations for research design and propose strategies for future research. PMID:24892904

Limbic control of aggression in the cat.

PubMed

Adamec, R E; Stark-Adamec, C I

1983-01-01

Over a decade of work by Flynn and colleagues has delineated a network of limbic circuits which function to modulate the expression of predatory aggression and defence in the cat, and aspects of this work are reviewed. In particular, Flynn's work revealed a circuit involving the basomedial amygdala which functions to suppress attack, and at the same time facilitates defence. A second circuit, involving the ventral hippocampus, is involved in attack facilitation. Studies relating stable differences in excitability in these two circuits to developmentally determined behavioural dispositions toward aggression or defence are summarized. Finally, the impact of experimentally induced limbic seizures on interictally maintained expression of aggression and defence behaviourally, and on limbic excitability are reviewed. Taken together, the data indicate that the behavioural balance of attack and defence is under the tonic control of opponent limbic circuits, which are themselves biased in a measureable manner. Developmental studies indicate that adult defensiveness is determined early in life, so early as to suggest some pre-programmed neuro-developmental process. Experimentally induced seizures alter behaviour lastingly, producing an increase in defensive disposition. At the same time there is an equally lasting potentiation of interictal transmission of neural activity from the amygdala to the hypothalamus. Moreover, seizures may reduce interictal transmission of activity through the ventral hippocampus by potentiating recurrent inhibition. These effects of seizures are of interest since seizures reproduce naturally occurring differences in limbic excitability seen in naturally defensive cats.

Independent Epileptiform Discharge Patterns in the Olfactory and Limbic Areas of the In Vitro Isolated Guinea Pig Brain During 4-Aminopyridine Treatment

PubMed Central

Carriero, Giovanni; Uva, Laura; Gnatkovsky, Vadym; Avoli, Massimo; de Curtis, Marco

2016-01-01

In vitro studies performed on brain slices demonstrate that the potassium channel blocker 4-aminopyridine (4AP, 50 μM) discloses electrographic seizure activity and interictal discharges. These epileptiform patterns have been further analyzed here in a isolated whole guinea pig brain in vitro by using field potential recordings in olfactory and limbic structures. In 8 of 13 experiments runs of fast oscillatory activity (fast runs, FRs) in the piriform cortex (PC) propagated to the lateral entorhinal cortex (EC), hippocampus and occasionally to the medial EC. Early and late FRs were asynchronous in the hemispheres showed different duration [1.78 ± 0.51 and 27.95 ± 4.55 (SD) s, respectively], frequency of occurrence (1.82 ± 0.49 and 34.16 ± 6.03 s) and frequency content (20–40 vs. 40–60 Hz). Preictal spikes independent from the FRs appeared in the hippocampus/EC and developed into ictal-like discharges that did not propagate to the PC. Ictal-like activity consisted of fast activity with onset either in the hippocampus (n = 6) or in the mEC (n = 2), followed by irregular spiking and sequences of diffusely synchronous bursts. Perfusion of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid (100 μM) did not prevent FRs, increased the duration of limbic ictal-like discharges and favored their propagation to olfactory structures. The AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (50 μM) blocked ictal-like events and reduced FRs. In conclusion, 4AP-induced epileptiform activities are asynchronous and independent in olfactory and hippocampal-entorhinal regions. Epileptiform discharges in the isolated guinea pig brain show different pharmacological properties compared with rodent in vitro slices. PMID:20220076

Modulating Emotional Experience Using Electrical Stimulation of the Medial-Prefrontal Cortex: A Preliminary tDCS-fMRI Study.

PubMed

Abend, Rany; Sar-El, Roy; Gonen, Tal; Jalon, Itamar; Vaisvaser, Sharon; Bar-Haim, Yair; Hendler, Talma

2018-05-09

Implicit regulation of emotions involves medial-prefrontal cortex (mPFC) regions exerting regulatory control over limbic structures. Diminished regulation relates to aberrant mPFC functionality and psychopathology. Establishing means of modulating mPFC functionality could benefit research on emotion and its dysregulation. Here, we tested the capacity of transcranial direct current stimulation (tDCS) targeting mPFC to modulate subjective emotional states by facilitating implicit emotion regulation. Stimulation was applied concurrently with functional magnetic resonance imaging to validate its neurobehavioral effect. Sixteen participants were each scanned twice, counterbalancing active and sham tDCS application, while undergoing negative mood induction (clips featuring negative vs. neutral contents). Effects of stimulation on emotional experience were assessed using subjective and neural measures. Subjectively, active stimulation led to significant reduction in reported intensity of experienced emotions to negatively valenced (p = 0.005) clips but not to neutral clips (p > 0.99). Active stimulation further mitigated a rise in stress levels from pre- to post-induction (sham: p = 0.004; active: p = 0.15). Neurally, stimulation increased activation in mPFC regions associated with implicit emotion regulation (ventromedial-prefrontal cortex; subgenual anterior-cingulate cortex, sgACC), and in ventral striatum, a core limbic structure (all ps < 0.05). Stimulation also altered functional connectivity (assessed using whole-brain psycho-physiological interaction) between these regions, and with additional limbic regions. Stimulation-induced sgACC activation correlated with reported emotion intensity and depressive symptoms (rs > 0.64, ps < 0.018), suggesting individual differences in stimulation responsivity. Results of this study indicate the potential capacity of tDCS to facilitate brain activation in mPFC regions underlying implicit regulation of emotion and accordingly modulate subjective emotional experiences. © 2018 International Neuromodulation Society.

Loss of Autonoetic Awareness of Recent Autobiographical Episodes and Accelerated Long-Term Forgetting in a Patient with Previously Unrecognized Glutamic Acid Decarboxylase Antibody Related Limbic Encephalitis.

PubMed

Witt, Juri-Alexander; Vogt, Viola Lara; Widman, Guido; Langen, Karl-Josef; Elger, Christian Erich; Helmstaedter, Christoph

2015-01-01

We describe a 35-year-old male patient presenting with depressed mood and emotional instability, who complained about severe anterograde and retrograde memory deficits characterized by accelerated long-term forgetting and loss of autonoetic awareness regarding autobiographical memories of the last 3 years. Months before he had experienced two breakdowns of unknown etiology giving rise to the differential diagnosis of epileptic seizures after various practitioners and clinics had suggested different etiologies such as a psychosomatic condition, burnout, depression, or dissociative amnesia. Neuropsychological assessment indicated selectively impaired figural memory performance. Extended diagnostics confirmed accelerated forgetting of previously learned and retrievable verbal material. Structural imaging showed bilateral swelling and signal alterations of temporomesial structures (left >right). Video-EEG monitoring revealed a left temporal epileptic focus and subclincal seizure, but no overt seizures. Antibody tests in serum and liquor were positive for glutamic acid decarboxylase antibodies. These findings led to the diagnosis of glutamic acid decarboxylase antibody related limbic encephalitis. Monthly steroid pulses over 6 months led to recovery of subjective memory and to intermediate improvement but subsequent worsening of objective memory performance. During the course of treatment, the patient reported de novo paroxysmal non-responsive states. Thus, antiepileptic treatment was started and the patient finally became seizure free. At the last visit, vocational reintegration was successfully in progress. In conclusion, amygdala swelling, retrograde biographic memory impairment, accelerated long-term forgetting, and emotional instability may serve as indicators of limbic encephalitis, even in the absence of overt epileptic seizures. The monitoring of such patients calls for a standardized and concerted multilevel diagnostic approach with repeated assessments.

[Anti-Ma2-associated encephalitis and paraneoplastic limbic encephalitis].

PubMed

Yamamoto, Tomotaka; Tsuji, Shoji

2010-08-01

Anti-Ma2-associated encephalitis (or anti-Ma2 encephalitis) is a paraneoplastic neurological syndrome (PNS) characterized by isolated or combined limbic, diencephalic, or brainstem dysfunction. Anti-Ma2 antibodies detected in the serum or cerebrospinal fluid of patients are highly specific for this disease entity and belong to a group of well-characterized onconeuronal antibodies (or classical antibodies). The corresponding antigen, Ma2 is selectively expressed intracellularly in neurons and tumors as is the case with other onconeuronal antigens targeted by classical antibodies. However, in most cases the clinical pictures are different from those of classical PNS and this creates a potential risk of underdiagnosis. Although limbic dysfunction is the most common manifestation in patients with anti-Ma2 encephalitis which is one of the major causes of paraneoplastic limbic encephalitis (LE), it has been reported that less than 30% of the patients with anti-Ma2 LE exhibit clinical presentations typical of the classical description of LE. Of the remaining, many exhibit excessive daytime sleepiness, vertical ophthalmoparesis, or both associated with LE, because of frequent involvement of the diencephalon and/or upper brainstem. Anti-Ma2 LE can also be manifested as a pure psychiatric disturbance such as obsessive-compulsive disorder in a few cases. Some patients develop mesodiencephalic encephalitis with minor involvement of the limbic system, and some may manifest severe hypokinesis. About 40% of the patients with anti-Ma2 antibodies also have antibodies against different epitopes on Ma1, a homologue of Ma2. These patients may have predominant cerebellar and/or brainstem dysfunctions due to more extensive involvement of subtentorial structures. Anti-Ma2 encephalitis is outstanding among other PNS associated with classical antibodies in that the response rate to treatment is relatively high. While it can cause severe neurological deficits or death in a substantial proportion of the patients, approximately one-third show neurological improvement and another 20 - 40% stabilize in response to treatment, including immunotherapy and/or tumor treatment. Patients who have limited CNS involvement and testicular tumors with complete response to therapy are more likely to show neurological improvement. This fact emphasizes the importance of early diagnosis and prompt initiation of therapy. However, it should be noted that even carcinoma in situ, which is difficult to detect can cause severe neurological disorders. In this respect, it is useful to highlight that anti-Ma2 encephalitis is almost always associated with testicular germ cell tumors in men younger than 50 years. We experienced a 40-year-old patient with severe hypokinesis caused by anti-Ma2 encephalitis associated with bilateral intratubular germ-cell neoplasm of the testes. In older men and women, non-small-cell lung cancer is most common but various types of cancers are reported to be associated. In this study,in addition to reviewing the above case we have reviewed the significance of anti-Ma2 antibodies in the diagnosis of anti-Ma2 encephalitis and the clinical features of this disease.

Psychosis: Atypical Limbic Epilepsy versus Limbic Hyperexcitability with Onset at Puberty?

PubMed Central

Sharp, Frank R.; Hendren, Robert L.

2009-01-01

Phencyclidine (PCP), Ketamine (Special K) and MK-801 are non-competitive NMDA antagonists that produce acute psychosis in humans. The psychosis produced by these psychomimetic drugs is indistinguishable from schizophrenia and includes both positive and negative symptoms. This drug-induced psychosis occurs after puberty in humans. This brief review argues that this psychosis is an atypical form of limbic epilepsy based upon MK-801 induced spike-and-wave activity in rats and based upon increased blood flow and metabolism in brain of patients with psychosis caused by these psychomimetics. Moreover, there is a specific limbic thalamcortical psychosis circuit that mediates cell injury in limbic cortex of rodents and may mediate this PCP-induced psychosis in humans. It is proposed that this thalamocortical psychosis circuit develops at puberty and can mediate psychosis at puberty and in adulthood by PCP and ketamine-induced psychosis, and possibly in schizophrenia, bipolar disease and other psychotic states. Finally, based upon this developmentally regulated psychosis-epilepsy related thalamocortical circuitry, it is proposed that anti-epileptic drugs that promote GABAergic mechanisms might decrease the probability of episodic psychosis from any cause. PMID:17416210

Methylphenidate and Atomoxetine Inhibit Social Play Behavior through Prefrontal and Subcortical Limbic Mechanisms in Rats

PubMed Central

Achterberg, E.J. Marijke; van Kerkhof, Linda W.M.; Damsteegt, Ruth; Trezza, Viviana

2015-01-01

Positive social interactions during the juvenile and adolescent phases of life, in the form of social play behavior, are important for social and cognitive development. However, the neural mechanisms of social play behavior remain incompletely understood. We have previously shown that methylphenidate and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), suppress social play in rats through a noradrenergic mechanism of action. Here, we aimed to identify the neural substrates of the play-suppressant effects of these drugs. Methylphenidate is thought to exert its effects on cognition and emotion through limbic corticostriatal systems. Therefore, methylphenidate was infused into prefrontal and orbitofrontal cortical regions as well as into several subcortical limbic areas implicated in social play. Infusion of methylphenidate into the anterior cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula inhibited social play, but not social exploratory behavior or locomotor activity. Consistent with a noradrenergic mechanism of action of methylphenidate, infusion of the noradrenaline reuptake inhibitor atomoxetine into these same regions also reduced social play. Methylphenidate administration into the prelimbic, medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal thalamus, or nucleus accumbens shell was ineffective. Our data show that the inhibitory effects of methylphenidate and atomoxetine on social play are mediated through a distributed network of prefrontal and limbic subcortical regions implicated in cognitive control and emotional processes. These findings increase our understanding of the neural underpinnings of this developmentally important social behavior, as well as the mechanism of action of two widely used treatments for ADHD. PMID:25568111

Neuronal Activation in the Central Nervous System of Rats in the Initial Stage of Chronic Kidney Disease-Modulatory Effects of Losartan and Moxonidine

PubMed Central

Palkovits, Miklós; Šebeková, Katarína; Klenovics, Kristina Simon; Kebis, Anton; Fazeli, Gholamreza; Bahner, Udo; Heidland, August

2013-01-01

The effect of mild chronic renal failure (CRF) induced by 4/6-nephrectomy (4/6NX) on central neuronal activations was investigated by c-Fos immunohistochemistry staining and compared to sham-operated rats. In the 4/6 NX rats also the effect of the angiotensin receptor blocker, losartan, and the central sympatholyticum moxonidine was studied for two months. In serial brain sections Fos-immunoreactive neurons were localized and classified semiquantitatively. In 37 brain areas/nuclei several neurons with different functional properties were strongly affected in 4/6NX. It elicited a moderate to high Fos-activity in areas responsible for the monoaminergic innervation of the cerebral cortex, the limbic system, the thalamus and hypothalamus (e.g. noradrenergic neurons of the locus coeruleus, serotonergic neurons in dorsal raphe, histaminergic neurons in the tuberomamillary nucleus). Other monoaminergic cell groups (A5 noradrenaline, C1 adrenaline, medullary raphe serotonin neurons) and neurons in the hypothalamic paraventricular nucleus (innervating the sympathetic preganglionic neurons and affecting the peripheral sympathetic outflow) did not show Fos-activity. Stress- and pain-sensitive cortical/subcortical areas, neurons in the limbic system, the hypothalamus and the circumventricular organs were also affected by 4/6NX. Administration of losartan and more strongly moxonidine modulated most effects and particularly inhibited Fos-activity in locus coeruleus neurons. In conclusion, 4/6NX elicits high activity in central sympathetic, stress- and pain-related brain areas as well as in the limbic system, which can be ameliorated by losartan and particularly by moxonidine. These changes indicate a high sensitivity of CNS in initial stages of CKD which could be causative in clinical disturbances. PMID:23818940

Ventral Pallidum Roles in Reward and Motivation

PubMed Central

Smith, Kyle S.; Tindell, Amy J.; Aldridge, J. Wayne; Berridge, Kent C.

2008-01-01

In recent years the ventral pallidum has become a focus of great research interest as a mechanism of reward and incentive motivation. As a major output for limbic signals, the ventral pallidum was once associated primarily with motor functions rather than regarded as a reward structure in its own right. However, ample evidence now suggests that ventral pallidum function is a major mechanism of reward in the brain. We review data indicating that 1) an intact ventral pallidum is necessary for normal reward and motivation, 2) stimulated activation of ventral pallidum is sufficient to cause reward and motivation enhancements, and 3) activation patterns in ventral pallidum neurons specifically encode reward and motivation signals via phasic bursts of excitation to incentive and hedonic stimuli. We conclude that the ventral pallidum may serve as an important ‘limbic final common pathway’ for mesocorticolimbic processing of many rewards. PMID:18955088

Associative processes in addiction and reward. The role of amygdala-ventral striatal subsystems.

PubMed

Everitt, B J; Parkinson, J A; Olmstead, M C; Arroyo, M; Robledo, P; Robbins, T W

1999-06-29

Only recently have the functional implications of the organization of the ventral striatum, amygdala, and related limbic-cortical structures, and their neuroanatomical interactions begun to be clarified. Processes of activation and reward have long been associated with the NAcc and its dopamine innervation, but the precise relationships between these constructs have remained elusive. We have sought to enrich our understanding of the special role of the ventral striatum in coordinating the contribution of different functional subsystems to confer flexibility, as well as coherence and vigor, to goal-directed behavior, through different forms of associative learning. Such appetitive behavior comprises many subcomponents, some of which we have isolated in these experiments to reveal that, not surprisingly, the mechanisms by which an animal sequences responding to reach a goal are complex. The data reveal how the different components, pavlovian approach (or sign-tracking), conditioned reinforcement (whereby pavlovian stimuli control goal-directed action), and also more general response-invigorating processes (often called "activation," "stress," or "drive") may be integrated within the ventral striatum through convergent interactions of the amygdala, other limbic cortical structures, and the mesolimbic dopamine system to produce coherent behavior. The position is probably not far different when considering aversively motivated behavior. Although it may be necessary to employ simplified, even abstract, paradigms for isolating these mechanisms, their concerted action can readily be appreciated in an adaptive, functional setting, such as the responding by rats for intravenous cocaine under a second-order schedule of reinforcement. Here, the interactions of primary reinforcement, psychomotor activation, pavlovian conditioning, and the control that drug cues exert over the integrated drug-seeking response can be seen to operate both serially and concurrently. The power of our analytic techniques for understanding complex motivated behavior has been evident for some time. However, the crucial point is that we are now able to map these components with increasing certainty onto discrete amygdaloid, and other limbic cortical-ventral striatal subsystems. The neural dissection of these mechanisms also serves an important theoretical purpose in helping to validate the various hypothetical constructs and further developing theory. Major challenges remain, not the least of which is an understanding of the operation of the ventral striatum together with its dopaminergic innervation and its interactions with the basolateral amygdala, hippocampal formation, and prefrontal cortex at a more mechanistic, neuronal level.

Intergenerational neural mediators of early-life anxious temperament.

PubMed

Fox, Andrew S; Oler, Jonathan A; Shackman, Alexander J; Shelton, Steven E; Raveendran, Muthuswamy; McKay, D Reese; Converse, Alexander K; Alexander, Andrew; Davidson, Richard J; Blangero, John; Rogers, Jeffrey; Kalin, Ned H

2015-07-21

Understanding the heritability of neural systems linked to psychopathology is not sufficient to implicate them as intergenerational neural mediators. By closely examining how individual differences in neural phenotypes and psychopathology cosegregate as they fall through the family tree, we can identify the brain systems that underlie the parent-to-child transmission of psychopathology. Although research has identified genes and neural circuits that contribute to the risk of developing anxiety and depression, the specific neural systems that mediate the inborn risk for these debilitating disorders remain unknown. In a sample of 592 young rhesus monkeys that are part of an extended multigenerational pedigree, we demonstrate that metabolism within a tripartite prefrontal-limbic-midbrain circuit mediates some of the inborn risk for developing anxiety and depression. Importantly, although brain volume is highly heritable early in life, it is brain metabolism-not brain structure-that is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.

A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction.

PubMed

Kiehl, Kent A

2006-06-15

Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes associated with focal brain lesions or insults and results from psychophysiology, cognitive psychology and cognitive and affective neuroscience in health and psychopathy. The review illustrates that the brain regions implicated in psychopathy include the orbital frontal cortex, insula, anterior and posterior cingulate, amygdala, parahippocampal gyrus, and anterior superior temporal gyrus. The relevant functional neuroanatomy of psychopathy thus includes limbic and paralimbic structures that may be collectively termed 'the paralimbic system'. The paralimbic system dysfunction model of psychopathy is discussed as it relates to the extant literature on psychopathy.

Gut vagal afferents differentially modulate innate anxiety and learned fear.

PubMed

Klarer, Melanie; Arnold, Myrtha; Günther, Lydia; Winter, Christine; Langhans, Wolfgang; Meyer, Urs

2014-05-21

Vagal afferents are an important neuronal component of the gut-brain axis allowing bottom-up information flow from the viscera to the CNS. In addition to its role in ingestive behavior, vagal afferent signaling has been implicated modulating mood and affect, including distinct forms of anxiety and fear. Here, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on innate anxiety, conditioned fear, and neurochemical parameters in the limbic system. We found that compared with Sham controls, SDA rats consistently displayed reduced innate anxiety-like behavior in three procedures commonly used in preclinical rodent models of anxiety, namely the elevated plus maze test, open field test, and food neophobia test. On the other hand, SDA rats exhibited increased expression of auditory-cued fear conditioning, which specifically emerged as attenuated extinction of conditioned fear during the tone re-exposure test. The behavioral manifestations in SDA rats were associated with region-dependent changes in noradrenaline and GABA levels in key areas of the limbic system, but not with functional alterations in the hypothalamus-pituitary-adrenal grand stress. Our study demonstrates that innate anxiety and learned fear are both subjected to visceral modulation through abdominal vagal afferents, possibly via changing limbic neurotransmitter systems. These data add further weight to theories emphasizing an important role of afferent visceral signals in the regulation of emotional behavior. Copyright © 2014 the authors 0270-6474/14/347067-10$15.00/0.

A Longitudinal Mapping Study on Cortical Plasticity of Peripheral Nerve Injury Treated by Direct Anastomosis and Electroacupuncture in Rats.

PubMed

Wu, Jia-Jia; Lu, Ye-Chen; Hua, Xu-Yun; Ma, Shu-Jie; Xu, Jian-Guang

2018-06-01

We used functional magnetic resonance imaging to provide a longitudinal description of cortical plasticity caused by electroacupuncture (EA) of sciatic nerve transection and direct anastomosis in rats. Sixteen rats in a sciatic nerve transection and direct anastomosis model were randomly divided into intervention and control groups. EA intervention in the position of ST-36, GB-30 was conducted continuously for 4 months in the intervention group. Functional magnetic resonance imaging and gait assessment were performed every month after intervention. The somatosensory area was more activated in the first 2 months and then deactivated in the rest 2 months when EA was applied. The pain-related areas had the same activation pattern as the somatosensory area. The limbic/paralimbic areas fluctuated more during the EA intervention, which was not constantly activated or deactivated as previous studies reported. We attributed such changes in somatosensory and pain-related areas to the gradual reduction of sensory afferentation. The alterations in limbic/paralimbic system might be associated with the confrontation between the upregulating effect of paresthesia or pain and the downregulating effect of EA intervention through the autonomic nerve system. The gait analysis showed significantly higher maximum contact mean intensity in the intervention group. The alterations in the brain brought about by the long-term therapeutic effect of EA could be described as a synchronized activation pattern in the somatosensory and pain-related areas and a fluctuating pattern in the limbic/paralimbic system. Copyright © 2018 Elsevier Inc. All rights reserved.

Paraneoplastic limbic encephalitis in a patient with extragonadal choriocarcinoma--significance of onconeural antibodies.

PubMed

Szkandera, Joanna; Ploner, Ferdin; Bauernhofer, Thomas; Kasparek, Anne-Katrin; Payer, Franz; Balic, Marija; Knechtel, Gudrun; Gerger, Armin; Gallè, Günter; Samonigg, Hellmut; Hofmann, Günter

2010-01-01

Paraneoplastic limbic or brainstem encephalitis is considered to be an autoimmune-mediated disorder of the nervous system associated with different types of cancer including germ cell tumors. We report on a 31-year-old patient presenting with eye motility dysfunction, dysarthrophonia, lethargy, depression, slow mentation, disorientation, dysgraphia, and retarded motion sequence. Neurologic tests, brain imaging, and blood chemistry tests failed to determine the cause of the symptoms. Further examinations including ultrasound of the abdomen led to the detection of a retroperitoneal mass. The biopsy of this mass showed fractions of a choriocarcinoma. The patient underwent curative chemotherapy, but although the cancer therapy was successful, the neurologic disorders did not improve. Concurrent examination for anti-Ma2 antibodies in the serum was positive and confirmed the paraneoplastic origin of these symptoms. Patients with symptoms of limbic or brainstem encephalitis, especially young men, should be tested for anti-Ma2 antibodies in the serum to elucidate their origin. The detection of these antibodies supports the diagnosis of a paraneoplastic syndrome, and may lead to the earlier identification of an otherwise hidden extragonadal germ cell tumor. Copyright © 2010 S. Karger AG, Basel.

Decreased gray matter volume in the left hippocampus and bilateral calcarine cortex in coal mine flood disaster survivors with recent onset PTSD.

PubMed

Zhang, Jian; Tan, Qingrong; Yin, Hong; Zhang, Xiaoliang; Huan, Yi; Tang, Lihua; Wang, Huaihai; Xu, Junqing; Li, Lingjiang

2011-05-31

Although limbic structure changes have been found in chronic and recent onset post-traumatic stress disorder (PTSD) patients, there are few studies about brain structure changes in recent onset PTSD patients after a single extreme and prolonged trauma. In the current study, 20 coal mine flood disaster survivors underwent magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) and region of interest (ROI) techniques were used to detect the gray matter and white matter volume changes in 10 survivors with recent onset PTSD and 10 survivors without PTSD. The correlation between the Clinician-Administered PTSD Scale (CAPS) and gray matter density in the ROI was also studied. Compared with survivors without PTSD, survivors with PTSD had significantly decreased gray matter volume and density in left anterior hippocampus, left parahippocampal gyrus, and bilateral calcarine cortex. The CAPS score correlated negatively with the gray matter density in bilateral calcarine cortex and left hippocampus in coal mine disaster survivors. Our study suggests that the gray matter volume and density of limbic structure decreased in recent onset PTSD patients who were exposed to extreme trauma. PTSD symptom severity was associated with gray matter density in calcarine cortex and hippocampus. 2010 Elsevier Ireland Ltd. All rights reserved.

Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction.

PubMed

Chen, Jianhuai; Chen, Yun; Gao, Qingqiang; Chen, Guotao; Dai, Yutian; Yao, Zhijian; Lu, Qing

2018-05-01

Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear. Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis. Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale. These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.

Diminished fronto-limbic functional connectivity in child sexual offenders.

PubMed

Kneer, Jonas; Borchardt, Viola; Kärgel, Christian; Sinke, Christopher; Massau, Claudia; Tenbergen, Gilian; Ponseti, Jorge; Walter, Henrik; Beier, Klaus M; Schiffer, Boris; Schiltz, Kolja; Walter, Martin; Kruger, Tillmann H C

2018-02-22

Child sexual abuse and neglect have been related to an increased risk for the development of a wide range of behavioral, psychological, and sexual problems and increased rates of suicidal behavior. Contrary to the large amount of research focusing on the negative mental health consequences of child sexual abuse, very little is known about the characteristics of child sexual offenders and the neuronal underpinnings contributing to child sexual offending. This study investigates differences in resting state functional connectivity (rs-FC) between non-pedophilic child sexual offenders (N = 20; CSO-P) and matched healthy controls (N = 20; HC) using a seed-based approach. The focus of this investigation of rs-FC in CSO-P was put on prefrontal and limbic regions highly relevant for emotional and behavioral processing. Results revealed a significant reduction of rs-FC between the right centromedial amygdala and the left dorsolateral prefrontal cortex in child sexual offenders compared to controls. Given that, in the healthy brain, there is a strong top-down inhibitory control of prefrontal over limbic structures, these results suggest that diminished rs-FC between the amygdala and the dorsolateral prefrontal cortex and may foster sexual deviance and sexual offending. A profound understanding of these concepts should contribute to a better understanding of the occurrence of child sexual offending, as well as further development of more differentiated and effective interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional topography of serotonergic systems supports the Deakin/Graeff hypothesis of anxiety and affective disorders.

PubMed

Paul, Evan D; Lowry, Christopher A

2013-12-01

Over 20 years ago, Deakin and Graeff hypothesized about the role of different serotonergic pathways in controlling the behavioral and physiologic responses to aversive stimuli, and how compromise of these pathways could lead to specific symptoms of anxiety and affective disorders. A growing body of evidence suggests these serotonergic pathways arise from topographically organized subpopulations of serotonergic neurons located in the dorsal and median raphe nuclei. We argue that serotonergic neurons in the dorsal/caudal parts of the dorsal raphe nucleus project to forebrain limbic regions involved in stress/conflict anxiety-related processes, which may be relevant for anxiety and affective disorders. Serotonergic neurons in the "lateral wings" of the dorsal raphe nucleus provide inhibitory control over structures controlling fight-or-flight responses. Dysfunction of this pathway could be relevant for panic disorder. Finally, serotonergic neurons in the median raphe nucleus, and the developmentally and functionally-related interfascicular part of the dorsal raphe nucleus, give rise to forebrain limbic projections that are involved in tolerance and coping with aversive stimuli, which could be important for affective disorders like depression. Elucidating the mechanisms through which stress activates these topographically and functionally distinct serotonergic pathways, and how dysfunction of these pathways leads to symptoms of neuropsychiatric disorders, may lead to the development of novel approaches to both the prevention and treatment of anxiety and affective disorders.

Reduced limbic and hypothalamic volumes correlate with bone density in early Alzheimer's disease.

PubMed

Loskutova, Natalia; Honea, Robyn A; Brooks, William M; Burns, Jeffrey M

2010-01-01

Accelerated bone loss is associated with Alzheimer's disease (AD). Although the central nervous system plays a direct role in regulating bone mass, primarily through the actions of the hypothalamus, there is little work investigating the possible role of neurodegeneration in bone loss. In this cross-sectional study, we examined the association between bone mineral density (BMD) and neuroimaging markers of neurodegeneration (i.e., global and regional measures of brain volume) in early AD and non-demented aging. Fifty-five non-demented and 63 early AD participants underwent standard neurological and neuropsychological assessment, structural MRI scanning, and dual energy x-ray absorptiometry. In early AD, voxel-based morphometry analyses demonstrated that low BMD was associated with low volume in limbic grey matter (GM) including the hypothalamus, cingulate, and parahippocampal gyri and in the left superior temporal gyrus and left inferior parietal cortex. No relationship between BMD and regional GM volume was found in non-demented controls. The hypothesis-driven region of interest analysis further isolating the hypothalamus demonstrated a positive relationship between BMD and hypothalamic volume after controlling for age and gender in the early AD group but not in non-demented controls. These results demonstrate that lower BMD is associated with lower hypothalamic volume in early AD, suggesting that central mechanisms of bone remodeling may be disrupted by neurodegeneration.

Decisional impulsivity and the associative-limbic subthalamic nucleus in obsessive-compulsive disorder: stimulation and connectivity

PubMed Central

Voon, Valerie; Droux, Fabien; Morris, Laurel; Chabardes, Stephan; Bougerol, Thierry; David, Olivier; Krack, Paul; Polosan, Mircea

2017-01-01

Abstract Why do we make hasty decisions for short-term gain? Rapid decision-making with limited accumulation of evidence and delay discounting are forms of decisional impulsivity. The subthalamic nucleus is implicated in inhibitory function but its role in decisional impulsivity is less well-understood. Here we assess decisional impulsivity in subjects with obsessive compulsive disorder who have undergone deep brain stimulation of the limbic and associative subthalamic nucleus. We show that stimulation of the subthalamic nucleus is causally implicated in increasing decisional impulsivity with less accumulation of evidence during probabilistic uncertainty and in enhancing delay discounting. Subthalamic stimulation shifts evidence accumulation in subjects with obsessive-compulsive disorder towards a functional less cautious style closer to that of healthy controls emphasizing its adaptive nature. Thus, subjects with obsessive compulsive disorder on subthalamic stimulation may be less likely to check for evidence (e.g. checking that the stove is on) with no difference in subjective confidence (or doubt). In a separate study, we replicate in humans (154 healthy controls) using resting state functional connectivity, tracing studies conducted in non-human primates dissociating limbic, associative and motor frontal hyper-direct connectivity with anterior and posterior subregions of the subthalamic nucleus. We show lateralization of functional connectivity of bilateral ventral striatum to right anterior ventromedial subthalamic nucleus consistent with previous observations of lateralization of emotionally evoked activity to right ventral subthalamic nucleus. We use a multi-echo sequence with independent components analysis, which has been shown to have enhanced signal-to-noise ratio, thus optimizing visualization of small subcortical structures. These findings in healthy controls converge with the effective contacts in obsessive compulsive disorder patients localized within the anterior and ventral subthalamic nucleus. We further show that evidence accumulation is associated with anterior associative-limbic subthalamic nucleus and right dorsolateral prefrontal functional connectivity in healthy controls, a region implicated in decision-making under uncertainty. Together, our findings highlight specificity of the anterior associative-limbic subthalamic nucleus in decisional impulsivity. Given increasing interest in the potential for subthalamic stimulation in psychiatric disorders and the neuropsychiatric symptoms of Parkinson’s disease, these findings have clinical implications for behavioural symptoms and cognitive effects as a function of localization of subthalamic stimulation. PMID:28040671

Decisional impulsivity and the associative-limbic subthalamic nucleus in obsessive-compulsive disorder: stimulation and connectivity.

PubMed

Voon, Valerie; Droux, Fabien; Morris, Laurel; Chabardes, Stephan; Bougerol, Thierry; David, Olivier; Krack, Paul; Polosan, Mircea

2017-02-01

Why do we make hasty decisions for short-term gain? Rapid decision-making with limited accumulation of evidence and delay discounting are forms of decisional impulsivity. The subthalamic nucleus is implicated in inhibitory function but its role in decisional impulsivity is less well-understood. Here we assess decisional impulsivity in subjects with obsessive compulsive disorder who have undergone deep brain stimulation of the limbic and associative subthalamic nucleus. We show that stimulation of the subthalamic nucleus is causally implicated in increasing decisional impulsivity with less accumulation of evidence during probabilistic uncertainty and in enhancing delay discounting. Subthalamic stimulation shifts evidence accumulation in subjects with obsessive-compulsive disorder towards a functional less cautious style closer to that of healthy controls emphasizing its adaptive nature. Thus, subjects with obsessive compulsive disorder on subthalamic stimulation may be less likely to check for evidence (e.g. checking that the stove is on) with no difference in subjective confidence (or doubt). In a separate study, we replicate in humans (154 healthy controls) using resting state functional connectivity, tracing studies conducted in non-human primates dissociating limbic, associative and motor frontal hyper-direct connectivity with anterior and posterior subregions of the subthalamic nucleus. We show lateralization of functional connectivity of bilateral ventral striatum to right anterior ventromedial subthalamic nucleus consistent with previous observations of lateralization of emotionally evoked activity to right ventral subthalamic nucleus. We use a multi-echo sequence with independent components analysis, which has been shown to have enhanced signal-to-noise ratio, thus optimizing visualization of small subcortical structures. These findings in healthy controls converge with the effective contacts in obsessive compulsive disorder patients localized within the anterior and ventral subthalamic nucleus. We further show that evidence accumulation is associated with anterior associative-limbic subthalamic nucleus and right dorsolateral prefrontal functional connectivity in healthy controls, a region implicated in decision-making under uncertainty. Together, our findings highlight specificity of the anterior associative-limbic subthalamic nucleus in decisional impulsivity. Given increasing interest in the potential for subthalamic stimulation in psychiatric disorders and the neuropsychiatric symptoms of Parkinson's disease, these findings have clinical implications for behavioural symptoms and cognitive effects as a function of localization of subthalamic stimulation. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Impaired cortico-limbic functional connectivity in schizophrenia patients during emotion processing.

PubMed

Comte, Magali; Zendjidjian, Xavier Y; Coull, Jennifer T; Cancel, Aïda; Boutet, Claire; Schneider, Fabien C; Sage, Thierry; Lazerges, Pierre-Emmanuel; Jaafari, Nematollah; Ibrahim, El Chérif; Azorin, Jean-Michel; Blin, Olivier; Fakra, Eric

2017-10-23

Functional dysconnection is increasingly recognized as a core pathological feature in schizophrenia. Aberrant interactions between regions of the cortico-limbic circuit may underpin the abnormal emotional processing associated with this illness. We used a functional magnetic resonance imaging (fMRI) paradigm designed to dissociate the various components of the cortico-limbic circuit (i.e. a ventral automatic circuit that is intertwined with a dorsal cognitive circuit), in order to explore bottom-up appraisal as well as top-down control during emotion processing. In schizophrenia patients compared to healthy controls, bottom-up processes were associated with reduced interaction between the amygdala and both the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). Contrariwise, top-down control processes led to stronger connectivity between the ventral affective and the dorsal cognitive circuits, i.e. heightened interactions between the ventral ACC and the DLPFC as well as between dorsal and ventral ACC. These findings offer a comprehensive view of the cortico-limbic dysfunction in schizophrenia. They confirm previous results of impaired propagation of information between the amygdala and the prefrontal cortex and suggest a defective functional segregation in the dorsal cognitive part of the cortico-limbic circuit. © The Author (2017). Published by Oxford University Press.

Impaired cortico-limbic functional connectivity in schizophrenia patients during emotion processing

PubMed Central

Comte, Magali; Zendjidjian, Xavier Y; Coull, Jennifer T; Cancel, Aïda; Boutet, Claire; Schneider, Fabien C; Sage, Thierry; Lazerges, Pierre-Emmanuel; Jaafari, Nematollah; Ibrahim, El Chérif; Azorin, Jean-Michel; Blin, Olivier; Fakra, Eric

2018-01-01

Abstract Functional dysconnection is increasingly recognized as a core pathological feature in schizophrenia. Aberrant interactions between regions of the cortico-limbic circuit may underpin the abnormal emotional processing associated with this illness. We used a functional magnetic resonance imaging paradigm designed to dissociate the various components of the cortico-limbic circuit (i.e. a ventral automatic circuit that is intertwined with a dorsal cognitive circuit), to explore bottom-up appraisal as well as top-down control during emotion processing. In schizophrenia patients compared with healthy controls, bottom-up processes were associated with reduced interaction between the amygdala and both the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex. Contrariwise, top-down control processes led to stronger connectivity between the ventral affective and the dorsal cognitive circuits, i.e. heightened interactions between the ventral ACC and the dorsolateral prefrontal cortex as well as between dorsal and ventral ACC. These findings offer a comprehensive view of the cortico-limbic dysfunction in schizophrenia. They confirm previous results of impaired propagation of information between the amygdala and the prefrontal cortex and suggest a defective functional segregation in the dorsal cognitive part of the cortico-limbic circuit. PMID:29069508

Neuroimaging and cognitive changes during déjà vu.

PubMed

Kovacs, Norbert; Auer, Tibor; Balas, Istvan; Karadi, Kazmer; Zambo, Katalin; Schwarcz, Attila; Klivenyi, Peter; Jokeit, Hennric; Horvath, Krisztina; Nagy, Ferenc; Janszky, Jozsef

2009-01-01

The cause or the physiological role of déjà vu (DV) in healthy people is unknown. The pathophysiology of DV-type epileptic aura is also unresolved. Here we describe a 22-year-old woman treated with deep brain stimulation (DBS) of the left internal globus pallidus for hemidystonia. At certain stimulation settings, DBS elicited reproducible episodes of DV. Neuropsychological tests and single-photon-emission computed tomography (SPECT) were performed during DBS-evoked DV and during normal DBS stimulation without DV. SPECT during DBS-evoked DV revealed hyperperfusion of the right (contralateral to the electrode) hippocampus and other limbic structures. Neuropsychological examinations performed during several evoked DV episodes revealed disturbances in nonverbal memory. Our results confirm the role of mesiotemporal structures in the pathogenesis of DV. We hypothesize that individual neuroanatomy and disturbances in gamma oscillations or in the dopaminergic system played a role in DBS-elicited DV in our patient.

Medial Demons Registration Localizes The Degree of Genetic Influence Over Subcortical Shape Variability: An N= 1480 Meta-Analysis

PubMed Central

Gutman, Boris A.; Jahanshad, Neda; Ching, Christopher R.K.; Wang, Yalin; Kochunov, Peter V.; Nichols, Thomas E.; Thompson, Paul M.

2015-01-01

We present a multi-cohort shape heritability study, extending the fast spherical demons registration to subcortical shapes via medial modeling. A multi-channel demons registration based on vector spherical harmonics is applied to medial and curvature features, while controlling for metric distortion. We registered and compared seven subcortical structures of 1480 twins and siblings from the Queensland Twin Imaging Study and Human Connectome Project: Thalamus, Caudate, Putamen, Pallidum, Hippocampus, Amygdala, and Nucleus Accumbens. Radial distance and tensor-based morphometry (TBM) features were found to be highly heritable throughout the entire basal ganglia and limbic system. Surface maps reveal subtle variation in heritability across functionally distinct parts of each structure. Medial Demons reveals more significantly heritable regions than two previously described surface registration methods. This approach may help to prioritize features and measures for genome-wide association studies. PMID:26413211

Medial Demons Registration Localizes The Degree of Genetic Influence Over Subcortical Shape Variability: An N= 1480 Meta-Analysis.

PubMed

Gutman, Boris A; Jahanshad, Neda; Ching, Christopher R K; Wang, Yalin; Kochunov, Peter V; Nichols, Thomas E; Thompson, Paul M

2015-04-01

We present a multi-cohort shape heritability study, extending the fast spherical demons registration to subcortical shapes via medial modeling. A multi-channel demons registration based on vector spherical harmonics is applied to medial and curvature features, while controlling for metric distortion. We registered and compared seven subcortical structures of 1480 twins and siblings from the Queensland Twin Imaging Study and Human Connectome Project: Thalamus, Caudate, Putamen, Pallidum, Hippocampus, Amygdala, and Nucleus Accumbens . Radial distance and tensor-based morphometry (TBM) features were found to be highly heritable throughout the entire basal ganglia and limbic system. Surface maps reveal subtle variation in heritability across functionally distinct parts of each structure. Medial Demons reveals more significantly heritable regions than two previously described surface registration methods. This approach may help to prioritize features and measures for genome-wide association studies.

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

PubMed

Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

2017-02-01

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contribution of early environmental stress to alcoholism vulnerability.

PubMed

Campbell, Joannalee C; Szumlinski, Karen K; Kippin, Tod E

2009-11-01

The most problematic aspects of alcohol abuse disorder are excessive alcohol consumption and the inability to refrain from alcohol consumption during attempted abstinence. The root causes that predispose certain individuals to these problems are poorly understood but are believed to be produced by a combination of genetic and environmental factors. Early environmental trauma alters neurodevelopmental trajectories that can predispose an individual to a number of neuropsychiatric disorders, including substance abuse. Prenatal stress (PNS) is a well-established protocol that produces perturbations in nervous system development, resulting in behavioral alterations that include hyperresponsiveness to stress, novelty, and psychomotor stimulant drugs (e.g., cocaine, amphetamine). Moreover, PNS animals exhibit enduring alterations in basal and cocaine-induced changes in dopamine and glutamate transmission within limbic structures, which exhibit pathology in drug addiction and alcoholism, suggesting that these alterations may contribute to an increased propensity to self-administer large amounts of drugs of abuse or to relapse after periods of drug withdrawal. Given that cocaine and alcohol have actions on common limbic neural substrates (albeit by different mechanisms), we hypothesized that PNS would elevate the motivation for, and consumption of, alcohol. Accordingly, we have found that male C57BL/6J mice subject to PNS exhibit higher operant responding and consume more alcohol during alcohol reinforcement as adults. Alterations in glutamate and dopamine neurotransmission within the forebrain structures appear to contribute to the PNS-induced predisposition to high alcohol intake and are induced by excessive alcohol intake. Accordingly, we are exploring the interactions between neurochemical changes produced by PNS and changes induced by consumption of alcohol in adulthood to model the biological bases of high vulnerability to alcohol abuse.

Contribution of early environmental stress to alcoholism vulnerability

PubMed Central

Campbell, Joannalee C.; Szumlinski, Karen K.; Kippin, Tod E.

2011-01-01

The most problematic aspects of alcohol abuse disorder are excessive alcohol consumption and the inability to refrain from alcohol consumption during attempted abstinence. The root causes that predispose certain individuals to these problems are poorly understood but are believed to be produced by a combination of genetic and environmental factors. Early environmental trauma alters neurodevelopmental trajectories that can predispose an individual to a number of neuropsychiatric disorders, including substance abuse. Prenatal stress (PNS) is a well-established protocol that produces perturbations in nervous system development, resulting in behavioral alterations that include hyperresponsiveness to stress, novelty, and psychomotor stimulant drugs (e.g., cocaine, amphetamine). Moreover, PNS animals exhibit enduring alterations in basal and cocaine-induced changes in dopamine and glutamate transmission within limbic structures, which exhibit pathology in drug addiction and alcoholism, suggesting that these alterations may contribute to an increased propensity to self-administer large amounts of drugs of abuse or to relapse after periods of drug withdrawal. Given that cocaine and alcohol have actions on common limbic neural substrates (albeit by different mechanisms), we hypothesized that PNS would elevate the motivation for, and consumption of, alcohol. Accordingly, we have found that male C57BL/6J mice subject to PNS exhibit higher operant responding and consume more alcohol during alcohol reinforcement as adults. Alterations in glutamate and dopamine neurotransmission within the forebrain structures appear to contribute to the PNS-induced predisposition to high alcohol intake and are induced by excessive alcohol intake. Accordingly, we are exploring the interactions between neurochemical changes produced by PNS and changes induced by consumption of alcohol in adulthood to model the biological bases of high vulnerability to alcohol abuse. PMID:19913199

Functional Connectivity Bias in the Prefrontal Cortex of Psychopaths.

PubMed

Contreras-Rodríguez, Oren; Pujol, Jesus; Batalla, Iolanda; Harrison, Ben J; Soriano-Mas, Carles; Deus, Joan; López-Solà, Marina; Macià, Dídac; Pera, Vanessa; Hernández-Ribas, Rosa; Pifarré, Josep; Menchón, José M; Cardoner, Narcís

2015-11-01

Psychopathy is characterized by a distinctive interpersonal style that combines callous-unemotional traits with inflexible and antisocial behavior. Traditional emotion-based perspectives link emotional impairment mostly to alterations in amygdala-ventromedial frontal circuits. However, these models alone cannot explain why individuals with psychopathy can regularly benefit from emotional information when placed on their focus of attention and why they are more resistant to interference from nonaffective contextual cues. The present study aimed to identify abnormal or distinctive functional links between and within emotional and cognitive brain systems in the psychopathic brain to characterize further the neural bases of psychopathy. High-resolution anatomic magnetic resonance imaging with a functional sequence acquired in the resting state was used to assess 22 subjects with psychopathy and 22 control subjects. Anatomic and functional connectivity alterations were investigated first using a whole-brain analysis. Brain regions showing overlapping anatomic and functional changes were examined further using seed-based functional connectivity mapping. Subjects with psychopathy showed gray matter reduction involving prefrontal cortex, paralimbic, and limbic structures. Anatomic changes overlapped with areas showing increased degree of functional connectivity at the medial-dorsal frontal cortex. Subsequent functional seed-based connectivity mapping revealed a pattern of reduced functional connectivity of prefrontal areas with limbic-paralimbic structures and enhanced connectivity within the dorsal frontal lobe in subjects with psychopathy. Our results suggest that a weakened link between emotional and cognitive domains in the psychopathic brain may combine with enhanced functional connections within frontal executive areas. The identified functional alterations are discussed in the context of potential contributors to the inflexible behavior displayed by individuals with psychopathy. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Interprofessional learning in primary care: an exploration of the service user experience leads to a new model for co-learning.

PubMed

Worswick, Louise; Little, Christine; Ryan, Kath; Carr, Eloise

2015-01-01

Research about service user involvement in research and education focuses on the purpose, the methods, the barriers and the impact of their involvement. Few studies report on the experience of the service users who get involved. This paper reports an exploration of the experience of service users who participated in an interprofessional educational initiative in primary care - the Learning to Improve the Management of Back Pain in the Community (LIMBIC) project. Service users attended workshops with practice teams and assisted them in developing small scale quality improvement projects to improve their provision of care for people with back pain. To explore the experience of service users involved in the LIMBIC project. Using the philosophical and methodological approaches of pragmatism this study analysed data from the wider LIMBIC project and collected primary data through semi structured interviews with service users. Secondary data were reanalysed and integrated with primary data to address the research question. The study was undertaken in the primary health care setting. Patients participated as service users in workshops and quality improvement projects with members from their practice teams. Interviews with service users were transcribed and analysed thematically. Document and thematic analyses of secondary data from the LIMBIC project included focus group transcripts, patient stories, film, emails, meeting notes, a wiki and educational material such as presentations. Themes identified through the analyses illustrated the importance, to the service users, of the sense of community, of clear communication, and of influencing change through involvement. A model for co-learning with service users resulted from the analyses. The experience of service users can be optimised by planning, preparation and support so that their wealth of expertise can be recognised and utilised. A model for co-learning was developed and is presented in this paper. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inactivation of the Anterior Cingulate Cortex Impairs Extinction of Rabbit Jaw Movement Conditioning and Prevents Extinction-Related Inhibition of Hippocampal Activity

ERIC Educational Resources Information Center

Griffin, Amy L.; Berry, Stephen D.

2004-01-01

Although past research has highlighted the involvement of limbic structures such as the anterior cingulate cortex (ACC) and hippocampus in learning, few have addressed the nature of their interaction. The current study of rabbit jaw movement conditioning used a combination of reversible lesions and electrophysiology to examine the involvement of…

Molecular imaging of serotonin degeneration in mild cognitive impairment.

PubMed

Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

2017-09-01

Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic areas typically affected by Alzheimer's disease pathology, as well as in sensory and motor areas, striatum and thalamus that are relatively spared in Alzheimer's disease. The reduction of the serotonin transporter in mild cognitive impairment was greater than grey matter atrophy or reductions in regional cerebral blood flow compared to controls. Lower cortical serotonin transporters were associated with worse performance on tests of auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. The serotonin system may represent an important target for prevention and treatment of MCI, particularly the post-synaptic receptors (5-HT4 and 5-HT6), which may not be as severely affected as presynaptic aspects of the serotonin system, as indicated by the observation of lower serotonin transporters in MCI relative to healthy controls. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of adrenal cortex hormones on limbic structures: some experimental and clinical correlations related to depression.

PubMed Central

Dubrovsky, B

1993-01-01

Cushing's disorder and depression present overlapping although not identical psychological symptomatology. In turn, a subset of patients with affective disorders present with hypercortisolemia and disturbances, specifically disinhibition, of the hypothalamic hypophysio adrenal axis (HHAA). Memory disturbances, in particular, biasing toward negative contents, overlapping sleep abnormalities (marked reduction of stages 3 and 4) increased fatigue and loss of energy, attentional deficits and irritability, are just part of the common symptomatology presented by patients with both Cushing's disorder and depression. All of these behavioral manifestations are known to be affected by adrenal steroid hormones. There is consensus that hippocampal structures are a main target for adrenal steroid hormones; hence, these neural regions are some of the most likely mediators of the effects of corticoadrenal steroids on behavior. This paper proposes that an imbalance of adrenal steroids and their metabolites may play a fundamental role in the psychophysiopathology of Cushing's and depressive disorders. The imbalance of these hormones, especially at limbic sites, could distort mood and memory content affecting cognition based on recollection and present experiences. Reestablishing an adrenal balance could therefore be considered as a therapeutic aid in a subset of depressive disorders. PMID:8461280

Effect of Explicit Evaluation on Neural Connectivity Related to Listening to Unfamiliar Music

PubMed Central

Liu, Chao; Brattico, Elvira; Abu-jamous, Basel; Pereira, Carlos S.; Jacobsen, Thomas; Nandi, Asoke K.

2017-01-01

People can experience different emotions when listening to music. A growing number of studies have investigated the brain structures and neural connectivities associated with perceived emotions. However, very little is known about the effect of an explicit act of judgment on the neural processing of emotionally-valenced music. In this study, we adopted the novel consensus clustering paradigm, called binarisation of consensus partition matrices (Bi-CoPaM), to study whether and how the conscious aesthetic evaluation of the music would modulate brain connectivity networks related to emotion and reward processing. Participants listened to music under three conditions – one involving a non-evaluative judgment, one involving an explicit evaluative aesthetic judgment, and one involving no judgment at all (passive listening only). During non-evaluative attentive listening we obtained auditory-limbic connectivity whereas when participants were asked to decide explicitly whether they liked or disliked the music excerpt, only two clusters of intercommunicating brain regions were found: one including areas related to auditory processing and action observation, and the other comprising higher-order structures involved with visual processing. Results indicate that explicit evaluative judgment has an impact on the neural auditory-limbic connectivity during affective processing of music. PMID:29311874

Kainic acid-induced albumin leak across the blood-brain barrier facilitates epileptiform hyperexcitability in limbic regions.

PubMed

Noé, Francesco M; Bellistri, Elisa; Colciaghi, Francesca; Cipelletti, Barbara; Battaglia, Giorgio; de Curtis, Marco; Librizzi, Laura

2016-06-01

Systemic administration of kainic acid (KA) is a widely used procedure utilized to develop a model of temporal lobe epilepsy (TLE). Despite its ability to induce status epilepticus (SE) in vivo, KA applied to in vitro preparations induces only interictal-like activity and/or isolated ictal discharges. The possibility that extravasation of the serum protein albumin from the vascular compartment enhances KA-induced brain excitability is investigated here. Epileptiform activity was induced by arterial perfusion of 6 μm KA in the in vitro isolated guinea pig brain preparation. Simultaneous field potential recordings were carried out bilaterally from limbic (CA1, dentate gyrus [DG], and entorhinal cortex) and extralimbic regions (piriform cortex and neocortex). Blood-brain barrier (BBB) breakdown associated with KA-induced epileptiform activity was assessed by parenchymal leakage of intravascular fluorescein-isothiocyanate albumin. Seizure-induced brain inflammation was evaluated by western blot analysis of interleukin (IL)-1β expression in brain tissue. KA infusion caused synchronized activity at 15-30 Hz in limbic (but not extralimbic) cortical areas, associated with a brief, single seizure-like event. A second bolus of KA, 60 min after the induction of the first ictal event, did not further enhance excitability. Perfusion of serum albumin between the two administrations of KA enhanced epileptiform discharges and allowed a recurrent ictal event during the second KA infusion. Our data show that arterial KA administration selectively alters the synchronization of limbic networks. However, KA is not sufficient to generate recurrent seizures unless serum albumin is co-perfused during KA administration. These findings suggest a role of serum albumin in facilitating acute seizure generation. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Portraying emotions at their unfolding: a multilayered approach for probing dynamics of neural networks.

PubMed

Raz, Gal; Winetraub, Yonatan; Jacob, Yael; Kinreich, Sivan; Maron-Katz, Adi; Shaham, Galit; Podlipsky, Ilana; Gilam, Gadi; Soreq, Eyal; Hendler, Talma

2012-04-02

Dynamic functional integration of distinct neural systems plays a pivotal role in emotional experience. We introduce a novel approach for studying emotion-related changes in the interactions within and between networks using fMRI. It is based on continuous computation of a network cohesion index (NCI), which is sensitive to both strength and variability of signal correlations between pre-defined regions. The regions encompass three clusters (namely limbic, medial prefrontal cortex (mPFC) and cognitive), each previously was shown to be involved in emotional processing. Two sadness-inducing film excerpts were viewed passively, and comparisons between viewer's rated sadness, parasympathetic, and inter-NCI and intra-NCI were obtained. Limbic intra-NCI was associated with reported sadness in both movies. However, the correlation between the parasympathetic-index, the rated sadness and the limbic-NCI occurred in only one movie, possibly related to a "deactivated" pattern of sadness. In this film, rated sadness intensity also correlated with the mPFC intra-NCI, possibly reflecting temporal correspondence between sadness and sympathy. Further, only for this movie, we found an association between sadness rating and the mPFC-limbic inter-NCI time courses. To the contrary, in the other film in which sadness was reported to commingle with horror and anger, dramatic events coincided with disintegration of these networks. Together, this may point to a difference between the cinematic experiences with regard to inter-network dynamics related to emotional regulation. These findings demonstrate the advantage of a multi-layered dynamic analysis for elucidating the uniqueness of emotional experiences with regard to an unguided processing of continuous and complex stimulation. Copyright © 2012 Elsevier Inc. All rights reserved.

CB1 Cannabinoid Receptor Expression in the Striatum: Association with Corticostriatal Circuits and Developmental Regulation

PubMed Central

Van Waes, Vincent; Beverley, Joel A.; Siman, Homayoun; Tseng, Kuei Y.; Steiner, Heinz

2012-01-01

Corticostriatal circuits mediate various aspects of goal-directed behavior and are critically important for basal ganglia-related disorders. Activity in these circuits is regulated by the endocannabinoid system via stimulation of CB1 cannabinoid receptors. CB1 receptors are highly expressed in projection neurons and select interneurons of the striatum, but expression levels vary considerably between different striatal regions (functional domains). We investigated CB1 receptor expression within specific corticostriatal circuits by mapping CB1 mRNA levels in striatal sectors defined by their cortical inputs in rats. We also assessed changes in CB1 expression in the striatum during development. Our results show that CB1 expression is highest in juveniles (P25) and then progressively decreases toward adolescent (P40) and adult (P70) levels. At every age, CB1 receptors are predominantly expressed in sensorimotor striatal sectors, with considerably lower expression in associative and limbic sectors. Moreover, for most corticostriatal circuits there is an inverse relationship between cortical and striatal expression levels. Thus, striatal sectors with high CB1 expression (sensorimotor sectors) tend to receive inputs from cortical areas with low expression, while striatal sectors with low expression (associative/limbic sectors) receive inputs from cortical regions with higher expression (medial prefrontal cortex). In so far as CB1 mRNA levels reflect receptor function, our findings suggest differential CB1 signaling between different developmental stages and between sensorimotor and associative/limbic circuits. The regional distribution of CB1 receptor expression in the striatum further suggests that, in sensorimotor sectors, CB1 receptors mostly regulate GABA inputs from local axon collaterals of projection neurons, whereas in associative/limbic sectors, CB1 regulation of GABA inputs from interneurons and glutamate inputs may be more important. PMID:22416230

Topologically convergent and divergent functional connectivity patterns in unmedicated unipolar depression and bipolar disorder.

PubMed

Wang, Y; Wang, J; Jia, Y; Zhong, S; Zhong, M; Sun, Y; Niu, M; Zhao, L; Zhao, L; Pan, J; Huang, L; Huang, R

2017-07-04

Bipolar disorder (BD), particularly BD II, is frequently misdiagnosed as unipolar depression (UD), leading to inappropriate treatment and poor clinical outcomes. Although depressive symptoms may be expressed similarly in UD and BD, the similarities and differences in the architecture of brain functional networks between the two disorders are still unknown. In this study, we hypothesized that UD and BD II patients would show convergent and divergent patterns of disrupted topological organization of the functional connectome, especially in the default mode network (DMN) and the limbic network. Brain resting-state functional magnetic resonance imaging (fMRI) data were acquired from 32 UD-unmedicated patients, 31 unmedicated BD II patients (current episode depressed) and 43 healthy subjects. Using graph theory, we systematically studied the topological organization of their whole-brain functional networks at the following three levels: whole brain, modularity and node. First, both the UD and BD II patients showed increased characteristic path length and decreased global efficiency compared with the controls. Second, both the UD and BD II patients showed disrupted intramodular connectivity within the DMN and limbic system network. Third, decreased nodal characteristics (nodal strength and nodal efficiency) were found predominantly in brain regions in the DMN, limbic network and cerebellum of both the UD and BD II patients, whereas differences between the UD and BD II patients in the nodal characteristics were also observed in the precuneus and temporal pole. Convergent deficits in the topological organization of the whole brain, DMN and limbic networks may reflect overlapping pathophysiological processes in unipolar and bipolar depression. Our discovery of divergent regional connectivity that supports emotion processing could help to identify biomarkers that will aid in differentiating these disorders.

Topologically convergent and divergent functional connectivity patterns in unmedicated unipolar depression and bipolar disorder

PubMed Central

Wang, Y; Wang, J; Jia, Y; Zhong, S; Zhong, M; Sun, Y; Niu, M; Zhao, L; Zhao, L; Pan, J; Huang, L; Huang, R

2017-01-01

Bipolar disorder (BD), particularly BD II, is frequently misdiagnosed as unipolar depression (UD), leading to inappropriate treatment and poor clinical outcomes. Although depressive symptoms may be expressed similarly in UD and BD, the similarities and differences in the architecture of brain functional networks between the two disorders are still unknown. In this study, we hypothesized that UD and BD II patients would show convergent and divergent patterns of disrupted topological organization of the functional connectome, especially in the default mode network (DMN) and the limbic network. Brain resting-state functional magnetic resonance imaging (fMRI) data were acquired from 32 UD-unmedicated patients, 31 unmedicated BD II patients (current episode depressed) and 43 healthy subjects. Using graph theory, we systematically studied the topological organization of their whole-brain functional networks at the following three levels: whole brain, modularity and node. First, both the UD and BD II patients showed increased characteristic path length and decreased global efficiency compared with the controls. Second, both the UD and BD II patients showed disrupted intramodular connectivity within the DMN and limbic system network. Third, decreased nodal characteristics (nodal strength and nodal efficiency) were found predominantly in brain regions in the DMN, limbic network and cerebellum of both the UD and BD II patients, whereas differences between the UD and BD II patients in the nodal characteristics were also observed in the precuneus and temporal pole. Convergent deficits in the topological organization of the whole brain, DMN and limbic networks may reflect overlapping pathophysiological processes in unipolar and bipolar depression. Our discovery of divergent regional connectivity that supports emotion processing could help to identify biomarkers that will aid in differentiating these disorders. PMID:28675389

Cognition, emotion, and attention.

PubMed

Müller-Oehring, Eva M; Schulte, Tilman

2014-01-01

Deficits of attention, emotion, and cognition occur in individuals with alcohol abuse and addiction. This review elucidates the concepts of attention, emotion, and cognition and references research on the underlying neural networks and their compromise in alcohol use disorder. Neuroimaging research on adolescents with family history of alcoholism contributes to the understanding of pre-existing brain structural conditions and characterization of cognition and attention processes in high-risk individuals. Attention and cognition interact with other brain functions, including perceptual selection, salience, emotion, reward, and memory, through interconnected neural networks. Recent research reports compromised microstructural and functional network connectivity in alcoholism, which can have an effect on the dynamic tuning between brain systems, e.g., the frontally based executive control system, the limbic emotion system, and the midbrain-striatal reward system, thereby impeding cognitive flexibility and behavioral adaptation to changing environments. Finally, we introduce concepts of functional compensation, the capacity to generate attentional resources for performance enhancement, and brain structure recovery with abstinence. An understanding of the neural mechanisms of attention, emotion, and cognition will likely provide the basis for better treatment strategies for developing skills that enhance alcoholism therapy adherence and quality of life, and reduce the propensity for relapse. © 2014 Elsevier B.V. All rights reserved.

[Tinnitus and psychiatric comorbidities].

PubMed

Goebel, G

2015-04-01

Tinnitus is an auditory phantom phenomenon characterized by the sensation of sounds without objectively identifiable sound sources. To date, its causes are not well understood. The perceived severity of tinnitus correlates more closely to psychological and general health factors than to audiometric parameters. Together with limbic structures in the ventral striatum, the prefrontal cortex forms an internal "noise cancelling system", which normally helps to block out unpleasant sounds, including the tinnitus signal. If this pathway is compromised, chronic tinnitus results. Patients with chronic tinnitus show increased functional connectivity in corticolimbic pathways. Psychiatric comorbidities are common in patients who seek help for tinnitus or hyperacusis. Clinicians need valid screening tools in order to identify patients with psychiatric disorders and to tailor treatment in a multidisciplinary setting.

Neural correlates of corporate camaraderie and teamwork.

PubMed

Levine, Catherine

2007-11-01

Corporate citizenship creates an ethical and professional accountability among the employee, the organization, and the outside market. Teamwork is an essential part of this corporate accountability because it increases communication and confidence within the organization and promotes camaraderie and goal completion. Cognitive neuroscience research has been able to localize socialization to various areas of the limbic system, which includes, among other structures, the hypothalamus and amygdala, and is associated with the prefrontal cortex. These neurocortical areas can be monitored while set tasks are performed experimentally or observed naturally. Within the framework of cognitive neuroscience, one can evaluate the neural architecture involved in various states of organizational behavior. One can then use this framework as an overlay in the corporate environment to track project completion and profitability.

Exercise, Obesity and CNS Control of Metabolic Homeostasis: A Review

PubMed Central

Smith, John K.

2018-01-01

This review details the manner in which the central nervous system regulates metabolic homeostasis in normal weight and obese rodents and humans. It includes a review of the homeostatic contributions of neurons located in the hypothalamus, the midbrain and limbic structures, the pons and the medullary area postrema, nucleus tractus solitarius, and vagus nucleus, and details how these brain regions respond to circulating levels of orexigenic hormones, such as ghrelin, and anorexigenic hormones, such as glucagon-like peptide 1 and leptin. It provides an insight as to how high intensity exercise may improve homeostatic control in overweight and obese subjects. Finally, it provides suggestions as to how further progress can be made in controlling the current pandemic of obesity and diabetes. PMID:29867590

The Brain: Its Relationship to Learning, Emotional States, and Behavior

ERIC Educational Resources Information Center

Armstrong, Terry

1977-01-01

Outlines findings of contemporary neuro-scientists studying the biological basis of human learning and behavior. Areas of research discussed are: (1) the center of human emotion--the limbic system; (2) brain rhythms; and (3) the molecular basis of learning. (CS)

Anatomy of the Limbic White Matter Tracts as Revealed by Fiber Dissection and Tractography.

PubMed

Pascalau, Raluca; Popa Stănilă, Roxana; Sfrângeu, Silviu; Szabo, Bianca

2018-05-01

The limbic tracts are involved in crucial cerebral functions such as memory, emotion, and behavior. The complex architecture of the limbic circuit makes it harder to approach compared with other white matter networks. Our study aims to describe the 3-dimensional anatomy of the limbic white matter by the use of 2 complementary study methods, namely ex vivo fiber dissection and in vivo magnetic resonance imaging-based tractography. Three fiber dissection protocols were performed using blunt wooden instruments and a surgical microscope on formalin-fixed brains prepared according to the Klingler method. Diffusion tensor imaging acquisitions were done with a 3-Tesla magnetic resonance scanner on patients with head and neck pathology that did not involve the brain. Fiber tracking was performed with manually selected regions of interest. Cingulum, fornix, the anterior thalamic peduncle, the accumbofrontal bundle, medial forebrain bundle, the uncinate fasciculus, the mammillothalamic tract, ansa peduncularis, and stria terminalis were dissected and fiber tracked. For each tract, location, configuration, segmentation, dimensions, dissection and tractography particularities, anatomical relations, and terminations are described. The limbic white matter tracts were systematized as 2 concentric rings around the thalamus. The inner ring is formed by fornix, mammillothalamic tract, ansa peduncularis, stria terminalis, accumbofrontal fasciculus, and medial forebrain bundle and anterior thalamic peduncle, and the outer ring is formed by the cingulum and uncinate fasciculus. This paper proposes a fiber-tracking protocol for the limbic tracts inspired and validated by fiber dissection findings that can be used routinely in the clinical practice. Copyright © 2018 Elsevier Inc. All rights reserved.

Previous exposure to (+/-) 3,4-methylenedioxymethamphetamine produces long-lasting alteration in limbic brain excitability measured by electroencephalogram spectrum analysis, brain metabolism and seizure susceptibility.

PubMed

Giorgi, F S; Pizzanelli, C; Ferrucci, M; Lazzeri, G; Faetti, M; Giusiani, M; Pontarelli, F; Busceti, C L; Murri, L; Fornai, F

2005-01-01

Seizures represent the most common neurological emergency in ecstasy abusers; however, no study addressed whether (+/-) 3,4-methylenedioxymethamphetamine ("ecstasy") per se might produce long-lasting alterations in brain excitability related to a pro-convulsant effect. C57 Black mice were treated with three regimens of (+/-) 3,4-methylenedioxymethamphetamine (5mg/kg x 2 for 1, 2 or three consecutive days). Following the last dose of (+/-) 3,4-methylenedioxymethamphetamine, during a time interval of 8 weeks, the following procedures were carried out: 1) cortical electroencephalographic recordings, including power-spectrum analysis; 2) administration of sub-threshold doses of kainate; 3) measurement of regional [(14)C]2-deoxyglucose uptake; 4) monoamine assay. We demonstrate that all mice pre-treated with (+/-) 3,4-methylenedioxymethamphetamine showed long-lasting encephalographic changes with frequencies peaking at 3-4.5 Hz at the power-spectrum analysis. This is concomitant with latent brain hyperexcitability within selected limbic brain regions, as shown by seizure facilitation and long-lasting latent metabolic hyperactivity which can be unraveled by phasic glutamate stimulation. This study sheds new light into the brain targets of (+/-) 3,4-methylenedioxymethamphetamine and discloses the occurrence of (+/-) 3,4-methylenedioxymethamphetamine-induced latent hyperexcitability within limbic areas, while it might provide a model to study in controlled experimental conditions limbic seizures and status epilepticus in C57 Black mice. Persistent changes produced by (+/-) 3,4-methylenedioxymethamphetamine in limbic brain excitability might be responsible for seizures and limbic-related disorders in chronic (+/-) 3,4-methylenedioxymethamphetamine abusers.

Application of fractal dimension method of functional MRI time-series to limbic dysregulation in anxiety study.

PubMed

Olejarczyk, Elzbieta

2007-01-01

Functional magnetic resonance imaging (fMRI) allows to investigate the amplitude of activation in neural networks of brain. In this work we present the results of fMRI time-series analysis performed to identify the process of dysregulation of dynamic interaction between different limbic system regions in healthy adults in state of increased anxiety. The results obtain for 65 healthy adults using nonlinear dynamics methods like fractal dimension confirm the key roles of the bilateral amygdala, bilateral hippocampus, BA9 (dorsolateral prefrontal cortex), and BA45 (ventromedial prefrontal cortex) in modulating emotional response in healthy adults. For different regions of interest (ROIs) significant correlations were found not only for the neutral respective rest but also for fear and angry contrasts.

Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: Preliminary results

PubMed Central

Charboneau, Evonne J.; Dietrich, Mary S.; Park, Sohee; Cao, Aize; Watkins, Tristan J; Blackford, Jennifer U; Benningfield, Margaret M.; Martin, Peter R.; Buchowski, Maciej S.; Cowan, Ronald L.

2013-01-01

Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood. This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals. Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI (fMRI) scan. The Marijuana Craving Questionnaire was administered immediately before and after each of three cannabis cue-exposure fMRI runs. FMRI blood-oxygenation-level-dependent (BOLD) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving. Craving scores increased significantly following exposure to visual cannabis cues. Visual cues activated multiple brain regions, including inferior orbital frontal cortex, posterior cingulate gyrus, parahippocampal gyrus, hippocampus, amygdala, superior temporal pole, and occipital cortex. Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only, in the limbic system (including amygdala and hippocampus) and paralimbic system (superior temporal pole), and visual regions (occipital cortex). Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic, paralimbic, and visual systems during the first fMRI run, but not subsequent fMRI runs. These results suggest that these regions may mediate visually cued aspects of drug craving. This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence. PMID:24035535

Curcuma treatment prevents cognitive deficit and alteration of neuronal morphology in the limbic system of aging rats.

PubMed

Vidal, Blanca; Vázquez-Roque, Rubén A; Gnecco, Dino; Enríquez, Raúl G; Floran, Benjamin; Díaz, Alfonso; Flores, Gonzalo

2017-03-01

Curcuma is a natural compound that has shown neuroprotective properties, and has been reported to prevent aging and improve memory. While the mechanism(s) underlying these effects are unclear, they may be related to increases in neural plasticity. Morphological changes have been reported in neuronal dendrites in the limbic system in animals and elderly humans with cognitive impairment. In this regard, there is a need to use alternative therapies that delay the onset of morphologies and behavioral characteristics of aging. Therefore, the objective of this study was to evaluate the effect of curcuma on cognitive processes and dendritic morphology of neurons in the prefrontal cortex (PFC), the CA1 and CA3 regions of the dorsal hippocampus, the dentate gyrus, and the basolateral amygdala (BLA) of aged rats. 18-month-old rats were administered curcuma (100 mg/kg) daily for 60 days. After treatment, recognition memory was assessed using the novel object recognition test. Curcuma-treated rats showed a significant increase in the exploration quotient. Dendritic morphology was assessed by Golgi-Cox staining and followed by Sholl analysis. Curcuma-treated rats showed a significant increase in dendritic spine density and dendritic length in pyramidal neurons of the PFC, the CA1 and CA3, and the BLA. The preservation of dendritic morphology was positively correlated with cognitive improvements. Our results suggest that curcuma induces modification of dendritic morphology in the aforementioned regions. These changes may explain how curcuma slows the aging process that has already begun in these animals, preventing deterioration in neuronal morphology of the limbic system and recognition memory. © 2016 Wiley Periodicals, Inc.

The International Society for Developmental Psychobiology Annual Meeting Symposium: Impact of Early Life Experiences on Brain and Behavioral Development

PubMed Central

Sullivan, Regina; Wilson, Donald A.; Feldon, Joram; Yee, Benjamin K.; Meyer, Urs; Richter-Levin, Gal; Avi, Avital; Michael, Tsoory; Gruss, Michael; Bock, Jörg; Helmeke, Carina; Braun, Katharina

2007-01-01

Decades of research in the area of developmental psychobiology have shown that early life experience alters behavioral and brain development, which canalizes development to suit different environments. Recent methodological advances have begun to identify the mechanisms by which early life experiences cause these diverse adult outcomes. Here we present four different research programs that demonstrate the intricacies of early environmental influences on behavioral and brain development in both pathological and normal development. First, an animal model of schizophrenia is presented that suggests prenatal immune stimulation influences the postpubertal emergence of psychosis-related behavior in mice. Second, we describe a research program on infant rats that demonstrates how early odor learning has unique characteristics due to the unique functioning of the infant limbic system. Third, we present work on the rodent Octodon degus, which shows that early paternal and/or maternal deprivation alters development of limbic system synaptic density that corresponds to heightened emotionality. Fourth, ajuvenile model of stress is presented that suggests this developmental period is important in determining adulthood emotional well being. The approach of each research program is strikingly different, yet all succeed in delineating a specific aspect of early development and its effects on infant and adult outcome that expands our understanding of the developmental impact of infant experiences on emotional and limbic system development. Together, these research programs suggest that the developing organism’s developmental trajectory is influenced by environmental factors beginning in the fetus and extending through adolescence, although the specific timing and nature of the environmental influence has unique impact on adult mental health. PMID:17016842

Neurobiology of Aggression and Violence

PubMed Central

Siever, Larry J.

2014-01-01

Acts of violence account for an estimated 1.43 million deaths worldwide annually. While violence can occur in many contexts, individual acts of aggression account for the majority of instances. In some individuals, repetitive acts of aggression are grounded in an underlying neurobiological susceptibility that is just beginning to be understood. The failure of “top-down” control systems in the prefrontal cortex to modulate aggressive acts that are triggered by anger provoking stimuli appears to play an important role. An imbalance between prefrontal regulatory influences and hyper-responsivity of the amygdala and other limbic regions involved in affective evaluation are implicated. Insufficient serotonergic facilitation of “top-down” control, excessive catecholaminergic stimulation, and subcortical imbalances of glutamatergic/ gabaminergic systems as well as pathology in neuropeptide systems involved in the regulation of affiliative behavior may contribute to abnormalities in this circuitry. Thus, pharmacological interventions such as mood stabilizers, which dampen limbic irritability, or selective serotonin reuptake inhibitors (SSRIs), which may enhance “top-down” control, as well as psychosocial interventions to develop alternative coping skills and reinforce reflective delays may be therapeutic. PMID:18346997

[Proposal for a physiologic concept of thought based on the results of stereotaxic psychosurgery].

PubMed

Nádvorník, P; Pogády, J; Bernadic, M

2003-05-01

Authors have fifty years long experience with psychostereotactic surgery. On the bases of 209 operations of different types of mentally ill patients, authors built their own physiological conception of the central nervous system function. The new conception is described using block operators of thinking at the level of hypothalamus, limbic system, and neocortex in the hierarchic order. The basic physiological hypothalamic block contains two operators: stimulus evaluation and decision to act. Both operators together form reasonable, objective substantiation of thinking, which is transformed into psychological, subjective description at higher cerebral levels. New operator is added to the block diagram at the level of the limbic system: the choice of response base on experience stored in the high capacity memory. Vast neocortical memory creates a model of the individual world and it enables a new operator to be involved: prediction of the future events. Thinking, originally based on concrete images, is using abstract terms, subjected to the principles of grammar. Physiological basis of thinking enables the convergence of subjective and objective.

Paraneoplastic limbic encephalitis and possible narcolepsy in a patient with testicular cancer: case study.

PubMed Central

Landolfi, Joseph C.; Nadkarni, Mangala

2003-01-01

We describe a patient who presented with a clinical syndrome of limbic encephalitis, narcolepsy, and cataplexy. The anti-Ma2 antibody was positive. Although there was no mass on imaging, orchiectomy was performed in this patient, and testicular carcinoma was found. This is the first known case of limbic encephalitis and anti-Ma2 antibody to be associated with cataplexy and possible narcolepsy. Neurological symptoms precede the diagnosis of cancer in 50% of patients with paraneoplastic syndromes, and clinicians are therefore strongly advised to evaluate patients with neurological symptoms for this condition. PMID:12816728

The contribution of small vessel disease to subtypes of Alzheimer's disease: a study on cerebrospinal fluid and imaging biomarkers.

PubMed

Ferreira, Daniel; Shams, Sara; Cavallin, Lena; Viitanen, Matti; Martola, Juha; Granberg, Tobias; Shams, Mana; Aspelin, Peter; Kristoffersen-Wiberg, Maria; Nordberg, Agneta; Wahlund, Lars-Olof; Westman, Eric

2018-05-30

We investigated whether subtypes of Alzheimer's disease (AD), that is, typical, limbic-predominant, hippocampal-sparing, and minimal atrophy AD, had a specific signature of small vessel disease and neurodegeneration. Four hundred twenty-three clinically diagnosed AD patients were included (161 typical, 121 limbic-predominant, 70 hippocampal-sparing, 71 minimal atrophy). One hundred fifty-six fulfilled a biomarkers-based AD diagnosis. White matter hyperintensities and cerebral microbleeds (CMB) had the highest prevalence in limbic-predominant AD, and the lowest prevalence in minimal atrophy AD. CMB existed evenly in lobar and deep brain areas in limbic-predominant, typical, and hippocampal-sparing AD. In minimal atrophy AD, CMB were mainly located in brain lobar areas. Perivascular spaces in the centrum semiovale were more prevalent in typical AD. Small vessel disease contributed to the prediction of Mini-Mental State Examination. Minimal atrophy AD showed highly pathological levels of cerebrospinal fluid Aß 1-42 , total tau, and phosphorylated tau, in the absence of overt brain atrophy. Cerebral amyloid angiopathy seems to have a stronger contribution to hippocampal-sparing and minimal atrophy AD, whereas hypertensive arteriopathy may have a stronger contribution to typical and limbic-predominant AD. Copyright © 2018 Elsevier Inc. All rights reserved.

Localized disruption of Narp in medial prefrontal cortex blocks reinforcer devaluation performance

PubMed Central

Johnson, Alexander W.; Han, Sungho; Blouin, Ashley M.; Saini, Jasjit; Worley, Paul F.; During, Matthew J.; Holland, Peter C.; Baraban, Jay M.; Reti, Irving M.

2010-01-01

Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this localization pattern, Narp knockout mice show deficits in using the current value of a reinforcer to guide behavior, a critical function of the limbic system. To help assess whether this behavioral deficit is due to impairment of synaptogenesis during development or in modulating synaptic signaling in the mature brain, we have used a dominant negative Narp viral construct which blocks trafficking of endogenous Narp to axons. Focal injection of this viral construct into the medial prefrontal cortex (mPFC) of adult mice, a region containing Narp-positive projection neurons, blocked reinforcer devaluation. Thus, these results indicate that Narp released from mPFC neurons plays a key role in mediating synaptic changes underlying instrumental reinforcer devaluation. PMID:21127001

Déjà Vu Experiences in Healthy Czech Adults.

PubMed

Lacinová, Lenka; Neužilová Michalčáková, Radka; Širůček, Jan; Ježek, Stanislav; Chromec, Jakub; Masopustová, Zuzana; Urbánek, Tomáš; Brázdil, Milan

2016-12-01

The study examines the prevalence of déjà vu in healthy Czech adults and explores its relationships with a number of variables: age, sex, neuroticism, depression, the degree of irritability in the limbic system, perceived stress, and finally attachment avoidance and anxiety. The participants were 365 healthy adults ranging from 18 to 70 years recruited in the Czech Republic (mean age = 29.05; SD = 11.17) who filled out online questionnaires. Déjà vu experiences were reported by 324 (88.8%) of them. Persons who experienced déjà vu were younger than the persons who had not experienced it. We found that sex, levels of neuroticism, depression, perceived stress, and attachment did not serve as predictors of experiences of déjà vu phenomena. Finally, those who had reported déjà vu experiences reported more limbic system irritability symptoms. We discuss the possibility that déjà vu reports together with other studied variables mainly reflect the participants' willingness to report "extraordinal" experiences.

Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study

PubMed Central

Holschneider, Daniel P.; Wang, Zhuo; Pang, Raina D.

2014-01-01

Rodent cortical midline structures (CMS) are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC) remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [14C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow (CBF) was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas–findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways) will not only critically inform future work at the microscopic (single neurons and synapses) level, but also have translational value to advance our understanding of human brain architecture. PMID:24966831

Functional connectivity-based parcellation and connectome of cortical midline structures in the mouse: a perfusion autoradiography study.

PubMed

Holschneider, Daniel P; Wang, Zhuo; Pang, Raina D

2014-01-01

Rodent cortical midline structures (CMS) are involved in emotional, cognitive and attentional processes. Tract tracing has revealed complex patterns of structural connectivity demonstrating connectivity-based integration and segregation for the prelimbic, cingulate area 1, retrosplenial dysgranular cortices dorsally, and infralimbic, cingulate area 2, and retrosplenial granular cortices ventrally. Understanding of CMS functional connectivity (FC) remains more limited. Here we present the first subregion-level FC analysis of the mouse CMS, and assess whether fear results in state-dependent FC changes analogous to what has been reported in humans. Brain mapping using [(14)C]-iodoantipyrine was performed in mice during auditory-cued fear conditioned recall and in controls. Regional cerebral blood flow (CBF) was analyzed in 3-D images reconstructed from brain autoradiographs. Regions-of-interest were selected along the CMS anterior-posterior and dorsal-ventral axes. In controls, pairwise correlation and graph theoretical analyses showed strong FC within each CMS structure, strong FC along the dorsal-ventral axis, with segregation of anterior from posterior structures. Seed correlation showed FC of anterior regions to limbic/paralimbic areas, and FC of posterior regions to sensory areas-findings consistent with functional segregation noted in humans. Fear recall increased FC between the cingulate and retrosplenial cortices, but decreased FC between dorsal and ventral structures. In agreement with reports in humans, fear recall broadened FC of anterior structures to the amygdala and to somatosensory areas, suggesting integration and processing of both limbic and sensory information. Organizational principles learned from animal models at the mesoscopic level (brain regions and pathways) will not only critically inform future work at the microscopic (single neurons and synapses) level, but also have translational value to advance our understanding of human brain architecture.

Acute behavioral and EEG effects of NW-1015 on electrically-induced afterdischarge in conscious monkeys.

PubMed

Fariello, R G; Maj, R; Marrari, P; Beard, D; Algate, C; Salvati, P

2000-03-01

NW-1015 is a novel Na+ and Ca2+ channel blocker with broad spectrum anticonvulsant activity and an excellent safety margin. As the compound also shows sigma-1 receptor ligand properties it was deemed important to determine whether it possesses anticonvulsant properties in primates without causing behavioral and EEG abnormalities. Thus, the effects of NW-1015 on limbic electrically-induced afterdischarge (AD) were evaluated in four cynomolgus monkeys, and its activity compared to a single effective dose of phenytoin (PHT). The four male cynomolgus monkeys were chronically implanted for EEG recordings, from cortex and limbic structures. AD was induced in limbic areas by electrical stimulation. The effects of NW-1015 on the duration and the behavioral component of the AD were randomly tested at doses from 25 to 75 mg/kg and compared with the effects of PHT 50 mg/kg. Similarly to PHT, 50 mg/kg of NW-1015 significantly shortened the EEG AD and almost abolished AD elicited behavioral seizure. Only the behavioral effects of AD were reduced after administration of 25 mg/kg p.o. NW-1015 did not cause EEG or interictal behavioral alterations at doses up to 75 mg/kg p.o. These data further confirm the broad-spectrum anticonvulsant activity and a good safety profile of NW-1015 even in a primate model of complex partial seizures and suggest that its affinity for sigma-1 receptors is behaviorally irrelevant.

Morphological brain measures of cortico-limbic inhibition related to resilience.

PubMed

Gupta, Arpana; Love, Aubrey; Kilpatrick, Lisa A; Labus, Jennifer S; Bhatt, Ravi; Chang, Lin; Tillisch, Kirsten; Naliboff, Bruce; Mayer, Emeran A

2017-09-01

Resilience is the ability to adequately adapt and respond to homeostatic perturbations. Although resilience has been associated with positive health outcomes, the neuro-biological basis of resilience is poorly understood. The aim of the study was to identify associations between regional brain morphology and trait resilience with a focus on resilience-related morphological differences in brain regions involved in cortico-limbic inhibition. The relationship between resilience and measures of affect were also investigated. Forty-eight healthy subjects completed structural MRI scans. Self-reported resilience was measured using the Connor and Davidson Resilience Scale. Segmentation and regional parcellation of images was performed to yield a total of 165 regions. Gray matter volume (GMV), cortical thickness, surface area, and mean curvature were calculated for each region. Regression models were used to identify associations between morphology of regions belonging to executive control and emotional arousal brain networks and trait resilience (total and subscales) while controlling for age, sex, and total GMV. Correlations were also conducted between resilience scores and affect scores. Significant associations were found between GM changes in hypothesized brain regions (subparietal sulcus, intraparietal sulcus, amygdala, anterior mid cingulate cortex, and subgenual cingulate cortex) and resilience scores. There were significant positive correlations between resilience and positive affect and negative correlations with negative affect. Resilience was associated with brain morphology of regions involved in cognitive and affective processes related to cortico-limbic inhibition. Brain signatures associated with resilience may be a biomarker of vulnerability to disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Olfactory bulb dysgenesis, mirror neuron system dysfunction, and autonomic dysregulation as the neural basis for autism.

PubMed

Brang, David; Ramachandran, V S

2010-05-01

Autism is a disorder characterized by social withdrawal, impoverished language and empathy, and a profound inability to adopt another's viewpoint - a failure to construct a "theory of mind" for interpreting another person's thoughts and intentions. We previously showed that these symptoms might be explained, in part, by a paucity of mirror neurons. Prompted by an MRI report of an individual with autism, we now suggest that there may be, in addition, a congenital aplasia/dysplasia of the olfactory bulbs with consequent reduction of vasopressin and oxytocin receptor binding. There may also be sub-clinical temporal lobe epilepsy affecting the recently discovered third visual system that is rich in "empathy" related mirror neurons (MNS) and projects (via the TOP junction - just below the inferior parietal lobule) to limbic structures that regulate autonomic outflow. This causes deranged autonomic feedback, resulting in additional deficiencies in MNS with loss of emotional empathy and introspection.

Biological substrates of schizophrenia.

PubMed

Kovelman, J A; Scheibel, A B

1986-01-01

Schizophrenia is increasingly believed to represent a group of organic disorders which primarily, although not exclusively, affect the central nervous system. Our purpose is to review a representative sample of twentieth-century literature which speaks to the biological substrates of the syndrome. Subjects reviewed include genetic and environmental contributions to the onset of illness, early and recent findings of gross structural anomalies, and apparent histopathological alterations in cerebral cortex, cerebellar vermis, limbic system, and brain stem, as well as problems of cerebral asymmetry. Data from a diverse group of electrophysiological studies reveal several promising correlates of these areas of investigation. Despite the inconsistent nature of the findings to date, several themes have begun to emerge, including patterns of hypofrontal/hyperparietal regional cerebral flow and glucose utilization, left hemispheric dysfunction, and deficits of interhemispheric information processing. The interpretation and significance of these emerging patterns remains unclear and must await more profound insights into the nature of normal and abnormal cerebral function.

Herpes zoster chronification to postherpetic neuralgia induces brain activity and grey matter volume change

PubMed Central

Cao, Song; Qin, Bangyong; Zhang, Yi; Yuan, Jie; Fu, Bao; Xie, Peng; Song, Ganjun; Li, Ying; Yu, Tian

2018-01-01

Objective: Herpes zoster (HZ) can develop into postherpetic neuralgia (PHN), which is a chronic neuropathic pain (NP). Whether the chronification from HZ to PHN induced brain functional or structural change is unknown and no study compared the changes of the same brains of patients who transited from HZ to PHN. We minimized individual differences and observed whether the chronification of HZ to PHN induces functional and pain duration dependent grey matter volume (GMV) change in HZ-PHN patients. Methods: To minimize individual differences induced error, we enrolled 12 patients with a transition from HZ to PHN. The functional and structural changes of their brains between the two states were identified with resting-state functional MRI (rs-fMRI) technique (i.e., the regional homogeneity (ReHo) and fractional aptitude of low-frequency fluctuation (fALFF) method) and the voxel based morphometry (VBM) technology respectively. The correlations between MRI parameters (i.e., ΔReHo, ΔfALFF and ΔVBM) and Δpain duration were analyzed too. Results: Compared with HZ brains, PHN brains exhibited abnormal ReHo, fALFF and VBM values in pain matrix (the frontal lobe, parietal lobe, thalamus, limbic lobe and cerebellum) as well as the occipital lobe and temporal lobe. Nevertheless, the activity of vast area of cerebellum and frontal lobe significantly increased while that of occipital lobe and limbic lobe showed apparent decrease when HZ developed to PHN. In addition, PHN brain showed decreased GMV in the frontal lobe, the parietal lobe and the occipital lobe but increased in the cerebellum and the temporal lobe. Correlation analyses showed that some of the ReHo, fALFF and VBM differential areas (such as the cerebellum posterior lobe, the thalamus extra-nuclear and the middle temporal gyrus) correlated well with Δpain duration. Conclusions: HZ chronification induced functional and structural change in cerebellum, occipital lobe, temporal lobe, parietal lobe and limbic lobe. These changes may be correlated with HZ-PHN chronification. In addition, these changes could be reasons of refractory chronic pain of PHN. PMID:29423004

Factor analysis of regional brain activation in bipolar and healthy individuals reveals a consistent modular structure.

PubMed

Fleck, David E; Welge, Jeffrey A; Eliassen, James C; Adler, Caleb M; DelBello, Melissa P; Strakowski, Stephen M

2018-07-01

The neurophysiological substrates of cognition and emotion, as seen with fMRI, are generally explained using modular structures. The present study was designed to probe the modular structure of cognitive-emotional processing in bipolar and healthy individuals using factor analysis and compare the results with current conceptions of the neurophysiology of bipolar disorder. Exploratory factor analysis was used to assess patterns of covariation among brain regions-of-interest activated during the Continuous Performance Task with Emotional and Neutral Distractors in healthy and bipolar individuals without a priori constraints on the number or composition of latent factors. Results indicated a common cognitive-emotional network consisting of prefrontal, medial temporal, limbic, parietal, anterior cingulate and posterior cingulate modules. However, reduced brain activation to emotional stimuli in the frontal, medial temporal and limbic modules was apparent in the bipolar relative to the healthy group, potentially accounting for emotional dysregulation in bipolar disorder. This study is limited by a relatively small sample size recruited at a single site. The results have yet to be validated on a larger independent sample. Although the modular structure of cognitive-emotional processing is similar in bipolar and healthy individuals, activation in response to emotional/neutral cues varies. These findings are not only consistent with recent conceptions of mood regulation in bipolar disorder, but also suggest that regional activation can be considered within tighter modular structures without compromising data interpretation. This demonstration may serve as a template for data reduction in future region-of-interest analyses to increase statistical power. Copyright © 2018 Elsevier B.V. All rights reserved.

[The phenomenon of pain in the history of music – observations of neurobiological mechanisms of pain and its expressions in western music].

PubMed

Gasenzer, E R; Neugebauer, E A M

2014-12-01

Purpose of this essay is to provide a historical overview how music has dealt with the emotion and sensation of pain, as well as an overview over the more recent medical research into the relationship of music and pain. Since the beginnings of western music humans have put their emotions into musical sounds. During the baroque era, composers developed musical styles that expressed human emotions and our experiences of nature. In some compositions, like in operas, we find musical representations of pain. During Romanticism artists began to intrude into the soul of their audience. New expressive harmonies and styles touch the soul and the consciousness of the listener. With the inception of atonality dissonant sounds where experienced as a physical pain.The physiology of deep brain structures (like thalamus, hypothalamus or limbic system) and the physiology of the acoustic pathway process consonant and dissonant sound and musical perceptions in ways, that are similar to the perception of pain. In the thalamus and in the limbic system music and pain meet.The relationships of music and pain is a wide open research field with such interesting questions as the role of dopamine in the perception of consonant or dissonant music, or the processing of pain during music listening. Musicology has not yet embarked on a general investigation of how musical compositions express pain and how that has developed or changed over the centuries. Music therapy, neuro-musicology and the performing arts medicine are scientific fields that offer a lot of ideas for medical and musical research projects. © Georg Thieme Verlag KG Stuttgart · New York.

The anatomy of extended limbic pathways in Asperger syndrome: a preliminary diffusion tensor imaging tractography study.

PubMed

Pugliese, Luca; Catani, Marco; Ameis, Stephanie; Dell'Acqua, Flavio; Thiebaut de Schotten, Michel; Murphy, Clodagh; Robertson, Dene; Deeley, Quinton; Daly, Eileen; Murphy, Declan G M

2009-08-15

It has been suggested that people with autistic spectrum disorder (ASD) have altered development (and connectivity) of limbic circuits. However, direct evidence of anatomical differences specific to white matter pathways underlying social behaviour and emotions in ASD is lacking. We used Diffusion Tensor Imaging Tractography to compare, in vivo, the microstructural integrity and age-related differences in the extended limbic pathways between subjects with Asperger syndrome and healthy controls. Twenty-four males with Asperger syndrome (mean age 23+/-12 years, age range: 9-54 years) and 42 age-matched male controls (mean age 25+/-10 years, age range: 9-54 years) were studied. We quantified tract-specific diffusivity measurements as indirect indexes of microstructural integrity (e.g. fractional anisotropy, FA; mean diffusivity, MD) and tract volume (e.g. number of streamlines) of the main limbic tracts. The dissected limbic pathways included the inferior longitudinal fasciculus, inferior frontal occipital fasciculus, uncinate, cingulum and fornix. There were no significant between-group differences in FA and MD. However, compared to healthy controls, individuals with Asperger syndrome had a significantly higher number of streamlines in the right (p=.003) and left (p=.03) cingulum, and in the right (p=.03) and left (p=.04) inferior longitudinal fasciculus. In contrast, people with Asperger syndrome had a significantly lower number of streamlines in the right uncinate (p=.02). Within each group there were significant age-related differences in MD and number of streamlines, but not FA. However, the only significant age-related between-group difference was in mean diffusivity of the left uncinate fasciculus (Z(obs)=2.05) (p=.02). Our preliminary findings suggest that people with Asperger syndrome have significant differences in the anatomy, and maturation, of some (but not all) limbic tracts.

Hyporesponsive reward anticipation in the basal ganglia following severe institutional deprivation early in life.

PubMed

Mehta, Mitul A; Gore-Langton, Emma; Golembo, Nicole; Colvert, Emma; Williams, Steven C R; Sonuga-Barke, Edmund

2010-10-01

Severe deprivation in the first few years of life is associated with multiple difficulties in cognition and behavior. However, the brain basis for these difficulties is poorly understood. Structural and functional neuroimaging studies have implicated limbic system structures as dysfunctional, and one functional imaging study in a heterogeneous group of maltreated individuals has confirmed the presence of abnormalities in the basal ganglia. Based on these studies and known dopaminergic abnormalities from studies in experimental animals using social isolation, we used a task of monetary reward anticipation to examine the functional integrity of brain regions previously shown to be implicated in reward processing. Our sample included a group of adolescents (n = 12) who had experienced global deprivation early in their lives in Romania prior to adoption into UK families. In contrast to a nonadopted comparison group (n = 11), the adoptees did not recruit the striatum during reward anticipation despite comparable performance accuracy and latency. These results show, for the first time, an association between early institutional deprivation and brain reward systems in humans and highlight potential neural vulnerabilities resulting from such exposures.

A Neurobiological Model for the Effects of Early Brainstem Functioning on the Development of Behavior and Emotion Regulation in Infants: Implications for Prenatal and Perinatal Risk

ERIC Educational Resources Information Center

Geva, Ronny; Feldman, Ruth

2008-01-01

Neurobiological models propose an evolutionary, vertical-integrative perspective on emotion and behavior regulation, which postulates that regulatory functions are processed along three core brain systems: the brainstem, limbic, and cortical systems. To date, few developmental studies applied these models to research on prenatal and perinatal…

Outdoor Education Gives Fewer Demands for Action Regulation and an Increased Variability of Affordances

ERIC Educational Resources Information Center

Fiskum, Tove Anita; Jacobsen, Karl

2013-01-01

In children's lives there are a lot of instigators for actions in every milieu and situation. When children grow older, the cortical activity starts to regulate the action instigation from the limbic system. The school system makes demands of action regulation for children. In outdoor education the many instigators for actions are not under the…

The surface of the eye--a superficial entity with deep repercussions.

PubMed

Potop, Vasile; Dumitrache, Marieta; Ciocalteu, Alina

2009-01-01

The surface of the eye is an anatomical and functional entity with a relatively recent delimitation but with significant therapeutic and diagnostic consequences. The pathology of the conjunctive and cornea must be approached by looking at the interrelations between the two tissues that are so different anatomically and functionally but in the same time form a unit in structuring the eye's surface. There are two major categories of relations between the two tissues: one of them is mediated by lachrymal secretion, a process whose complexity is not yet fully understood, and the other is germinal, referring to the stem cells located at the limbus which become epithelial cornea cells that can fixate lachrymal fluid. Imbalances in the quantity and quality of lachrymal secretion can be compensated, up to a certain point, by artificial products, but in severe cases only specially prepared autologous serum can compensate the deficit. The limbic deficits that affect stem cells require complex therapeutic procedures like limbic cell transplant, using an amniotic membrane or autologous serum.

TRIMETHYLTIN DISRUPTS ACOUSTIC STARTLE RESPONDING IN ADULT RATS

EPA Science Inventory

Trimethyltin (TMT) is a limbic-system toxicant which also produces sensory dysfunction in adult animals. In the present experiment, the authors examined the effects of TMT on the acoustic startle response. Adult male, Long-Evans rats (N=12/dose) received a single i.p. injection o...

Pathology of domoic acid toxicity in California sea lions (Zalophus californianus).

PubMed

Silvagni, P A; Lowenstine, L J; Spraker, T; Lipscomb, T P; Gulland, F M D

2005-03-01

Over 100 free-ranging adult California sea lions (Zalophus californianus) and one Northern fur seal (Callorhinus ursinus), predominantly adult females, were intoxicated by domoic acid (DA) during three harmful algal blooms between 1998 and 2000 in central and northern California coastal waters. The vector prey item was Northern anchovy (Engraulis mordax) and the primary DA-producing algal diatom was Psuedonitzschia australis. Postmortem examination revealed gross and histologic findings that were distinctive and aided in diagnosis. A total of 109 sea lions were examined, dying between 1 day and 10 months after admission to a marine mammal rehabilitation center. Persistent seizures with obtundation were the main clinical findings. Frequent gross findings in animals dying acutely consisted of piriform lobe malacia, myocardial pallor, bronchopneumonia, and complications related to pregnancy. Gross findings in animals dying months after intoxication included bilateral hippocampal atrophy. Histologic observations implicated limbic system seizure injury consistent with excitotoxin exposure. Peracutely, there was microvesicular hydropic degeneration within the neuropil of the hippocampus, amygdala, pyriform lobe, and other limbic structures. Acutely, there was ischemic neuronal necrosis, particularly apparent in the granular cells of the dentate gyrus and the pyramidal cells within the hippocampus cornu ammonis (CA) sectors CA4, CA3, and CA1. Dentate granular cell necrosis has not been reported in human or experimental animal DA toxicity and may be unique to sea lions. Chronically, there was gliosis, mild nonsuppurative inflammation, and loss of laminar organization in affected areas.

Abnormal fronto-limbic engagement in incarcerated stimulant users during moral processing.

PubMed

Fede, Samantha J; Harenski, Carla L; Schaich Borg, Jana; Sinnott-Armstrong, Walter; Rao, Vikram; Caldwell, Brendan M; Nyalakanti, Prashanth K; Koenigs, Michael R; Decety, Jean; Calhoun, Vince D; Kiehl, Kent A

2016-09-01

Stimulant use is a significant and prevalent problem, particularly in criminal populations. Previous studies found that cocaine and methamphetamine use is related to impairment in identifying emotions and empathy. Stimulant users also have abnormal neural structure and function of the ventromedial prefrontal cortex (vmPFC), amygdala, and anterior (ACC) and posterior cingulate (PCC), regions implicated in moral decision-making. However, no research has studied the neural correlates of stimulant use and explicit moral processing in an incarcerated population. Here, we examine how stimulant use affects sociomoral processing that might contribute to antisocial behavior. We predicted that vmPFC, amygdala, PCC, and ACC would show abnormal neural response during a moral processing task in incarcerated methamphetamine and cocaine users. Incarcerated adult males (N = 211) were scanned with a mobile MRI system while completing a moral decision-making task. Lifetime drug use was assessed. Neural responses during moral processing were compared between users and non-users. The relationship between duration of use and neural function was also examined. Incarcerated stimulant users showed less amygdala engagement than non-users during moral processing. Duration of stimulant use was negatively associated with activity in ACC and positively associated with vmPFC response during moral processing. These results suggest a dynamic pattern of fronto-limbic moral processing related to stimulant use with deficits in both central motive and cognitive integration elements of biological moral processes theory. This increases our understanding of how drug use relates to moral processing in the brain in an ultra-high-risk population.

Consciousness and epilepsy: why are complex-partial seizures complex?

PubMed Central

Englot, Dario J.; Blumenfeld, Hal

2010-01-01

Why do complex-partial seizures in temporal lobe epilepsy (TLE) cause a loss of consciousness? Abnormal function of the medial temporal lobe is expected to cause memory loss, but it is unclear why profoundly impaired consciousness is so common in temporal lobe seizures. Recent exciting advances in behavioral, electrophysiological, and neuroimaging techniques spanning both human patients and animal models may allow new insights into this old question. While behavioral automatisms are often associated with diminished consciousness during temporal lobe seizures, impaired consciousness without ictal motor activity has also been described. Some have argued that electrographic lateralization of seizure activity to the left temporal lobe is most likely to cause impaired consciousness, but the evidence remains equivocal. Other data correlates ictal consciousness in TLE with bilateral temporal lobe involvement of seizure spiking. Nevertheless, it remains unclear why bilateral temporal seizures should impair responsiveness. Recent evidence has shown that impaired consciousness during temporal lobe seizures is correlated with large-amplitude slow EEG activity and neuroimaging signal decreases in the frontal and parietal association cortices. This abnormal decreased function in the neocortex contrasts with fast polyspike activity and elevated cerebral blood flow in limbic and other subcortical structures ictally. Our laboratory has thus proposed the “network inhibition hypothesis,” in which seizure activity propagates to subcortical regions necessary for cortical activation, allowing the cortex to descend into an inhibited state of unconsciousness during complex-partial temporal lobe seizures. Supporting this hypothesis, recent rat studies during partial limbic seizures have shown that behavioral arrest is associated with frontal cortical slow waves, decreased neuronal firing, and hypometabolism. Animal studies further demonstrate that cortical deactivation and behavioral changes depend on seizure spread to subcortical structures including the lateral septum. Understanding the contributions of network inhibition to impaired consciousness in TLE is an important goal, as recurrent limbic seizures often result in cortical dysfunction during and between epileptic events that adversely affects patients’ quality of life. PMID:19818900

Nicotine Modulates Multiple Regions in the Limbic Stress Network Regulating Activation of Hypophysiotrophic Neurons in Hypothalamic Paraventricular Nucleus

PubMed Central

Yu, Guoliang; Sharp, Burt M.

2012-01-01

Nicotine intake affects CNS responses to stressors. We reported that nicotine self-administration (SA) augmented the hypothalamo-pituitary-adrenal (HPA) stress response, in part due to altered neurotransmission and neuropeptide expression within hypothalamic paraventricular nucleus (PVN). Limbic-PVN interactions involving medial prefrontal cortex, amygdala, bed nucleus of the stria terminalis (BST) greatly impact the HPA stress response. Therefore, we investigated the effects of nicotine SA on stress-induced neuronal activation in limbic-PVN network, using c-Fos protein immunohistochemistry and retrograde tracing. Nicotine decreased stress-induced c-Fos in prelimbic cortex (PrL), anteroventral BST (avBST), and peri-PVN; but increased c-Fos induction in medial amygdala (MeA), locus coeruleus, and PVN. Fluoro-gold (FG) was injected into avBST or PVN, since GABAergic neurons in avBST projecting to PVN corticotrophin-releasing factor (CRF) neurons relay information from both PrL glutamatergic and MeA GABAergic neurons. The stress-induced c-Fos expression in retrograde-labeled FG+ neurons was decreased in PrL by nicotine, but increased in MeA, and also reduced in avBST. Therefore, within limbic-PVN network, nicotine SA exerts selective regional effects on neuronal activation by stress. These findings expand the mechanistic framework by demonstrating altered limbic-BST-PVN interactions underlying the disinhibition of PVN CRF neurons, an essential component of the amplified HPA response to stress by nicotine. PMID:22578217

Abnormal Functional Connectivity in Autism Spectrum Disorders during Face Processing

ERIC Educational Resources Information Center

Kleinhans, Natalia M.; Richards, Todd; Sterling, Lindsey; Stegbauer, Keith C.; Mahurin, Roderick; Johnson, L. Clark; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth

2008-01-01

Abnormalities in the interactions between functionally linked brain regions have been suggested to be associated with the clinical impairments observed in autism spectrum disorders (ASD). We investigated functional connectivity within the limbic system during face identification; a primary component of social cognition, in 19 high-functioning…

Creating an Expressive Performance Mindset

ERIC Educational Resources Information Center

Broomhead, Paul; Skidmore, Jon B.

2014-01-01

Students in performance situations sometimes experience physiological symptoms that inhibit their ability to perform as expressively as they otherwise might possess the understanding and ability to do. As students set out to perform with an expressive mindset, the brain's limbic system may detect some perceived danger in the situation and…

Localized Disruption of Narp in Medial Prefrontal Cortex Blocks Reinforcer Devaluation Performance

ERIC Educational Resources Information Center

Johnson, Alexander W.; Han, Sungho; Blouin, Ashley M.; Saini, Jasjit; Worley, Paul F.; During, Matthew J.; Holland, Peter C.; Baraban, Jay M.; Reti, Irving M.

2010-01-01

Neuronal activity regulated pentraxin (Narp) is a secreted protein that regulates [alpha]-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPAR) aggregation and synaptogenesis. Mapping of Narp-positive neurons in brain has revealed it is prominently expressed in several limbic system projection pathways. Consistent with this…

Cognition in Domestic Dogs: Object Permanence & Social Cueing

ERIC Educational Resources Information Center

Clotfelter, Ethan D.; Hollis, Karen L.

2008-01-01

Cognition is a general term describing the mental capacities of an animal, and often includes the ability to categorize, remember, and communicate about objects in the environment. Numerous regions of the telencephalon (cerebral cortex and limbic system) are responsible for these cognitive functions. Although many researchers have used traditional…

Loss of hippocampal serine protease BSP1/neuropsin predisposes to global seizure activity.

PubMed

Davies, B; Kearns, I R; Ure, J; Davies, C H; Lathe, R

2001-09-15

Serine proteases in the adult CNS contribute both to activity-dependent structural changes accompanying learning and to the regulation of excitotoxic cell death. Brain serine protease 1 (BSP1)/neuropsin is a trypsin-like serine protease exclusively expressed, within the CNS, in the hippocampus and associated limbic structures. To explore the role of this enzyme, we have used gene targeting to disrupt this gene in mice. Mutant mice were viable and overtly normal; they displayed normal hippocampal long-term synaptic potentiation (LTP) and exhibited no deficits in spatial navigation (water maze). Nevertheless, electrophysiological studies revealed that the hippocampus of mice lacking this specifically expressed protease possessed an increased susceptibility for hyperexcitability (polyspiking) in response to repetitive afferent stimulation. Furthermore, seizure activity on kainic acid administration was markedly increased in mutant mice and was accompanied by heightened immediate early gene (c-fos) expression throughout the brain. In view of the regional selectivity of BSP1/neuropsin brain expression, the observed phenotype may selectively reflect limbic function, further implicating the hippocampus and amygdala in controlling cortical activation. Within the hippocampus, our data suggest that BSP1/neuropsin, unlike other serine proteases, has little effect on physiological synaptic remodeling and instead plays a role in limiting neuronal hyperexcitability induced by epileptogenic insult.

Retention of identity versus expression of emotional faces differs in the recruitment of limbic areas.

PubMed

Röder, Christian H; Mohr, Harald; Linden, David E J

2011-02-01

Faces are multidimensional stimuli that convey information for complex social and emotional functions. Separate neural systems have been implicated in the recognition of facial identity (mainly extrastriate visual cortex) and emotional expression (limbic areas and the superior temporal sulcus). Working-memory (WM) studies with faces have shown different but partly overlapping activation patterns in comparison to spatial WM in parietal and prefrontal areas. However, little is known about the neural representations of the different facial dimensions during WM. In the present study 22 subjects performed a face-identity or face-emotion WM task at different load levels during functional magnetic resonance imaging. We found a fronto-parietal-visual WM-network for both tasks during maintenance, including fusiform gyrus. Limbic areas in the amygdala and parahippocampal gyrus demonstrated a stronger activation for the identity than the emotion condition. One explanation for this finding is that the repetitive presentation of faces with different identities but the same emotional expression during the identity-task is responsible for the stronger increase in BOLD signal in the amygdala. These results raise the question how different emotional expressions are coded in WM. Our findings suggest that emotional expressions are re-coded in an abstract representation that is supported at the neural level by the canonical fronto-parietal WM network. Copyright © 2010 Elsevier Ltd. All rights reserved.

Preferential suppression of limbic Fos expression by intermittent hypoxia in obese diabetic mice.

PubMed

Mukai, Takahiro; Nagao, Yuki; Nishioka, Satoshi; Hayashi, Tetsuya; Shimizu, Saki; Ono, Asuka; Sakagami, Yoshihisa; Watanabe, Sho; Ueda, Yoko; Hara, Madoka; Tokudome, Kentaro; Kato, Ryuji; Matsumura, Yasuo; Ohno, Yukihiro

2013-12-01

Sleep apnea (SA) causes not only sleep disturbances, but also neurocognitive impairments and/or psychoemotional disorders. Here, we studied the effects of intermittent hypoxia (IH) on forebrain Fos expression using obese diabetic db/db mice to explore the pathophysiological alterations in neural activities and the brain regions related to SA syndrome. Male db/db mice were exposed to IH stimuli (repetitive 6-min cycles of 1min with 5% oxygen followed by 5min with 21% oxygen) for 8h (80 cycles) per day or normoxic condition (control group) for 14 days. Fos protein expression was immunohistochemically examined a day after the last IH exposure. Mapping analysis revealed a significant reduction of Fos expression by IH in limbic and paralimbic structures, including the cingulate and piriform cortices, the core part of the nucleus accumbens and most parts of the amygdala (i.e., the basolateral and basomedial amygdaloid nuclei, cortical amygdaloid area and medial amygdaloid nucleus). In the brain stem regions, Fos expression was region-specifically reduced in the ventral tegmental area while other regions including the striatum, thalamus and hypothalamus, were relatively resistant against IH. In addition, db/db mice exposed to IH showed a trend of sedative and/or depressive behavioral signs in the open field and forced swim tests. The present results illustrate that SA in the obese diabetic model causes neural suppression preferentially in the limbic and paralimbic regions, which may be related to the neuropsychological disturbances associated with SA. Copyright © 2013. Published by Elsevier Ireland Ltd.

Right Limbic FDG-PET Hypometabolism Correlates with Emotion Recognition and Attribution in Probable Behavioral Variant of Frontotemporal Dementia Patients

PubMed Central

Cerami, Chiara; Dodich, Alessandra; Iannaccone, Sandro; Marcone, Alessandra; Lettieri, Giada; Crespi, Chiara; Gianolli, Luigi; Cappa, Stefano F.; Perani, Daniela

2015-01-01

The behavioural variant of frontotemporal dementia (bvFTD) is a rare disease mainly affecting the social brain. FDG-PET fronto-temporal hypometabolism is a supportive feature for the diagnosis. It may also provide specific functional metabolic signatures for altered socio-emotional processing. In this study, we evaluated the emotion recognition and attribution deficits and FDG-PET cerebral metabolic patterns at the group and individual levels in a sample of sporadic bvFTD patients, exploring the cognitive-functional correlations. Seventeen probable mild bvFTD patients (10 male and 7 female; age 67.8±9.9) were administered standardized and validated version of social cognition tasks assessing the recognition of basic emotions and the attribution of emotions and intentions (i.e., Ekman 60-Faces test-Ek60F and Story-based Empathy task-SET). FDG-PET was analysed using an optimized voxel-based SPM method at the single-subject and group levels. Severe deficits of emotion recognition and processing characterized the bvFTD condition. At the group level, metabolic dysfunction in the right amygdala, temporal pole, and middle cingulate cortex was highly correlated to the emotional recognition and attribution performances. At the single-subject level, however, heterogeneous impairments of social cognition tasks emerged, and different metabolic patterns, involving limbic structures and prefrontal cortices, were also observed. The derangement of a right limbic network is associated with altered socio-emotional processing in bvFTD patients, but different hypometabolic FDG-PET patterns and heterogeneous performances on social tasks at an individual level exist. PMID:26513651

Altered connections on the road to psychopathy.

PubMed

Craig, M C; Catani, M; Deeley, Q; Latham, R; Daly, E; Kanaan, R; Picchioni, M; McGuire, P K; Fahy, T; Murphy, D G M

2009-10-01

Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, however, has ever studied the white matter connections (such as the uncinate fasciculus (UF)) linking these structures in psychopaths. Therefore, we used in vivo diffusion tensor magnetic resonance imaging (DT-MRI) tractography to analyse the microstructural integrity of the UF in psychopaths (defined by a Psychopathy Checklist Revised (PCL-R) score of > or = 25) with convictions that included attempted murder, manslaughter, multiple rape with strangulation and false imprisonment. We report significantly reduced fractional anisotropy (FA) (P<0.003), an indirect measure of microstructural integrity, in the UF of psychopaths compared with age- and IQ-matched controls. We also found, within psychopaths, a correlation between measures of antisocial behaviour and anatomical differences in the UF. To confirm that these findings were specific to the limbic amygdala-OFC network, we also studied two 'non-limbic' control tracts connecting the posterior visual and auditory areas to the amygdala and the OFC, and found no significant between-group differences. Lastly, to determine that our findings in UF could not be totally explained by non-specific confounds, we carried out a post hoc comparison with a psychiatric control group with a past history of drug abuse and institutionalization. Our findings remained significant. Taken together, these results suggest that abnormalities in a specific amygdala-OFC limbic network underpin the neurobiological basis of psychopathy.

Mapping the Primate Visual System with [2-14C]Deoxyglucose

NASA Astrophysics Data System (ADS)

Macko, Kathleen A.; Jarvis, Charlene D.; Kennedy, Charles; Miyaoka, Mikoto; Shinohara, Mami; Sokoloff, Louis; Mishkin, Mortimer

1982-10-01

The [2-14C]deoxyglucose method was used to identify the cerebral areas related to vision in the rhesus monkey (Macaca mulatta). This was achieved by comparing glucose utilization in a visually stimulated with that in a visually deafferented hemisphere. The cortical areas related to vision included the entire expanse of striate, prestriate, and inferior temporal cortex as far forward as the temporal pole, the posterior part of the inferior parietal lobule, and the prearcuate and inferior prefrontal cortex. Subcortically, in addition to the dorsal lateral geniculate nucleus and superficial layers of the superior colliculus, the structures related to vision included large parts of the pulvinar, caudate, putamen, claustrum, and amygdala. These results, which are consonant with a model of visual function that postulates an occipito-temporo-prefrontal pathway for object vision and an occipito-parieto-prefrontal pathway for spatial vision, reveal the full extent of those pathways and identify their points of contact with limbic, striatal, and diencephalic structures.

Structural bases for neurophysiological investigations of amygdaloid complex of the brain

NASA Astrophysics Data System (ADS)

Kalimullina, Liliya B.; Kalkamanov, Kh. A.; Akhmadeev, Azat V.; Zakharov, Vadim P.; Sharafullin, Ildus F.

2015-11-01

Amygdala (Am) as a part of limbic system of the brain defines such important functions as adaptive behavior of animals, formation of emotions and memory, regulation of endocrine and visceral functions. We worked out, with the help of mathematic modelling of the pattern recognition theory, principles for organization of neurophysiological and neuromorphological studies of Am nuclei, which take into account the existing heterogeneity of its formations and optimize, to a great extent, the protocol for carrying out of such investigations. The given scheme of studies of Am’s structural-functional organization at its highly-informative sections can be used as a guide for precise placement of electrodes’, cannulae’s and microsensors into particular Am nucleus in the brain with the registration not only the nucleus itself, but also its extensions. This information is also important for defining the number of slices covering specific Am nuclei which must be investigated to reveal the physiological role of a particular part of amygdaloid complex.

The Basolateral Amygdala and Nucleus Accumbens Core Mediate Dissociable Aspects of Drug Memory Reconsolidation

ERIC Educational Resources Information Center

Theberge, Florence R. M.; Milton, Amy L.; Belin, David; Lee, Jonathan L. C.; Everitt, Barry J.

2010-01-01

A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory reconsolidation is unclear. The aim…

[Anti-Ma2, anti-NMDA-receptor and anti-GluRε2 limbic encephalitis with testicular seminoma: short-term memory disturbance].

PubMed

Kubota, Akihiro; Tajima, Takashi; Narukawa, Shinya; Yamazato, Masamizu; Fukaura, Hikoaki; Takahashi, Yukitoshi; Tanaka, Keiko; Shimizu, Jun; Nomura, Kyoichi

2012-01-01

A 36-year-old man presented with cognitive impairment and disturbance of short-term memory functions with character change. Cerebrospinal fluid analysis revealed no abnormalities; however, brain MRI revealed high-signal intensity from bilateral hippocampus lesions on fluid attenuated inversion recovery (FLAIR) images and T(2) weighted images. The 18F-fluorodeoxyglucose PET demonstrated high glucose uptake in the bilateral hippocampus lesions. He was diagnosed as limbic encephalitis, and was administered high-dose intravenous methylprednisolone and immune adsorption plasma therapy followed by intravenous immunoglobulin therapy. MRI abnormalities improved after treatment but recent memory disturbance remained. Ma2 antibody, NMDA-receptor antibody, and GluRε2 antibody were positive. Eleven months atter the onset of disease, the tumor was identified in left testicle by ultrasound and removed the tumor. The pathological findings were seminoma. We experienced a case of paraneoplastic limbic encephalitis associated with seminoma with short-term memory disturbance. The occurrence of paraneoplastic limbic encephalitis with antibodies against cell membrane (NMDA-receptor antibody and GluRε2 antibody) and intracellular (Ma2 antibody) is rare even in the literature.

Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.

PubMed

Thyrion, Lisa; Raedt, Robrecht; Portelli, Jeanelle; Van Loo, Pieter; Wadman, Wytse J; Glorieux, Griet; Lambrecht, Bart N; Janssens, Sophie; Vonck, Kristl; Boon, Paul

2016-03-01

Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in seizure generation. This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100 min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Taken together, our results consistently show that uric acid is released during limbic seizures and suggest that uric acid facilitates seizure generalization. Copyright © 2016 Elsevier Inc. All rights reserved.

Systematic review of the neural basis of social cognition in patients with mood disorders.

PubMed

Cusi, Andrée M; Nazarov, Anthony; Holshausen, Katherine; Macqueen, Glenda M; McKinnon, Margaret C

2012-05-01

This review integrates neuroimaging studies of 2 domains of social cognition--emotion comprehension and theory of mind (ToM)--in patients with major depressive disorder and bipolar disorder. The influence of key clinical and method variables on patterns of neural activation during social cognitive processing is also examined. Studies were identified using PsycINFO and PubMed (January 1967 to May 2011). The search terms were "fMRI," "emotion comprehension," "emotion perception," "affect comprehension," "affect perception," "facial expression," "prosody," "theory of mind," "mentalizing" and "empathy" in combination with "major depressive disorder," "bipolar disorder," "major depression," "unipolar depression," "clinical depression" and "mania." Taken together, neuroimaging studies of social cognition in patients with mood disorders reveal enhanced activation in limbic and emotion-related structures and attenuated activity within frontal regions associated with emotion regulation and higher cognitive functions. These results reveal an overall lack of inhibition by higher-order cognitive structures on limbic and emotion-related structures during social cognitive processing in patients with mood disorders. Critically, key variables, including illness burden, symptom severity, comorbidity, medication status and cognitive load may moderate this pattern of neural activation. Studies that did not include control tasks or a comparator group were included in this review. Further work is needed to examine the contribution of key moderator variables and to further elucidate the neural networks underlying altered social cognition in patients with mood disorders. The neural networks under lying higher-order social cognitive processes, including empathy, remain unexplored in patients with mood disorders.

Nicotine modulates multiple regions in the limbic stress network regulating activation of hypophysiotrophic neurons in hypothalamic paraventricular nucleus.

PubMed

Yu, Guoliang; Sharp, Burt M

2012-08-01

Nicotine intake affects CNS responses to stressors. We reported that nicotine self-administration (SA) augmented the hypothalamo-pituitary-adrenal (HPA) stress response, in part because of the altered neurotransmission and neuropeptide expression within hypothalamic paraventricular nucleus (PVN). Limbic-PVN interactions involving medial prefrontal cortex, amygdala, and bed nucleus of the stria terminalis (BST) greatly impact the HPA stress response. Therefore, we investigated the effects of nicotine SA on stress-induced neuronal activation in limbic-PVN network, using c-Fos protein immunohistochemistry and retrograde tracing. Nicotine decreased stress-induced c-Fos in prelimbic cortex (PrL), anteroventral BST (avBST), and peri-PVN, but increased c-Fos induction in medial amygdala (MeA), locus coeruleus, and PVN. Fluoro-gold (FG) was injected into avBST or PVN, as GABAergic neurons in avBST projecting to PVN corticotrophin-releasing factor neurons relay information from both PrL glutamatergic and MeA GABAergic neurons. The stress-induced c-Fos expression in retrograde-labeled FG+ neurons was decreased in PrL by nicotine, but increased in MeA, and also reduced in avBST. Therefore, within limbic-PVN network, nicotine SA exerts selective regional effects on neuronal activation by stress. These findings expand the mechanistic framework by demonstrating altered limbic-BST-PVN interactions underlying the disinhibition of PVN corticotrophin-releasing factor neurons, an essential component of the amplified HPA response to stress by nicotine. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

The neuropeptide-12 improves recognition memory and neuronal plasticity of the limbic system in old rats.

PubMed

Hernández-Hernández, Elizabeth Monserrat; Caporal Hernandez, Karen; Vázquez-Roque, Rubén Antonio; Díaz, Alfonso; de la Cruz, Fidel; Florán, Benjamin; Flores, Gonzalo

2018-08-01

Aging is a stage of life where cognitive and motor functions are impaired. This is because oxidative and inflammatory processes exacerbate neurodegeneration, which affects dendritic morphology and neuronal communication of limbic regions with memory loss. Recently, the use of trophic substances has been proposed to prevent neuronal deterioration. The neuropeptide-12 (N-PEP-12) has been evaluated in elderly patients with dementia, showing improvements in cognitive tasks due to acts as a neurotrophic factor. In the present work, we evaluated the effect of N-PEP-12 on motor activity and recognition memory, as well as its effects on dendritic morphology and the immunoreactivity of GFAP, Synaptophysin (SYP), and BDNF in neurons of the prefrontal cortex (PFC), dorsal hippocampus (DH) and nucleus accumbens (NAcc) of aged rats. The results show that N-PEP-12 improved the recognition memory, but the motor activity was not modified compared to the control animals. N-PEP-12 increases the density of dendritic spines and the total dendritic length in neurons of the PFC (layers 3 and 5) and in DH (CA1 and CA3). Interestingly NAcc neurons showed a reduction in the number of dendritic spines. In the N-PEP-12 animals, when evaluating the immunoreactivity for SYP and BDNF, there was an increase in the three brain regions, while the mark for GFAP decreased significantly. Our results suggest that N-PEP-12 promotes neuronal plasticity in the limbic system of aged animals, which contributes to improving recognition memory. In this sense, N-PEP-12 can be considered as a pharmacological alternative to prevent or delay brain aging and control senile dementias. © 2018 Wiley Periodicals, Inc.

Patterns of thought: Population variation in the associations between large-scale network organisation and self-reported experiences at rest.

PubMed

Wang, Hao-Ting; Bzdok, Danilo; Margulies, Daniel; Craddock, Cameron; Milham, Michael; Jefferies, Elizabeth; Smallwood, Jonathan

2018-08-01

Contemporary cognitive neuroscience recognises unconstrained processing varies across individuals, describing variation in meaningful attributes, such as intelligence. It may also have links to patterns of on-going experience. This study examined whether dimensions of population variation in different modes of unconstrained processing can be described by the associations between patterns of neural activity and self-reports of experience during the same period. We selected 258 individuals from a publicly available data set who had measures of resting-state functional magnetic resonance imaging, and self-reports of experience during the scan. We used machine learning to determine patterns of association between the neural and self-reported data, finding variation along four dimensions. 'Purposeful' experiences were associated with lower connectivity - in particular default mode and limbic networks were less correlated with attention and sensorimotor networks. 'Emotional' experiences were associated with higher connectivity, especially between limbic and ventral attention networks. Experiences focused on themes of 'personal importance' were associated with reduced functional connectivity within attention and control systems. Finally, visual experiences were associated with stronger connectivity between visual and other networks, in particular the limbic system. Some of these patterns had contrasting links with cognitive function as assessed in a separate laboratory session - purposeful thinking was linked to greater intelligence and better abstract reasoning, while a focus on personal importance had the opposite relationship. Together these findings are consistent with an emerging literature on unconstrained states and also underlines that these states are heterogeneous, with distinct modes of population variation reflecting the interplay of different large-scale networks. Copyright © 2018 Elsevier Inc. All rights reserved.

Functional alterations of fronto-limbic circuit and default mode network systems in first-episode, drug-naïve patients with major depressive disorder: A meta-analysis of resting-state fMRI data.

PubMed

Zhong, Xue; Pu, Weidan; Yao, Shuqiao

2016-12-01

The neurobiological mechanisms of depression are increasingly being explored through resting-state brain imaging studies. However, resting-state fMRI findings have varied, perhaps because of differences between study populations, which included the disorder course and medication use. The aim of our study was to integrate studies of resting-state fMRI and explore the alterations of abnormal brain activity in first-episode, drug-naïve patients with major depressive disorder. Relevant imaging reports in English were searched, retrieved, selected and subjected to analysis by activation likelihood estimation, a coordinate-based meta-analysis technique (final sample, 31 studies). Coordinates extracted from the original reports were assigned to two categories based on effect directionality. Compared with healthy controls, the first-episode, medication-naïve major depressive disorder patients showed decreased brain activity in the dorsolateral prefrontal cortex, superior temporal gyrus, posterior precuneus, and posterior cingulate, as well as in visual areas within the occipital lobe, lingual gyrus, and fusiform gyrus, and increased activity in the putamen and anterior precuneus. Not every study that has reported relevant data met the inclusion criteria. Resting-state functional alterations were located mainly in the fronto-limbic system, including the dorsolateral prefrontal cortex and putamen, and in the default mode network, namely the precuneus and superior/middle temporal gyrus. Abnormal functional alterations of the fronto-limbic circuit and default mode network may be characteristic of first-episode, drug-naïve major depressive disorder patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Acupuncture, the limbic system, and the anticorrelated networks of the brain.

PubMed

Hui, Kathleen K S; Marina, Ovidiu; Liu, Jing; Rosen, Bruce R; Kwong, Kenneth K

2010-10-28

The study of the mechanism of acupuncture action was revolutionized by the use of functional magnetic resonance imaging (fMRI). Over the past decade, our fMRI studies of healthy subjects have contributed substantially to elucidating the central effect of acupuncture on the human brain. These studies have shown that acupuncture stimulation, when associated with sensations comprising deqi, evokes deactivation of a limbic-paralimbic-neocortical network, which encompasses the limbic system, as well as activation of somatosensory brain regions. These networks closely match the default mode network and the anti-correlated task-positive network described in the literature. We have also shown that the effect of acupuncture on the brain is integrated at multiple levels, down to the brainstem and cerebellum. Our studies support the hypothesis that the effect of acupuncture on the brain goes beyond the effect of attention on the default mode network or the somatosensory stimulation of acupuncture needling. The amygdala and hypothalamus, in particular, show decreased activation during acupuncture stimulation that is not commonly associated with default mode network activity. At the same time, our research shows that acupuncture stimulation needs to be done carefully, limiting stimulation when the resulting sensations are very strong or when sharp pain is elicited. When acupuncture induced sharp pain, our studies show that the deactivation was attenuated or reversed in direction. Our results suggest that acupuncture mobilizes the functionally anti-correlated networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response. In this work we also discuss multiple avenues of future research, including the role of neurotransmitters, the effect of different acupuncture techniques, and the potential clinical application of our research findings to disease states including chronic pain, major depression, schizophrenia, autism, and Alzheimer's disease. Published by Elsevier B.V.

Hippocampal TNFα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy.

PubMed

Patel, Dipan C; Wallis, Glenna; Dahle, E Jill; McElroy, Pallavi B; Thomson, Kyle E; Tesi, Raymond J; Szymkowski, David E; West, Peter J; Smeal, Roy M; Patel, Manisha; Fujinami, Robert S; White, H Steve; Wilcox, Karen S

2017-01-01

Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler's murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures. We found a significant increase in both mRNA and protein levels of TNFα and the protein expression ratio of TNF receptors (TNFR1:TNFR2) in the hippocampus, a brain region most likely involved in seizure initiation, after TMEV infection, which suggests that TNFα signaling, predominantly through TNFR1, may contribute to limbic hyperexcitability. An increase in hippocampal cell-surface glutamate receptor expression was also observed during acute seizures. Although pharmacological inhibition of TNFR1-mediated signaling had no effect on acute seizures, several lines of genetically modified animals deficient in either TNFα or TNFRs had robust changes in seizure incidence and severity after TMEV infection. TNFR2 -/- mice were highly susceptible to developing acute seizures, suggesting that TNFR2-mediated signaling may provide beneficial effects during the acute seizure period. Taken together, the present results suggest that inflammation in the hippocampus, caused predominantly by TNFα signaling, contributes to hyperexcitability and acute seizures after TMEV infection. Pharmacotherapies designed to suppress TNFR1-mediated or augment TNFR2-mediated effects of TNFα may provide antiseizure and disease-modifying effects after central nervous system infection.

Hippocampal TNFα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy

PubMed Central

Patel, Dipan C.; Wallis, Glenna; Dahle, E. Jill; McElroy, Pallavi B.; Thomson, Kyle E.; West, Peter J.; Smeal, Roy M.; Patel, Manisha; Fujinami, Robert S.; White, H. Steve

2017-01-01

Abstract Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler’s murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures. We found a significant increase in both mRNA and protein levels of TNFα and the protein expression ratio of TNF receptors (TNFR1:TNFR2) in the hippocampus, a brain region most likely involved in seizure initiation, after TMEV infection, which suggests that TNFα signaling, predominantly through TNFR1, may contribute to limbic hyperexcitability. An increase in hippocampal cell-surface glutamate receptor expression was also observed during acute seizures. Although pharmacological inhibition of TNFR1-mediated signaling had no effect on acute seizures, several lines of genetically modified animals deficient in either TNFα or TNFRs had robust changes in seizure incidence and severity after TMEV infection. TNFR2–/– mice were highly susceptible to developing acute seizures, suggesting that TNFR2-mediated signaling may provide beneficial effects during the acute seizure period. Taken together, the present results suggest that inflammation in the hippocampus, caused predominantly by TNFα signaling, contributes to hyperexcitability and acute seizures after TMEV infection. Pharmacotherapies designed to suppress TNFR1-mediated or augment TNFR2-mediated effects of TNFα may provide antiseizure and disease-modifying effects after central nervous system infection. PMID:28497109

Searching for the Origin through Central Nervous System: A Review and Thought which Related to Microgravity, Evolution, Big Bang Theory and Universes, Soul and Brainwaves, Greater Limbic System and Seat of the Soul.

PubMed

Idris, Zamzuri

2014-07-01

Cerebrospinal fluid (CSF) serves buoyancy. The buoyancy thought to play crucial role in many aspects of the central nervous system (CNS). Weightlessness is produced mainly by the CSF. This manuscript is purposely made to discuss its significance which thought contributing towards an ideal environment for the CNS to develop and function normally. The idea of microgravity environment for the CNS is supported not only by the weightlessness concept of the brain, but also the noted anatomical position of the CNS. The CNS is positioned in bowing position (at main cephalic flexure) which is nearly similar to an astronaut in a microgravity chamber, fetus in the amniotic fluid at early gestation, and animals and plants in the ocean or on the land. Therefore, this microgravity position can bring us closer to the concept of origin. The hypothesis on 'the origin' based on the microgravity were explored and their similarities were identified including the brainwaves and soul. Subsequently a review on soul was made. Interestingly, an idea from Leonardo da Vinci seems in agreement with the notion of seat of the soul at the greater limbic system which has a distinctive feature of "from God back to God".

Can Decision Making Research Provide a Better Understanding of Chemical and Behavioral Addictions?

PubMed

Engel, Anzhelika; Cáceda, Ricardo

2015-01-01

We reviewed the cognitive and neurobiological commonalities between chemical and behavioral addictions. Poor impulse control, limited executive function and abnormalities in reward processing are seen in both group of entities. Brain imaging shows consistent abnormalities in frontoparietal regions and the limbic system. In drug addiction, exaggerated risk taking behavior and temporal discounting may reflect an imbalance between a hyperactive mesolimbic and hypoactive executive systems. Several cognitive distortions are found in pathological gambling that seems to harness the brain reward system that has evolved to face situations related to skill, not random chance. Abnormalities in risk assessment and impulsivity are found in variety of eating disorders, in particularly related to eating behavior. Corresponding findings in eating disorder patients include abnormalities in the limbic system, i.e. orbitofrontal cortex (OFC), striatum and insula. Similarly, internet addiction disorder is associated with risky decision making and increased choice impulsivity with corresponding discrepant activation in the dorsolateral prefrontal cortex, OFC, anterior cingulate cortex, caudate and insula. Sexual addictions are in turn associated with exaggerated impulsive choice and suggestive evidence of abnormalities in reward processing. In sum, exploration of executive function and decision making abnormalities in chemical and behavioral addictions may increase understanding in their psychopathology and yield valuable targets for therapeutic interventions.

Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia

PubMed Central

Borroto-Escuela, Dasiel O.; Pintsuk, Julia; Schäfer, Thorsten; Friedland, Kristina; Ferraro, Luca; Tanganelli, Sergio; Liu, Fang; Fuxe, Kjell

2016-01-01

The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A–D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor–receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A–D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2–N-methyl-d-aspartate (NMDA) and A2A–D2–metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)–D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of pathological allosteric facilitatory 5-HT2A–D2 interaction increasing D2 protomer signaling. Neurotensin (NTS1)–D2 heterocomplexes also exist in the ventral and dorsal striatum, and likely also in midbrain DA nerve cells as NTS1-D2 autoreceptor complexes where neurotensin produces antipsychotic and propsychotic actions, respectively. PMID:27141290

Limbic and prefrontal responses to facial emotion expressions in depersonalization.

PubMed

Lemche, Erwin; Surguladze, Simon A; Giampietro, Vincent P; Anilkumar, Ananthapadmanabha; Brammer, Michael J; Sierra, Mauricio; Chitnis, Xavier; Williams, Steven C R; Gasston, David; Joraschky, Peter; David, Anthony S; Phillips, Mary L

2007-03-26

Depersonalization disorder, characterized by emotional detachment, has been associated with increased prefrontal cortical and decreased autonomic activity to emotional stimuli. Event-related fMRI with simultaneous measurements of skin conductance levels occurred in nine depersonalization disorder patients and 12 normal controls to neutral, mild and intense happy and sad facial expressions. Patients, but not controls, showed decreases in subcortical limbic activity to increasingly intense happy and sad facial expressions, respectively. For both happy and sad expressions, negative correlations between skin conductance measures in bilateral dorsal prefrontal cortices occurred only in depersonalization disorder patients. Abnormal decreases in limbic activity to increasingly intense emotional expressions, and increases in dorsal prefrontal cortical activity to emotionally arousing stimuli may underlie the emotional detachment of depersonalization disorder.

Hippocampus and Amygdala Morphology in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Plessen, Kerstin J.; Bansal, Ravi; Zhu, Hongtu; Whiteman, Ronald; Amat, Jose; Quackenbush, Georgette A.; Martin, Laura; Durkin, Kathleen; Blair, Clancy; Royal, Jason; Hugdahl, Kenneth; Peterson, Bradley S.

2008-01-01

Context Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. Objective To study the morphology of the hippocampus and amygdala in children with ADHD. Design A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. Settings University research institute. Patients One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63 healthy controls. Main Outcome Measures Volumes and measures of surface morphology for the hippocampus and amygdala. Results The hippocampus was larger bilaterally in the ADHD group than in the control group (t=3.35; P<.002). Detailed surface analyses of the hippocampus further localized these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. Conclusions The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing (eg, delay aversion), and stimulus seeking associated with ADHD. Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition. Our findings suggest involvement of the limbic system in the pathophysiology of ADHD. PMID:16818869

Stress and the developing adolescent brain.

PubMed

Eiland, L; Romeo, R D

2013-09-26

Adolescence is a time of continued brain maturation, particularly in limbic and cortical regions, which undoubtedly plays a role in the physiological and emotional changes coincident with adolescence. An emerging line of research has indicated that stressors experienced during this crucial developmental stage may affect the trajectory of this neural maturation and contribute to the increase in psychological morbidities, such as anxiety and depression, often observed during adolescence. In this review, we discuss the short- and long-term effects of periadolescent stress exposure on the structure and function of the brain. More specifically, we examine how stress at prepubertal and early adolescent stages of development affects the morphological plasticity of limbic and cortical brain regions, as well as the enduring effects of adolescent stress exposure on these brain regions in adulthood. We suggest that, due to a number of converging factors during this period of maturation, the adolescent brain may be particularly sensitive to stress-induced neurobehavioral dysfunctions with important consequences on an individual's immediate and long-term health and well-being. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Brain Metabolism during Hallucination-Like Auditory Stimulation in Schizophrenia

PubMed Central

Horga, Guillermo; Fernández-Egea, Emilio; Mané, Anna; Font, Mireia; Schatz, Kelly C.; Falcon, Carles; Lomeña, Francisco; Bernardo, Miguel; Parellada, Eduard

2014-01-01

Auditory verbal hallucinations (AVH) in schizophrenia are typically characterized by rich emotional content. Despite the prominent role of emotion in regulating normal perception, the neural interface between emotion-processing regions such as the amygdala and auditory regions involved in perception remains relatively unexplored in AVH. Here, we studied brain metabolism using FDG-PET in 9 remitted patients with schizophrenia that previously reported severe AVH during an acute psychotic episode and 8 matched healthy controls. Participants were scanned twice: (1) at rest and (2) during the perception of aversive auditory stimuli mimicking the content of AVH. Compared to controls, remitted patients showed an exaggerated response to the AVH-like stimuli in limbic and paralimbic regions, including the left amygdala. Furthermore, patients displayed abnormally strong connections between the amygdala and auditory regions of the cortex and thalamus, along with abnormally weak connections between the amygdala and medial prefrontal cortex. These results suggest that abnormal modulation of the auditory cortex by limbic-thalamic structures might be involved in the pathophysiology of AVH and may potentially account for the emotional features that characterize hallucinatory percepts in schizophrenia. PMID:24416328

The surface of the eye – a superficial entity with deep repercussions

PubMed Central

Potop, Vasile; Dumitrache, Marieta; Ciocalteu, Alina

2009-01-01

The surface of the eye is an anatomical and functional entity with a relatively recent delimitation but with significant therapeutic and diagnostic consequences. The pathology of the conjunctive and cornea must be approached by looking at the interrelations between the two tissues that are so different anatomically and functionally but in the same time form a unit in structuring the eye’s surface. There are two major categories of relations between the two tissues: one of them is mediated by lachrymal secretion, a process whose complexity is not yet fully understood, and the other is germinal, referring to the stem cells located at the limbus which become epithelial cornea cells that can fixate lachrymal fluid. Imbalances in the quantity and quality of lachrymal secretion can be compensated, up to a certain point, by artificial products, but in severe cases only specially prepared autologous serum can compensate the deficit. The limbic deficits that affect stem cells require complex therapeutic procedures like limbic cell transplant, using an amniotic membrane or autologous serum. PMID:20108493

[Why do we call the brain 'brain'?

PubMed

Garcia-Molina, A; Ensenat, A

2017-01-16

Every day millions of professionals use a countless number of technical words to refer to the different structures inside the skull. But few of them would know how to explain their origin. In this study we take an in-depth look into the etymological origins of some of these neuroanatomical terms. The study takes an etymological tour of the central nervous system. It is in no way meant to be an exhaustive, detailed review of the terms currently in use, but instead a means to familiarise the reader with the linguistic past of words like brain, hippocampus, thalamus, claustrum, fornix, corpus callosum or limbic system. All of them come from either Greek or Latin, which were used for centuries as the lingua francas of science. The study also analyses the evolution of the word meninges, originally of Greco-Latin origin, although its current usages derive from Arabic. The neuroanatomical terms that are in use today do not come from words that associate a particular brain structure with its function, but instead from words that reflect the formal or conceptual similarity between a structure and a familiar or everyday entity (for example, an object or a part of the human body). In other cases, these words indicate the spatial location of the neuroanatomical structure with respect to a third, or they may be terms derived from characters in Greco-Latin mythology.

Lingual and fusiform gyri in visual processing: a clinico-pathologic study of superior altitudinal hemianopia.

PubMed Central

Bogousslavsky, J; Miklossy, J; Deruaz, J P; Assal, G; Regli, F

1987-01-01

A macular-sparing superior altitudinal hemianopia with no visuo-psychic disturbance, except impaired visual learning, was associated with bilateral ischaemic necrosis of the lingual gyrus and only partial involvement of the fusiform gyrus on the left side. It is suggested that bilateral destruction of the lingual gyrus alone is not sufficient to affect complex visual processing. The fusiform gyrus probably has a critical role in colour integration, visuo-spatial processing, facial recognition and corresponding visual imagery. Involvement of the occipitotemporal projection system deep to the lingual gyri probably explained visual memory dysfunction, by a visuo-limbic disconnection. Impaired verbal memory may have been due to posterior involvement of the parahippocampal gyrus and underlying white matter, which may have disconnected the intact speech areas from the left medial temporal structures. Images PMID:3585386

Autistic disorder: a review for the pediatric dentist.

PubMed

Klein, U; Nowak, A J

1998-01-01

Dental publications on autism have been sparse since the first comprehensive article geared for the dental profession. New findings on the etiology of autistic disorder (AD) have been discovered, suggesting that it is an organic disorder characterized by abnormalities in the brain, especially the cerebellum and limbic system. This article summarizes the latest medical findings on the etiology, diagnosis, and treatment approaches of AD, and reviews the dental literature since 1969. The main dental topics reviewed are: oral health status and dental needs of patients with AD, characteristics of patients with AD, and self-injurious behavior (SIB) in the context of AD. Clinical behavior-management issues such as pharmacological and communicative techniques and physical restraint and desensitization are described. The affect of the dental office's environment and appointment structure on a patient with AD are presented.

Ontogenesis of the angiotensin II (ANGII) receptor system in the duck brain.

PubMed

Müller, A R; Gerstberger, R

1994-03-18

The ontogenetic development of the central nervous angiotensin II (ANGII) receptor system in the duck was studied at embryonic days E20 and E27 and at postnatal days P3 and P14 by computerized semiquantitative autoradiography employing the receptor antagonist 125I[1Sar,8Ile]ANGII as radioligand. For circumventricular structures involved in the sensing of brain-intrinsic (AV3V region) or blood-borne (subfornical organ, SFO) ANGII, binding sites for 125I[1Sar,8Ile]ANGII were first detectable at E27, with a steady rise in binding density up to P14. The choroid plexus of the lateral (PCVL) and third (PCVIII) cerebral ventricles responsible for cerebrospinal fluid (CSF) production were endowed with maximal ANGII receptor densities at E20 with subsequent reduction to constant medium (PCVIII) or low (PCVL) values. Besides the choroid plexus, the magnocellular paraventricular nucleus (PVN) was the only structure presenting ANGII specific binding sites at E20, although at low density. As for the SFO and AV3V region, labelling of ANGII binding sites in the PVN increased continuously during development to high values at P14. Nuclear components of the limbic system (archistriatum, amygdala and habenular complex) did not reveal specific labelling by the radioligand at E20 with constant, moderate binding densities evaluated for E27, P3 and P14. In the duck brain, functionally related structures exhibited a homogeneous ontogenetic development of their ANGII receptor system.

The Neuropathology of Autism

PubMed Central

Blatt, Gene J.

2012-01-01

Autism is a behaviorally defined neurodevelopmental disorder that affects over 1% of new births in the United States and about 2% of boys. The etiologies are unknown and they are genetically complex. There may be epigenetic effects, environmental influences, and other factors that contribute to the mechanisms and affected neural pathway(s). The underlying neuropathology of the disorder has been evolving in the literature to include specific brain areas in the cerebellum, limbic system, and cortex. Part(s) of structures appear to be affected most rather than the entire structure, for example, select nuclei of the amygdala, the fusiform face area, and so forth. Altered cortical organization characterized by more frequent and narrower minicolumns and early overgrowth of the frontal portion of the brain, affects connectivity. Abnormalities include cytoarchitectonic laminar differences, excess white matter neurons, decreased numbers of GABAergic cerebellar Purkinje cells, and other events that can be traced developmentally and cause anomalies in circuitry. Problems with neurotransmission are evident by recent receptor and binding site studies especially in the inhibitory GABA system likely contributing to an imbalance of excitatory/inhibitory transmission. As postmortem findings are related to core behavior symptoms, and technology improves, researchers are gaining a much better perspective of contributing factors to the disorder. PMID:24278731

Neurobiological factors in aggressive behavior.

PubMed

Garza-Treviño, E S

1994-07-01

The author's aim was to review literature in the neurosciences and psychiatric clinical research reports about biological factors in aggression and the pathophysiological mechanisms that accompany aggression in neuropsychiatric syndromes. Studies were located through computer searches of relevant experimental reports and review articles mainly from the last 25 years. Several studies using neuroimaging and neurophysiological and neuropathological research techniques have identified lesions in the limbic structures, temporal lobes, and frontal lobes of the brain in abnormally aggressive individuals. Several reports have associated deficiency or dysregulation of serotonin with homicidal, suicidal, and impulsive behavior. However, few studies have focused on polypeptides or second messenger systems, although abnormalities in these systems have been reported in patients with neuropsychiatric syndromes who have shown aggressive behavior. Even fewer studies focus on the correlation of brain structures and metabolic markers. The understanding of aggressive behavior in psychiatric patients is fragmented. Some explanations are speculative and extrapolated to clinical psychiatric syndromes from experimental data on the neurophysiology of cats, rats, and other mammals. Identification of biochemical markers that can be used in predicting patients' response to pharmacological interventions may be the next step in developing more rational treatment of violent patients.

Fronto-limbic effective connectivity as possible predictor of antidepressant response to SSRI administration.

PubMed

Vai, Benedetta; Bulgarelli, Chiara; Godlewska, Beata R; Cowen, Philip J; Benedetti, Francesco; Harmer, Catherine J

2016-12-01

The timely selection of the optimal treatment for depressed patients is critical to improve remission rates. The detection of pre-treatment variables able to predict differential treatment response may provide novel approaches for treatment selection. Selective serotonin reuptake inhibitors (SSRIs) modulate the fronto-limbic functional response and connectivity, an effect preceding the overt clinical antidepressant effects. Here we investigated whether the cortico-limbic connectivity associated with emotional bias measured before SSRI administration predicts the efficacy of antidepressant treatment in MDD patients. fMRI and Dynamic Causal Modeling (DCM) were combined to study if effective connectivity might differentiate healthy controls (HC) and patients affected by major depression who later responded (RMDD, n=21), or failed to respond (nRMDD, n=12), to 6 weeks of escitalopram administration. Sixteen DCMs exploring connectivity between anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), Amygdala (Amy), and fusiform gyrus (FG) were constructed. Analyses revealed that nRMDD had reduced endogenous connectivity from Amy to VLPFC and to ACC, with an increased connectivity and modulation of the ACC to Amy connectivity when processing of fearful emotional stimuli compared to HC. RMDD and HC did not significantly differ among themselves. Pre-treatment effective connectivity in fronto-limbic circuitry could be an important factor affecting antidepressant response, and highlight the mechanisms which may be involved in recovery from depression. These results suggest that fronto-limbic connectivity might provide a neural biomarker to predict the clinical outcome to SSRIs administration in major depression. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Synchronous inhibitory potentials precede seizure-like events in acute models of focal limbic seizures.

PubMed

Uva, Laura; Breschi, Gian Luca; Gnatkovsky, Vadym; Taverna, Stefano; de Curtis, Marco

2015-02-18

Interictal spikes in models of focal seizures and epilepsies are sustained by the synchronous activation of glutamatergic and GABAergic networks. The nature of population spikes associated with seizure initiation (pre-ictal spikes; PSs) is still undetermined. We analyzed the networks involved in the generation of both interictal and PSs in acute models of limbic cortex ictogenesis induced by pharmacological manipulations. Simultaneous extracellular and intracellular recordings from both principal cells and interneurons were performed in the medial entorhinal cortex of the in vitro isolated guinea pig brain during focal interictal and ictal discharges induced in the limbic network by intracortical and brief arterial infusions of either bicuculline methiodide (BMI) or 4-aminopyridine (4AP). Local application of BMI in the entorhinal cortex did not induce seizure-like events (SLEs), but did generate periodic interictal spikes sensitive to the glutamatergic non-NMDA receptor antagonist DNQX. Unlike local applications, arterial perfusion of either BMI or 4AP induced focal limbic SLEs. PSs just ahead of SLE were associated with hyperpolarizing potentials coupled with a complete blockade of firing in principal cells and burst discharges in putative interneurons. Interictal population spikes recorded from principal neurons between two SLEs correlated with a depolarizing potential. We demonstrate in two models of acute limbic SLE that PS events are different from interictal spikes and are sustained by synchronous activation of inhibitory networks. Our findings support a prominent role of synchronous network inhibition in the initiation of a focal seizure. Copyright © 2015 the authors 0270-6474/15/353048-08$15.00/0.

Neurotrophic Substances and Behavioral Recovery from Brain Damage.

DTIC Science & Technology

1983-07-01

intracerebral administration of this substance can increase choline acetyltransferase, an enzyme necessary for the production of neurotransmitter. This...from limbic system 1 Hefti, F., Dravid, A. and Hartikka, J. Chronic intraventricular injections of nerve growth factor elevate hippocampal choline ...testing, the animals were killed with an overdose of anesthetic (Nembutal) and perfused intracardially with saline-formalin solution. Their brains

The tempted brain eats: Pleasure and desire circuits in obesity and eating disorders

PubMed Central

Berridge, Kent C.; Ho, Chao-Yi; Richard, Jocelyn M.; DiFeliceantonio, Alexandra G.

2010-01-01

What we eat, when and how much, all are influenced by brain reward mechanisms that generate ‘liking’ and ‘wanting’ for foods. As a corollary, dysfunction in reward circuits might contribute to the recent rise of obesity and eating disorders. Here we assess brain mechanisms known to generate ‘liking’ and ‘wanting’ for foods, and evaluate their interaction with regulatory mechanisms of hunger and satiety, relevant to clinical issues. ‘Liking’ mechanisms include hedonic circuits that connect together cubic-millimeter hotspots in forebrain limbic structures such as nucleus accumbens and ventral pallidum (where opioid/endocannabinoid/orexin signals can amplify sensory pleasure). ‘Wanting’ mechanisms include larger opioid networks in nucleus accumbens, striatum, and amygdala that extend beyond the hedonic hotspots, as well as mesolimbic dopamine systems, and corticolimbic glutamate signals that interact with those systems. We focus on ways in which these brain reward circuits might participate in obesity or in eating disorders. PMID:20388498

From receptor balance to rational glucocorticoid therapy.

PubMed

de Kloet, E Ron

2014-08-01

Corticosteroids secreted as end product of the hypothalamic-pituitary-adrenal axis act like a double-edged sword in the brain. The hormones coordinate appraisal processes and decision making during the initial phase of a stressful experience and promote subsequently cognitive performance underlying the management of stress adaptation. This action exerted by the steroids on the initiation and termination of the stress response is mediated by 2 related receptor systems: mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). The receptor types are unevenly distributed but colocalized in abundance in neurons of the limbic brain to enable these complementary hormone actions. This contribution starts from a historical perspective with the observation that phasic occupancy of GR during ultradian rhythmicity is needed to maintain responsiveness to corticosteroids. Then, during stress, initially MR activation enhances excitability of limbic networks that are engaged in appraisal and emotion regulation. Next, the rising hormone concentration occupies GR, resulting in reallocation of energy to limbic-cortical circuits with a role in behavioral adaptation and memory storage. Upon MR:GR imbalance, dysregulation of the hypothalamic-pituitary-adrenal axis occurs, which can enhance an individual's vulnerability. Imbalance is characteristic for chronic stress experience and depression but also occurs during exposure to synthetic glucocorticoids. Hence, glucocorticoid psychopathology may develop in susceptible individuals because of suppression of ultradian/circadian rhythmicity and depletion of endogenous corticosterone from brain MR. This knowledge generated from testing the balance hypothesis can be translated to a rational glucocorticoid therapy.

Virtual Reality Therapy for the Treatment of Alcohol Dependence: A Preliminary Investigation With Positron Emission Tomography/Computerized Tomography.

PubMed

Son, Ji Hyun; Lee, Sang Hoon; Seok, Ju Won; Kee, Baik Seok; Lee, Hyun Woong; Kim, Hyung Joon; Lee, Tae Kyung; Han, Doug Hyun

2015-07-01

Virtual reality therapy (VRT) uses multimodal stimulation that includes visual, auditory, olfactory, and gustatory stimuli. The aim of this study was to assess the effectiveness of VRT in treating subjects with alcohol dependence (AD) by evaluating changes in brain metabolism. The VRT protocol consisted of three steps: relaxation, presentation of a high-risk situation, and presentation of an aversive situation. Twelve alcohol-dependent subjects underwent 10 sessions of VRT. The alcohol-dependent subjects were assessed with 18F-fluorodeoxyglucose positron emission tomography images before and after VRT, whereas the control group underwent imaging according to the same protocol only at baseline. Compared with the healthy control group, AD subjects showed higher metabolism in the right lentiform nucleus and right temporal lobe (BA20) at baseline (P(FDR < .05) = .026). In addition, the metabolism in the left anterior cingulate was lower in subjects with AD (P(uncorr) = .001). After VRT, alcohol-dependent subjects showed decreased brain metabolism in the right lentiform nucleus (P(FDR < .05) = .026) and right temporal lobe (BA38, P(FDR < .05) = .032) relative to that at baseline. Our results suggest a neurobiological imbalance, notably, a high sensitivity to stimuli, in the limbic system in subjects with AD. Furthermore, we determined that metabolism decreased in the basal ganglia after VRT, which may explain the limbic-regulated responses of reward and regulation. Therefore, we tentatively recommend VRT to treat AD through its regulating effect on limbic circuits.

Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaminski, Rafal M.; Blaszczak, Piotr; Dekundy, Andrzej

2007-03-15

Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithiummore » pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality.« less

Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies

PubMed Central

Kober, Hedy; Barrett, Lisa Feldman; Joseph, Josh; Bliss-Moreau, Eliza; Lindquist, Kristen; Wager, Tor D.

2009-01-01

We performed an updated quantitative meta-analysis of 162 neuroimaging studies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the cognitive generation of emotional states. PMID:18579414

Changes in brain connectivity related to the treatment of depression measured through fMRI: a systematic review

PubMed Central

Gudayol-Ferré, Esteve; Peró-Cebollero, Maribel; González-Garrido, Andrés A.; Guàrdia-Olmos, Joan

2015-01-01

Depression is a mental illness that presents alterations in brain connectivity in the Default Mode Network (DMN), the Affective Network (AN) and other cortical-limbic networks, and the Cognitive Control Network (CCN), among others. In recent years the interest in the possible effect of the different antidepressant treatments on functional connectivity has increased substantially. The goal of this paper is to conduct a systematic review of the studies on the relationship between the treatment of depression and brain connectivity. Nineteen studies were found in a systematic review on this topic. In all of them, there was improvement of the clinical symptoms after antidepressant treatment. In 18 out of the 19 studies, clinical improvement was associated to changes in brain connectivity. It seems that both DMN and the connectivity between cortical and limbic structures consistently changes after antidepressant treatment. However, the current evidence does not allow us to assure that the treatment of depression leads to changes in the CCN. In this regard, some papers report a positive correlation between changes in brain connectivity and improvement of depressive symptomatology, particularly when they measure cortical-limbic connectivity, whereas the changes in DMN do not significantly correlate with clinical improvement. Finally, some papers suggest that changes in connectivity after antidepressant treatment might be partly related to the mechanisms of action of the treatment administered. This effect has been observed in two studies with stimulation treatment (one with rTMS and one with ECT), and in two papers that administered three different pharmacological treatments. Our review allows us to make a series of recommendations that might guide future researchers exploring the effect of anti-depression treatments on brain connectivity. PMID:26578927

Early life stress and trauma and enhanced limbic activation to emotionally valenced faces in depressed and healthy children.

PubMed

Suzuki, Hideo; Luby, Joan L; Botteron, Kelly N; Dietrich, Rachel; McAvoy, Mark P; Barch, Deanna M

2014-07-01

Previous studies have examined the relationships between structural brain characteristics and early life stress in adults. However, there is limited evidence for functional brain variation associated with early life stress in children. We hypothesized that early life stress and trauma would be associated with increased functional brain activation response to negative emotional faces in children with and without a history of depression. Psychiatric diagnosis and life events in children (starting at age 3-5 years) were assessed in a longitudinal study. A follow-up magnetic resonance imaging (MRI) study acquired data (N = 115 at ages 7-12, 51% girls) on functional brain response to fearful, sad, and happy faces relative to neutral faces. We used a region-of-interest mask within cortico-limbic areas and conducted regression analyses and repeated-measures analysis of covariance. Greater activation responses to fearful, sad, and happy faces in the amygdala and its neighboring regions were found in children with greater life stress. Moreover, an association between life stress and left hippocampal and globus pallidus activity depended on children's diagnostic status. Finally, all children with greater life trauma showed greater bilateral amygdala and cingulate activity specific to sad faces but not the other emotional faces, although right amygdala activity was moderated by psychiatric status. These findings suggest that limbic hyperactivity may be a biomarker of early life stress and trauma in children and may have implications in the risk trajectory for depression and other stress-related disorders. However, this pattern varied based on emotion type and history of psychopathology. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Grey matter alterations in migraine: A systematic review and meta-analysis.

PubMed

Jia, Zhihua; Yu, Shengyuan

2017-01-01

To summarize and meta-analyze studies on changes in grey matter (GM) in patients with migraine. We aimed to determine whether there are concordant structural changes in the foci, whether structural changes are concordant with functional changes, and provide further understanding of the anatomy and biology of migraine. We searched PubMed and Embase for relevant articles published between January 1985 and November 2015, and examined the references within relevant primary articles. Following exclusion of unsuitable studies, meta-analysis were performed using activation likelihood estimation (ALE). Eight clinical studies were analyzed for structural changes, containing a total of 390 subjects (191 patients and 199 controls). Five functional studies were enrolled, containing 93 patients and 96 controls. ALE showed that the migraineurs had concordant decreases in the GM volume (GMV) in the bilateral inferior frontal gyri, the right precentral gyrus, the left middle frontal gyrus and the left cingulate gyrus. GMV decreases in right claustrum, left cingulated gyrus, right anterior cingulate, amygdala and left parahippocampal gyrus are related to estimated frequency of headache attack . Activation was found in the somatosensory, cingulate, limbic lobe, basal ganglia and midbrain in migraine patients. GM changes in migraineurs may indicate the mechanism of pain processing and associated symptoms. Changes in the frontal gyrus may predispose a person to pain conditions. The limbic regions may be accumulated damage due to the repetitive occurrence of pain-related processes. Increased activation in precentral gyrus and cingulate opposed to GMV decrease might suggest increased effort duo to disorganization of these areas and/or the use of compensatory strategies involving pain processing in migraine. Knowledge of these structural and functional changes may be useful for monitoring disease progression as well as for therapeutic interventions.

Clinical analysis of anti-Ma2-associated encephalitis.

PubMed

Dalmau, Josep; Graus, Francesc; Villarejo, Alberto; Posner, Jerome B; Blumenthal, Deborah; Thiessen, Brian; Saiz, Albert; Meneses, Patricio; Rosenfeld, Myrna R

2004-08-01

Increasing experience indicates that anti-Ma2-associated encephalitis differs from classical paraneoplastic limbic or brainstem encephalitis, and therefore may be unrecognized. To facilitate its diagnosis we report a comprehensive clinical analysis of 38 patients with anti-Ma2 encephalitis. Thirty-four (89%) patients presented with isolated or combined limbic, diencephalic or brainstem dysfunction, and four with other syndromes. Considering the clinical and MRI follow-up, 95% of the patients developed limbic, diencephalic or brainstem encephalopathy. Only 26% had classical limbic encephalitis. Excessive daytime sleepiness affected 32% of the patients, sometimes with narcolepsy-cataplexy and low CSF hypocretin. Additional hormonal or MRI abnormalities indicated diencephalic-hypothalamic involvement in 34% of the patients. Eye movement abnormalities were prominent in 92% of the patients with brainstem dysfunction, but those with additional limbic or diencephalic deficits were most affected; 60% of these patients had vertical gaze paresis that sometimes evolved to total external ophthalmoplegia. Three patients developed atypical parkinsonism, and two a severe hypokinetic syndrome with a tendency to eye closure and dramatic reduction of verbal output. Neurological symptoms preceded the tumour diagnosis in 62% of the patients. Brain MRI abnormalities were present in 74% of all patients and 89% of those with limbic or diencephalic dysfunction. Among the 34 patients with cancer, 53% had testicular germ-cell tumours. Two patients without evidence of cancer had testicular microcalcification and one cryptorchidism, risk factors for testicular germ-cell tumours. After neurological syndrome development, 17 of 33 patients received oncological treatment (nine also immunotherapy), 10 immunotherapy alone, and six no treatment. Overall, 33% of the patients had neurological improvement, three with complete recovery; 21% had long-term stabilization, and 46% deteriorated. Features significantly associated with improvement or stabilization included, male gender, age <45 years, testicular tumour with complete response to treatment, absence of anti-Ma1 antibodies and limited CNS involvement. Immunosuppression was not found to be associated with improvement but was clearly effective in some patients. Fifteen patients (10 women, five men) had additional antibodies to Ma1. These patients were more likely to have tumours other than testicular cancer and to develop ataxia, and had a worse prognosis than patients with only anti-Ma2 antibodies (two women, 21 men); 67% of deceased patients had anti-Ma1 antibodies. Anti-Ma2 encephalitis (with or without anti-Ma1 antibodies) should be suspected in patients with limbic, diencephalic or brainstem dysfunction, MRI abnormalities in these regions, and inflammatory changes in the CSF. In young male patients, the primary tumour is usually in the testis, in other patients the leading neoplasm is lung cancer.

Failure to Recover from Proactive Semantic Interference and Abnormal Limbic Connectivity in Asymptomatic, Middle-Aged Offspring of Patients with Late-Onset Alzheimer's Disease.

PubMed

Sánchez, Stella M; Abulafia, Carolina; Duarte-Abritta, Barbara; de Guevara, M Soledad Ladrón; Castro, Mariana N; Drucaroff, Lucas; Sevlever, Gustavo; Nemeroff, Charles B; Vigo, Daniel E; Loewenstein, David A; Villarreal, Mirta F; Guinjoan, Salvador M

2017-01-01

We have obtained previous evidence of limbic dysfunction in middle-aged, asymptomatic offspring of late-onset Alzheimer's disease (LOAD) patients, and failure to recover from proactive semantic interference has been shown to be a sensitive cognitive test in other groups at risk for LOAD. To assess the effects of specific proactive semantic interference deficits as they relate to functional magnetic resonance imaging (fMRI) neocortical and limbic functional connectivity in middle aged offspring of individuals with LOAD (O-LOAD) and age-equivalent controls. We examined 21 O-LOAD and 20 controls without family history of neurodegenerative disorders (CS) on traditional measures of cognitive functioning and the LASSI-L, a novel semantic interference test uniquely sensitive to the failure to recover from proactive interference (frPSI). Cognitive tests then were correlated to fMRI connectivity of seeds located in entorhinal cortex and anterodorsal thalamic nuclei among O-LOAD and CS participants. Relative to CS, O-LOAD participants evidenced lower connectivity between entorhinal cortex and orbitofrontal, anterior cingulate, and anterior temporal cortex. In the offspring of LOAD patients, LASSI-L measures of frPSI were inversely associated with connectivity between anterodorsal thalamus and contralateral posterior cingulate. Intrusions on the task related to frPSI were inversely correlated with a widespread connectivity network involving hippocampal, insular, posterior cingulate, and dorsolateral prefrontal cortices, along with precunei and anterior thalamus in this group. Different patterns of connectivity associated with frPSI were observed among controls. The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations.

SPECT and PET analysis of subthalamic stimulation in Parkinson's disease: analysis using a manual segmentation.

PubMed

Haegelen, Claire; García-Lorenzo, Daniel; Le Jeune, Florence; Péron, Julie; Gibaud, Bernard; Riffaud, Laurent; Brassier, Gilles; Barillot, Christian; Vérin, Marc; Morandi, Xavier

2010-03-01

The subthalamic nucleus (STN) has become an effective target of deep-brain stimulation (DBS) in severely disabled patients with advanced Parkinson's disease (PD). Clinical studies have reported DBS-induced adverse effects on cognitive functions, mood, emotion and behavior. STN DBS seems to interfere with the limbic functions of the basal ganglia, but the limbic effects of STN DBS are controversial. We measured prospectively resting regional cerebral metabolism (rCMb) with 18-fluorodeoxyglucose and PET, and resting regional cerebral blood flow (rCBF) with HMPAO and SPECT in six patients with Parkinson's disease. We compared PET and SPECT 1 month before and 3 months after STN DBS. On cerebral MRI, 13 regions of interest (ROI) were manually delineated slice by slice in frontal and limbic lobes. We obtained mean rCBF and rCMb values for each ROI and the whole brain. We normalized rCBF and rCMB values to ones for the whole brain volume, which we compared before and following STN DBS. No significant difference emerged in the SPECT analysis. PET analysis revealed a significant decrease in rCMb following STN DBS in the superior frontal gyri and left and right dorsolateral prefrontal cortex (p < 0.05). A non-significant decrease in rCMb in the left anterior cingulate gyrus appeared following STN DBS (p = 0.075). Our prospective SPECT and PET study revealed significantly decreased glucose metabolism of the two superior frontal gyri without any attendant perfusion changes following STN DBS. These results suggest that STN DBS may change medial prefrontal function and therefore the integration of limbic information, either by disrupting emotional processes within the STN, or by hampering the normal function of a limbic circuit.

Stimulation of subgenual cingulate area decreases limbic top-down effect on ventral visual stream: A DBS-EEG pilot study.

PubMed

Kibleur, Astrid; Polosan, Mircea; Favre, Pauline; Rudrauf, David; Bougerol, Thierry; Chabardès, Stéphan; David, Olivier

2017-02-01

Deep brain stimulation (DBS) of the subgenual cingulate gyrus (area CG25) is beneficial in treatment resistant depression. Though the mechanisms of action of Cg25 DBS remain largely unknown, it is commonly believed that Cg25 DBS modulates limbic activity of large networks to achieve thymic regulation of patients. To investigate how emotional attention is influenced by Cg25 DBS, we assessed behavioral and electroencephalographic (EEG) responses to an emotional Stroop task in 5 patients during ON and OFF stimulation conditions. Using EEG source localization, we found that the main effect of DBS was a reduction of neuronal responses in limbic regions (temporal pole, medial prefrontal and posterior cingulate cortices) and in ventral visual areas involved in face processing. In the dynamic causal modeling (DCM) approach, the changes of the evoked response amplitudes are assumed to be due to changes of long range connectivity induced by Cg25 DBS. Here, using a simplified neural mass model that did not take explicitly into account the cytoarchitecture of the considered brain regions, we showed that the remote action of Cg25 DBS could be explained by a reduced top-down effective connectivity of the amygdalo-temporo-polar complex. Overall, our results thus indicate that Cg25 DBS during the emotional Stroop task causes a decrease of top-down limbic influence on the ventral visual stream itself, rather than a modulation of prefrontal cognitive processes only. Tuning down limbic excitability in relation to sensory processing might be one of the biological mechanisms through which Cg25 DBS produces positive clinical outcome in the treatment of resistant depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Searching for the Origin through Central Nervous System: A Review and Thought which Related to Microgravity, Evolution, Big Bang Theory and Universes, Soul and Brainwaves, Greater Limbic System and Seat of the Soul

PubMed Central

IDRIS, Zamzuri

2014-01-01

Cerebrospinal fluid (CSF) serves buoyancy. The buoyancy thought to play crucial role in many aspects of the central nervous system (CNS). Weightlessness is produced mainly by the CSF. This manuscript is purposely made to discuss its significance which thought contributing towards an ideal environment for the CNS to develop and function normally. The idea of microgravity environment for the CNS is supported not only by the weightlessness concept of the brain, but also the noted anatomical position of the CNS. The CNS is positioned in bowing position (at main cephalic flexure) which is nearly similar to an astronaut in a microgravity chamber, fetus in the amniotic fluid at early gestation, and animals and plants in the ocean or on the land. Therefore, this microgravity position can bring us closer to the concept of origin. The hypothesis on ‘the origin’ based on the microgravity were explored and their similarities were identified including the brainwaves and soul. Subsequently a review on soul was made. Interestingly, an idea from Leonardo da Vinci seems in agreement with the notion of seat of the soul at the greater limbic system which has a distinctive feature of “from God back to God”. PMID:25977615

Effects of p75NTR deficiency on cholinergic innervation of the amygdala and anxiety-like behavior.

PubMed

Busch, Ruben; Baldus, Marian; Vogt, Miriam A; Berger, Stefan M; Bartsch, Dusan; Gass, Peter; von Bohlen Und Halbach, Oliver

2017-05-01

The p75 neurotrophin receptor (p75NTR) is a low-affinity receptor that is capable of binding neurotrophins. Two different p75NTR knockout mouse lines are available either with a deletion in Exon III (p75NTR E x III -/- ) or in Exon IV (p75NTR E x IV -/- ). In p75NTR E x III knockout mice, only the full-length p75NTR is deleted, whereas in p75NTR E x IV knockout mice, the full-length as well as the truncated isoform of the receptor is deleted. Deletion of p75NTR has been shown to affect, among others, the septohippocampal cholinergic innervation pattern and neuronal plasticity within the hippocampus. We hypothesize that deletion of p75NTR also alters the morphology and physiology of a further key structure of the limbic system, the amygdala. Our results indicate that deletion of p75NTR also increases cholinergic innervation in the basolateral amygdala in adult as well as aged p75NTR E x III -/- and p75NTR E x IV -/- mice. The p75NTR E x IV -/- mice did not display altered long-term potentiation (LTP) in the basolateral amygdala as compared to age-matched control littermates. However, p75NTR E x III -/- mice display stronger LTP in the basolateral amygdala compared to age-matched controls. Bath-application of K252a (a trk antagonist) did not inhibit the induction of LTP in the basolateral amygdala, but reduced the level of LTP in p75NTR E x III -/- mice to levels seen in respective controls. Moreover, p75NTR E x III -/- mice display altered behavior in the dark/light box. Thus, deletion of p75NTR in mice leads to physiological and morphological changes in the amygdala and altered behavior that is linked to the limbic system. © 2017 International Society for Neurochemistry.

Ectodomain shedding of Limbic System-Associated Membrane Protein (LSAMP) by ADAM Metallopeptidases promotes neurite outgrowth in DRG neurons.

PubMed

Sanz, Ricardo L; Ferraro, Gino B; Girouard, Marie-Pier; Fournier, Alyson E

2017-08-11

IgLONs are members of the immunoglobulin superfamily of cell adhesion proteins implicated in the process of neuronal outgrowth, cell adhesion and subdomain target recognition. IgLONs form homophilic and heterophilic complexes on the cell surface that repress or promote growth depending on the neuronal population, the developmental stage and surface repertoire of IgLON family members. In the present study, we identified a metalloproteinase-dependent mechanism necessary to promote growth in embryonic dorsal root ganglion cells (DRGs). Treatment of embryonic DRG neurons with pan-metalloproteinase inhibitors, tissue inhibitor of metalloproteinase-3, or an inhibitor of ADAM Metallopeptidase Domain 10 (ADAM10) reduces outgrowth from DRG neurons indicating that metalloproteinase activity is important for outgrowth. The IgLON family members Neurotrimin (NTM) and Limbic System-Associated Membrane Protein (LSAMP) were identified as ADAM10 substrates that are shed from the cell surface of DRG neurons. Overexpression of LSAMP and NTM suppresses outgrowth from DRG neurons. Furthermore, LSAMP loss of function decreases the outgrowth sensitivity to an ADAM10 inhibitor. Together our findings support a role for ADAM-dependent shedding of cell surface LSAMP in promoting outgrowth from DRG neurons.

EEG-confirmed epileptic activity in a cat with VGKC-complex/LGI1 antibody-associated limbic encephalitis.

PubMed

Pakozdy, Akos; Glantschnigg, Ursula; Leschnik, Michael; Hechinger, Harald; Moloney, Teresa; Lang, Bethan; Halasz, Peter; Vincent, Angela

2014-03-01

A 5-year-old, female client-owned cat presented with acute onset of focal epileptic seizures with orofacial twitching and behavioural changes. Magnetic resonance imaging showed bilateral temporal lobe hyperintensities and the EEG was consistent with ictal epileptic seizure activity. After antiepileptic and additional corticosteroid treatment, the cat recovered and by 10 months of follow-up was seizure-free without any problem. Retrospectively, antibodies to LGI1, a component of the voltage-gated potassium channel-complex, were identified. Feline focal seizures with orofacial involvement have been increasingly recognised in client-owned cats, and autoimmune limbic encephalitis was recently suggested as a possible aetiology. This is the first report of EEG, MRI and long-term follow-up of this condition in cats which is similar to human limbic encephalitis.

Limbic encephalitis presenting as a post-partum psychiatric condition.

PubMed

Gotkine, Marc; Ben-Hur, Tamir; Vincent, Angela; Vaknin-Dembinsky, Adi

2011-09-15

We describe a woman who presented with a psychiatric disorder post-partum and subsequently developed seizures and cognitive dysfunction prompting further investigation. A diagnosis of limbic encephalitis (LE) was made and antibodies to voltage-gated potassium channel complex (VGKC) detected. These antibodies are found in many non-paraneoplastic patients with LE. Although antibody-mediated conditions tend to present or relapse post-partum, VGKC-LE in the post-partum period has not been described. Case report. Clinical and imaging data were consistent with limbic encephalitis. High titres of anti-VGKC-complex antibodies confirmed the diagnosis of VGKC-LE. The similarities between the psychiatric symptomatology of VGKC-LE and post-partum psychiatric disorders raise the possibility that some instances of post-partum psychiatric conditions are manifestations of immune-mediated, non-paraneoplastic LE. Copyright © 2011 Elsevier B.V. All rights reserved.

Pathophysiological Alterations In The Basolateral Amygdala And Neurodegeneration Of Limbic Structures During Epileptogenesis Induced By Status Epilepticus

DTIC Science & Technology

2009-02-05

Crestani F, Martin JR, Möhler H, and Rudolph U (2000) Mechanism of action of the hypnotic zolpidem in vivo. Br J Pharmacol 131:1251–56...epilepsy laterality and reproductive hormone levels in women. Epilepsy Behav 4:407-13. Houser CR (1990) Granule cell dispersion in the dentate gyrus of...cortex from epileptic patients. Neurobiol Dis 8:459- 68. Kostarczyk EM (1986) The amygdala and male reproductive functions. I. Anatomical and

Treatment of anti-Ma2/Ta paraneoplastic syndrome.

PubMed

Kraker, Jessica

2009-01-01

The paraneoplastic syndrome caused by Ma2/Ta antibodies alone (not in conjunction with Ma1 or Ma3 antibodies) varies in presentation from classic limbic encephalitis. The Ma2 syndrome may present with symptoms referable to the brainstem, diencephalon, and limbic system. These clinical symptoms are accompanied by MRI changes and abnormal electroencephalographic findings. It is important to recognize when the encephalitic syndrome is secondary to Ma2 paraneoplastic antibodies, as the patients improve or stabilize most often when the underlying carcinoma is treated. Treatment of the paraneoplastic syndrome begins with recognition of the symptoms, such as memory impairment, seizures, sleep disturbances, bradykinesia or hypokinesia, and eye movement abnormalities. If a primary tumor is discovered during the workup, it should be removed and treated with the most up-to-date oncologic treatment available. In addition to oncologic treatment, the syndrome may be treated with an immunosuppressant regimen to optimize the neurologic outcome. Leaving the patient untreated will result in decline and eventual death from the cancer itself or from complications of the paraneoplastic syndrome.

Paraneoplastic limbic encephalitis associated with mixed olfactory neuroblastoma and craniopharyngioma: A case report and literature review.

PubMed

Nagafuji, Hiroshi; Yokoi, Hidenori; Fujiwara, Masachika; Sato, Dai; Saito, Koichiro

2018-06-01

Paraneoplastic limbic encephalitis (PLE) is a rare disorder of the nervous system associated with malignant disease. It has a subacute onset with the following symptoms: cognitive dysfunction, seizures, irritability, hallucinations, and short-term memory loss. Herein, we report the case of a 35-year-old man with PLE, an olfactory neuroblastoma (ONB) admixed with craniopharyngioma, and serum anti-Hu antibodies. The patient presented with generalized seizures, short-term memory loss, and a polypoid mass located high in the nasal cavity. He underwent surgical resection of the tumor and postoperative chemoradiotherapy with concurrent intra-arterial cisplatin administration. Pathological examination indicated an ONB admixed with craniopharyngioma. The patient's neurological symptoms gradually diminished after surgery. No evidence of recurrence was observed during a 4-year follow-up. We reported a histologically unusual heterogeneous tumor that comprised ONB and craniopharyngioma. This is the first reported case of PLE with anti-Hu antibodies possibly associated with ONB admixed with craniopharyngioma.

[VGKC antibodies associated with limbic encephalitis].

PubMed

Soeder, B M; Urbach, H; Elger, C E; Bien, C G; Beyenburg, S

2005-06-01

Since the initial description of limbic encephalitis (LE) in 1960/1968, several subforms of this clinico-neuropathological syndrome have been identified. The best known is paraneoplastic LE. However, non-paraneoplastic forms have been reported, too. Very recently, autoantibodies against voltage-gated potassium channels have been described in association with LE. The diagnostic workup of such a case and the apparently typical good response to long-term immunotherapy of this LE subform are described.

From Serpent to CEO: Improving First-Term Security Forces Airman Performance Through Neuroscience Education

DTIC Science & Technology

2017-06-09

full ability to inhibit ANS and limbic response are prone to be impulsive, 25 unintentional, or hesitant when faced with high -threat decisions...graduate degrees in Criminal Justice, a Graduate Certificate in Organizational Leadership, and a current American Society for Industrial Security...experience and full ability to inhibit ANS and limbic response are prone to be impulsive, unintentional, or hesitant when faced with high -threat

Autoimmune limbic encephalitis with anti-contactin-associated protein-like 2 antibody secondary to pembrolizumab therapy.

PubMed

Brown, Michael P; Hissaria, Pravin; Hsieh, Amy Hc; Kneebone, Christopher; Vallat, Wilson

2017-04-15

Immune checkpoint inhibitors such as Pembrolizumab are used to restore antitumour immune response. It is important to be vigilant of immune mediated adverse events related to such therapy. We report a case of autoimmune limbic encephalitis with Contactin-Associated Protein-like 2 (CASPR2) antibody secondary to Pembrolizumab therapy for metastatic melanoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-averaging in complex brain neuron signals

NASA Astrophysics Data System (ADS)

Bershadskii, A.; Dremencov, E.; Fukayama, D.; Yadid, G.

2002-12-01

Nonlinear statistical properties of Ventral Tegmental Area (VTA) of limbic brain are studied in vivo. VTA plays key role in generation of pleasure and in development of psychological drug addiction. It is shown that spiking time-series of the VTA dopaminergic neurons exhibit long-range correlations with self-averaging behavior. This specific VTA phenomenon has no relation to VTA rewarding function. Last result reveals complex role of VTA in limbic brain.

Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats: A Manganese-Enhanced MRI and Behavioral Study.

PubMed

Ouyang, Jessica; Pace, Edward; Lepczyk, Laura; Kaufman, Michael; Zhang, Jessica; Perrine, Shane A; Zhang, Jinsheng

2017-07-07

Blast-induced tinitus is the number one service-connected disability that currently affects military personnel and veterans. To elucidate its underlying mechanisms, we subjected 13 Sprague Dawley adult rats to unilateral 14 psi blast exposure to induce tinnitus and measured auditory and limbic brain activity using manganese-enhanced MRI (MEMRI). Tinnitus was evaluated with a gap detection acoustic startle reflex paradigm, while hearing status was assessed with prepulse inhibition (PPI) and auditory brainstem responses (ABRs). Both anxiety and cognitive functioning were assessed using elevated plus maze and Morris water maze, respectively. Five weeks after blast exposure, 8 of the 13 blasted rats exhibited chronic tinnitus. While acoustic PPI remained intact and ABR thresholds recovered, the ABR wave P1-N1 amplitude reduction persisted in all blast-exposed rats. No differences in spatial cognition were observed, but blasted rats as a whole exhibited increased anxiety. MEMRI data revealed a bilateral increase in activity along the auditory pathway and in certain limbic regions of rats with tinnitus compared to age-matched controls. Taken together, our data suggest that while blast-induced tinnitus may play a role in auditory and limbic hyperactivity, the non-auditory effects of blast and potential traumatic brain injury may also exert an effect.

An fMRI study of the brain responses of traumatized mothers to viewing their toddlers during separation and play.

PubMed

Schechter, Daniel S; Moser, Dominik A; Wang, Zhishun; Marsh, Rachel; Hao, XueJun; Duan, Yunsuo; Yu, Shan; Gunter, Benjamin; Murphy, David; McCaw, Jaime; Kangarlu, Alayar; Willheim, Erica; Myers, Michael M; Hofer, Myron A; Peterson, Bradley S

2012-11-01

This study tested whether mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) vs healthy controls (HC) would show greater limbic and less frontocortical activity when viewing young children during separation compared to quiet play. Mothers of 20 children (12-42 months) participated: 11 IPV-PTSD mothers and 9 HC with no PTSD. During fMRI, mothers watched epochs of play and separation from their own and unfamiliar children. The study focused on comparison of PTSD mothers vs HC viewing children in separation vs play, and viewing own vs unfamiliar children in separation. Both groups showed distinct patterns of brain activation in response to viewing children in separation vs play. PTSD mothers showed greater limbic and less frontocortical activity (BA10) than HC. PTSD mothers also reported feeling more stressed than HC when watching own and unfamiliar children during separation. Their self-reported stress was associated with greater limbic and less frontocortical activity. Both groups also showed distinct patterns of brain activation in response to viewing their own vs unfamiliar children during separation. PTSD mothers' may not have access to frontocortical regulation of limbic response upon seeing own and unfamiliar children in separation. This converges with previously reported associations of maternal IPV-PTSD and atypical caregiving behavior following separation.

Limbic striatal dopamine D2/3 receptor availability is associated with non-planning impulsivity in healthy adults after exclusion of potential dissimulators.

PubMed

Reeves, Suzanne J; Polling, Catherine; Stokes, Paul R A; Lappin, Julia M; Shotbolt, Paul P; Mehta, Mitul A; Howes, Oliver D; Egerton, Alice

2012-04-30

Positron emission tomography (PET) studies have reported an association between reduced striatal dopamine D2/3 receptor availability and higher scores on self-report measures of trait impulsivity in healthy adults. However, impulsivity is a multi-faceted construct, and it is unclear which aspect(s) of impulsivity might be driving these associations. The current study aimed to investigate the relationship between limbic (ventral) striatal D2/3 receptor availability and individual components of impulsivity (attentional, motor and non-planning) using the Barratt Impulsiveness Scale (BIS-11) and [(11)C]raclopride PET in 23 healthy volunteers. A partial correlational analysis showed a significant association between non-planning impulsiveness (lack of forethought or 'futuring') and limbic D2/3 receptor availability, which was only apparent after the exclusion of potential dissimulators (indexed by high scores on impression management). Our findings suggest that non-planning impulsiveness is associated with individual variation in limbic striatal D2/3 receptor availability and that different facets of impulsivity may have specific neurochemical correlates. Future studies that combine D2/3 receptor imaging with behavioral measures of impulsivity are required to further elucidate the precise relationship between individual components of trait impulsivity and brain dopaminergic function. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[Autoimmune Associated Encephalitis and Dementia].

PubMed

Watanabe, Osamu

2016-04-01

Antibodies against various neural surface antigens induce cognitive impairments. Anti-VGKC (voltage gated potassium channel) complex antibodies are well known as one of the causative autoantibodies. An anti-VGKC antibody was identified as the autoantibody in acquired neuromyotonia (Isaacs' syndrome), which causes muscle cramps and difficulty in opening the palm of the hands. However, this antibody also tests positive in autoimmune limbic encephalitis, which has a subacute progress and causes poor memory or epilepsy attacks. Typical cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures. In recent years, the true target antigens of the anti-VGKC antibody of this VGKC limbic encephalitis have been recognized as leucine rich glioma inactivated protein (LGI)-1 and others. These antibodies to amnesia-related LGI-1 in limbic encephalitis neutralize the LGI-1-ADAM22 (an anchor protein) interaction and reduce synaptic AMPA receptors. There have been reports of limbic encephalitis associated with anti-VGKC complex antibodies mimicking Creutzfeldt-Jakob disease (CJD). Less than 2% of the patients with sporadic CJD (sCJD) develop serum anti-VGKC complex antibodies and, when positive, only at low titres. Low titres of these antibodies occur only rarely in suspected patients with sCJD, and when present, should be interpreted with caution.

Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis.

PubMed

Kelley, B P; Patel, S C; Marin, H L; Corrigan, J J; Mitsias, P D; Griffith, B

2017-06-01

Autoimmune encephalitis is a relatively new category of immune-mediated disease involving the central nervous system that demonstrates a widely variable spectrum of clinical presentations, ranging from the relatively mild or insidious onset of cognitive impairment to more complex forms of encephalopathy with refractory seizure. Due to its diverse clinical features, which can mimic a variety of other pathologic processes, autoimmune encephalitis presents a diagnostic challenge to clinicians. Imaging findings in patients with these disorders can also be quite variable, but recognizing characteristic findings within limbic structures suggestive of autoimmune encephalitis can be a key step in alerting clinicians to the potential diagnosis and ensuring a prompt and appropriate clinical work-up. In this article, we review antibody-mediated encephalitis and its various subtypes with a specific emphasis on the role of neuroimaging in the diagnostic work-up. © 2017 by American Journal of Neuroradiology.

Towards a neural basis of music-evoked emotions.

PubMed

Koelsch, Stefan

2010-03-01

Music is capable of evoking exceptionally strong emotions and of reliably affecting the mood of individuals. Functional neuroimaging and lesion studies show that music-evoked emotions can modulate activity in virtually all limbic and paralimbic brain structures. These structures are crucially involved in the initiation, generation, detection, maintenance, regulation and termination of emotions that have survival value for the individual and the species. Therefore, at least some music-evoked emotions involve the very core of evolutionarily adaptive neuroaffective mechanisms. Because dysfunctions in these structures are related to emotional disorders, a better understanding of music-evoked emotions and their neural correlates can lead to a more systematic and effective use of music in therapy. Copyright 2010 Elsevier Ltd. All rights reserved.

A Functional MRI Study of Happy and Sad Emotions in Music with and without Lyrics.

PubMed

Brattico, Elvira; Alluri, Vinoo; Bogert, Brigitte; Jacobsen, Thomas; Vartiainen, Nuutti; Nieminen, Sirke; Tervaniemi, Mari

2011-01-01

Musical emotions, such as happiness and sadness, have been investigated using instrumental music devoid of linguistic content. However, pop and rock, the most common musical genres, utilize lyrics for conveying emotions. Using participants' self-selected musical excerpts, we studied their behavior and brain responses to elucidate how lyrics interact with musical emotion processing, as reflected by emotion recognition and activation of limbic areas involved in affective experience. We extracted samples from subjects' selections of sad and happy pieces and sorted them according to the presence of lyrics. Acoustic feature analysis showed that music with lyrics differed from music without lyrics in spectral centroid, a feature related to perceptual brightness, whereas sad music with lyrics did not diverge from happy music without lyrics, indicating the role of other factors in emotion classification. Behavioral ratings revealed that happy music without lyrics induced stronger positive emotions than happy music with lyrics. We also acquired functional magnetic resonance imaging data while subjects performed affective tasks regarding the music. First, using ecological and acoustically variable stimuli, we broadened previous findings about the brain processing of musical emotions and of songs versus instrumental music. Additionally, contrasts between sad music with versus without lyrics recruited the parahippocampal gyrus, the amygdala, the claustrum, the putamen, the precentral gyrus, the medial and inferior frontal gyri (including Broca's area), and the auditory cortex, while the reverse contrast produced no activations. Happy music without lyrics activated structures of the limbic system and the right pars opercularis of the inferior frontal gyrus, whereas auditory regions alone responded to happy music with lyrics. These findings point to the role of acoustic cues for the experience of happiness in music and to the importance of lyrics for sad musical emotions.

Gender differences in alpha-[(11)C]MTrp brain trapping, an index of serotonin synthesis, in medication-free individuals with major depressive disorder: a positron emission tomography study.

PubMed

Frey, Benicio N; Skelin, Ivan; Sakai, Yojiro; Nishikawa, Masami; Diksic, Mirko

2010-08-30

Women are at higher risk than men for developing major depressive disorder (MDD), but the mechanisms underlying this higher risk are unknown. Here, we report proportionally normalized alpha-[(11)C]methyl-L-tryptophan brain trapping constant (alpha-[(11)C]MTrp K*(N)), an index of serotonin synthesis, in 25 medication-free individuals with MDD and in 25 gender- and age-matched healthy subjects who were studied using positron emission tomography (PET). Comparisons of alpha-[(11)C]MTrp K*(N) values between the men and women were conducted at the voxel and cluster levels using Statistical Parametric Mapping 2 (SPM2) analysis. In addition, the alpha-[(11)C]MTrp K*(N) values on both sides of the brain were extracted and compared to identify the left to right differences, as well as the gender differences. Women with MDD displayed higher alpha-[(11)C]MTrp K*(N) than men in the inferior frontal gyrus, anterior cingulate cortex (ACC), parahippocampal gyrus, precuneus, superior parietal lobule, and occipital lingual gyrus. In a matched group of normal subjects the gender differences were opposite from those found in MDD patients. Significant hemispheric differences in fronto-limbic structures between men and women with MDD were also observed. The K*(N) extracted from the volumes identified in MDD patients and in male and female normal subjects suggested no significant differences between males and females. In conclusion, depressed women have higher serotonin synthesis in multiple regions of the prefrontal cortex and limbic system involved with mood regulation, as compared with depressed men. Gender differences in brain serotonin synthesis may be related to higher risk for MDD in women. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

A Functional MRI Study of Happy and Sad Emotions in Music with and without Lyrics

PubMed Central

Brattico, Elvira; Alluri, Vinoo; Bogert, Brigitte; Jacobsen, Thomas; Vartiainen, Nuutti; Nieminen, Sirke; Tervaniemi, Mari

2011-01-01

Musical emotions, such as happiness and sadness, have been investigated using instrumental music devoid of linguistic content. However, pop and rock, the most common musical genres, utilize lyrics for conveying emotions. Using participants’ self-selected musical excerpts, we studied their behavior and brain responses to elucidate how lyrics interact with musical emotion processing, as reflected by emotion recognition and activation of limbic areas involved in affective experience. We extracted samples from subjects’ selections of sad and happy pieces and sorted them according to the presence of lyrics. Acoustic feature analysis showed that music with lyrics differed from music without lyrics in spectral centroid, a feature related to perceptual brightness, whereas sad music with lyrics did not diverge from happy music without lyrics, indicating the role of other factors in emotion classification. Behavioral ratings revealed that happy music without lyrics induced stronger positive emotions than happy music with lyrics. We also acquired functional magnetic resonance imaging data while subjects performed affective tasks regarding the music. First, using ecological and acoustically variable stimuli, we broadened previous findings about the brain processing of musical emotions and of songs versus instrumental music. Additionally, contrasts between sad music with versus without lyrics recruited the parahippocampal gyrus, the amygdala, the claustrum, the putamen, the precentral gyrus, the medial and inferior frontal gyri (including Broca’s area), and the auditory cortex, while the reverse contrast produced no activations. Happy music without lyrics activated structures of the limbic system and the right pars opercularis of the inferior frontal gyrus, whereas auditory regions alone responded to happy music with lyrics. These findings point to the role of acoustic cues for the experience of happiness in music and to the importance of lyrics for sad musical emotions. PMID:22144968

Limbic Justice—Amygdala Involvement in Immediate Rejection in the Ultimatum Game

PubMed Central

Fransson, Peter; Petrovic, Predrag; Johannesson, Magnus; Ingvar, Martin

2011-01-01

Imaging studies have revealed a putative neural account of emotional bias in decision making. However, it has been difficult in previous studies to identify the causal role of the different sub-regions involved in decision making. The Ultimatum Game (UG) is a game to study the punishment of norm-violating behavior. In a previous influential paper on UG it was suggested that frontal insular cortex has a pivotal role in the rejection response. This view has not been reconciled with a vast literature that attributes a crucial role in emotional decision making to a subcortical structure (i.e., amygdala). In this study we propose an anatomy-informed model that may join these views. We also present a design that detects the functional anatomical response to unfair proposals in a subcortical network that mediates rapid reactive responses. We used a functional MRI paradigm to study the early components of decision making and challenged our paradigm with the introduction of a pharmacological intervention to perturb the elicited behavioral and neural response. Benzodiazepine treatment decreased the rejection rate (from 37.6% to 19.0%) concomitantly with a diminished amygdala response to unfair proposals, and this in spite of an unchanged feeling of unfairness and unchanged insular response. In the control group, rejection was directly linked to an increase in amygdala activity. These results allow a functional anatomical detection of the early neural components of rejection associated with the initial reactive emotional response. Thus, the act of immediate rejection seems to be mediated by the limbic system and is not solely driven by cortical processes, as previously suggested. Our results also prompt an ethical discussion as we demonstrated that a commonly used drug influences core functions in the human brain that underlie individual autonomy and economic decision making. PMID:21559322

From Anxious to Reckless: A Control Systems Approach Unifies Prefrontal-Limbic Regulation Across the Spectrum of Threat Detection.

PubMed

Mujica-Parodi, Lilianne R; Cha, Jiook; Gao, Jonathan

2017-01-01

Here we provide an integrative review of basic control circuits, and introduce techniques by which their regulation can be quantitatively measured using human neuroimaging. We illustrate the utility of the control systems approach using four human neuroimaging threat detection studies ( N = 226), to which we applied circuit-wide analyses in order to identify the key mechanism underlying individual variation. In so doing, we build upon the canonical prefrontal-limbic control system to integrate circuit-wide influence from the inferior frontal gyrus (IFG). These were incorporated into a computational control systems model constrained by neuroanatomy and designed to replicate our experimental data. In this model, the IFG acts as an informational set point, gating signals between the primary prefrontal-limbic negative feedback loop and its cortical information-gathering loop. Along the cortical route, if the sensory cortex provides sufficient information to make a threat assessment, the signal passes to the ventromedial prefrontal cortex (vmPFC), whose threat-detection threshold subsequently modulates amygdala outputs. However, if signal outputs from the sensory cortex do not provide sufficient information during the first pass, the signal loops back to the sensory cortex, with each cycle providing increasingly fine-grained processing of sensory data. Simulations replicate IFG (chaotic) dynamics experimentally observed at both ends at the threat-detection spectrum. As such, they identify distinct types of IFG disconnection from the circuit, with associated clinical outcomes. If IFG thresholds are too high, the IFG and sensory cortex cycle for too long; in the meantime the coarse-grained (excitatory) pathway will dominate, biasing ambiguous stimuli as false positives. On the other hand, if cortical IFG thresholds are too low, the inhibitory pathway will suppress the amygdala without cycling back to the sensory cortex for much-needed fine-grained sensory cortical data, biasing ambiguous stimuli as false negatives. Thus, the control systems model provides a consistent mechanism for IFG regulation, capable of producing results consistent with our data for the full spectrum of threat-detection: from fearful to optimal to reckless. More generally, it illustrates how quantitative characterization of circuit dynamics can be used to unify a fundamental dimension across psychiatric affective symptoms, with implications for populations that range from anxiety disorders to addiction.

Neural Alterations in Acquired Age-Related Hearing Loss

PubMed Central

Mudar, Raksha A.; Husain, Fatima T.

2016-01-01

Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although, we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches. PMID:27313556

A Preliminary Study of DBH (Encoding Dopamine Beta-Hydroxylase) Genetic Variation and Neural Correlates of Emotional and Motivational Processing in Individuals With and Without Pathological Gambling.

PubMed

Yang, Bao-Zhu; Balodis, Iris M; Lacadie, Cheryl M; Xu, Jiansong; Potenza, Marc N

2016-06-01

Background and aims Corticostriatal-limbic neurocircuitry, emotional and motivational processing, dopaminergic and noradrenergic systems and genetic factors have all been implicated in pathological gambling (PG). However, allelic variants of genes influencing dopaminergic and noradrenergic neurotransmitters have not been investigated with respect to the neural correlates of emotional and motivational states in PG. Dopamine beta-hydroxylase (DBH) converts dopamine to norepinephrine; the T allele of a functional single-nucleotide polymorphism rs1611115 (C-1021T) in the DBH gene is associated with less DBH activity and has been linked to emotional processes and addiction. Here, we investigate the influence of rs1611115 on the neural correlates of emotional and motivational processing in PG and healthy comparison (HC) participants. Methods While undergoing functional magnetic resonance imaging, 18 PG and 25 HC participants, all European Americans, viewed gambling-, sad-, and cocaine-related videotapes. Analyses focused on brain activation differences related to DBH genotype (CC/T-carrier [i.e., CT and TT]) and condition (sad/gambling/cocaine). Results CC participants demonstrated greater recruitment of corticostriatal-limbic regions, relative to T-carriers. DBH variants were also associated with altered corticostriatal-limbic activations across the different videotape conditions, and this association appeared to be driven by greater activation in CC participants relative to T-carriers during the sad condition. CC relative to T-carrier subjects also reported greater subjective sadness to the sad videotapes. Conclusions Individual differences in genetic composition linked to aminergic function contribute significantly to emotional regulation across diagnostic groups and warrant further investigation in PG.

A diffusional kurtosis imaging study of idiopathic generalized epilepsy with unilateral interictal epileptiform discharges in children.

PubMed

Zhang, Yuzhen; Gao, Yu; Zhou, Minxiong; Wu, Jie; Zee, Chishing; Wang, Dengbin

2016-10-01

To investigate brain abnormalities in children with a clinical diagnosis of idiopathic generalized epilepsy (IGE) and unilateral interictal epileptiform discharges (IED) demonstrated on electroencephalography (EEG) by diffusional kurtosis imaging (DKI). DKI images were obtained from 18 patients (n=9 each in the left and right hemispheres). Fractional anisotropy (FA), mean diffusivity (MD), and mean kurtosis (MK) maps were estimated through voxel-based analyses, and compared with 18 normal controls matched for age and sex. In the left side group, the significant differences of FA were in the left fusiform gyrus and occipital lobe of the white matter (WM). The significant differences of MD were in the left pons. The significant differences of MK were in the anterior cingulate gyrus, limbic lobe, gray matter (GM) and WM of the right cerebrum. In the right side group, the significant differences of FA were in the WM of the left cerebrum. MD identified differences in the frontal, temporal, occipital, and parietal lobes of both hemispheres, especially in the limbic system, fusiform gyrus, uncus, and parahippocampal gyrus. The significant differences of MK were in the GM of the right cerebrum, particularly in the rolandic operculum and frontal lobe. DKI is sensitive for the detection of diffusion abnormalities in both WM and GM of IGE in children. Secondary brain abnormalities may exist in regions outside the unilateral epileptogenic zone through the limbic epileptic network, and can be detected by DKI indices FA, MD and MK. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease

PubMed Central

Weber, Bernd; Schoene-Bake, Jan-Christoph; Roeske, Sandra; Mirbach, Sandra; Anspach, Christian; Schneider-Gold, Christiane; Betz, Regina C.; Helmstaedter, Christoph; Tittgemeyer, Marc; Klockgether, Thomas; Kornblum, Cornelia

2011-01-01

Myotonic dystrophy types 1 and 2 are progressive multisystemic disorders with potential brain involvement. We compared 22 myotonic dystrophy type 1 and 22 myotonic dystrophy type 2 clinically and neuropsychologically well-characterized patients and a corresponding healthy control group using structural brain magnetic resonance imaging at 3 T (T1/T2/diffusion-weighted). Voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics were applied for voxel-wise analysis of cerebral grey and white matter affection (Pcorrected < 0.05). We further examined the association of structural brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were more prominent in patients with myotonic dystrophy type 1 with less white matter affection (early disease stages), contrary to patients with myotonic dystrophy type 2. Thus, depression in myotonic dystrophies might be a reactive adjustment disorder rather than a direct consequence of structural brain damage. Associations of white matter affection with age/disease duration as well as patterns of cerebral water diffusion parameters pointed towards an ongoing process of myelin destruction and/or axonal loss in our cross-sectional study design. Our data suggest that both myotonic dystrophy types 1 and 2 are serious white matter diseases with prominent callosal body and limbic system affection. White matter changes dominated the extent of grey matter changes, which might argue against Wallerian degeneration as the major cause of white matter affection in myotonic dystrophies. PMID:22131273

Serotonin Receptors in Hippocampus

PubMed Central

Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

2012-01-01

Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

Emotional Intelligence: Advocating for the Softer Side of Leadership

DTIC Science & Technology

2013-03-01

handles social rejection and physical pain.30 In one study , patients in fMRI machines were told they were playing a game with two other players — a...operated more freely.”43 Yet these results do not indicate the cognitive system can be allowed to take a backseat. In another study , fMRI showed that...The roots of empathy can be found at an early age, which implies empathy is hardwired into the primitive limbic system. One study observed a toddler

Understanding heterogeneity in grey matter research of adults with childhood maltreatment-A meta-analysis and review.

PubMed

Paquola, Casey; Bennett, Maxwell R; Lagopoulos, Jim

2016-10-01

Childhood trauma has been associated with long term effects on prefrontal-limbic grey matter. A literature search was conducted to identify structural magnetic resonance imaging studies of adults with a history of childhood trauma. We performed three meta-analyses. Hedges' g effect sizes were calculated for each study providing hippocampal or amygdala volumes of trauma and non-trauma groups. Seed based differential mapping was utilised to synthesise whole brain voxel based morphometry (VBM) studies. A total of 38 articles (17 hippocampus, 13 amygdala, 19 whole brain VBM) were included in the meta-analyses. Trauma cohorts exhibited smaller hippocampus and amygdala volumes bilaterally. The most robust findings of the whole brain VBM meta-analysis were reduced grey matter in the right dorsolateral prefrontal cortex and right hippocampus amongst adults with a history of childhood trauma. Subgroup analyses and meta-regressions showed results were moderated by age, gender, the cohort's psychiatric health and the study's definition of childhood trauma. We provide evidence of abnormal grey matter in prefrontal-limbic brain regions of adults with a history of childhood maltreatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Beyond stereotypes of adolescent risk taking: Placing the adolescent brain in developmental context☆

PubMed Central

Romer, Daniel; Reyna, Valerie F.; Satterthwaite, Theodore D.

2017-01-01

Recent neuroscience models of adolescent brain development attribute the morbidity and mortality of this period to structural and functional imbalances between more fully developed limbic regions that subserve reward and emotion as opposed to those that enable cognitive control. We challenge this interpretation of adolescent development by distinguishing risk-taking that peaks during adolescence (sensation seeking and impulsive action) from risk taking that declines monotonically from childhood to adulthood (impulsive choice and other decisions under known risk). Sensation seeking is primarily motivated by exploration of the environment under ambiguous risk contexts, while impulsive action, which is likely to be maladaptive, is more characteristic of a subset of youth with weak control over limbic motivation. Risk taking that declines monotonically from childhood to adulthood occurs primarily under conditions of known risks and reflects increases in executive function as well as aversion to risk based on increases in gist-based reasoning. We propose an alternative Lifespan Wisdom Model that highlights the importance of experience gained through exploration during adolescence. We propose, therefore, that brain models that recognize the adaptive roles that cognition and experience play during adolescence provide a more complete and helpful picture of this period of development. PMID:28777995

Treatment responsive GABA(B)-receptor limbic encephalitis presenting as new-onset super-refractory status epilepticus (NORSE) in a deployed U.S. soldier.

PubMed

Hainsworth, Jeffrey Brian; Shishido, Akira; Theeler, Brett James; Carroll, Craig Grason; Fasano, Rebecca Ellen

2014-12-01

A 23-year-old, previously healthy, deployed U.S. soldier presented with bilateral temporal lobe seizures recalcitrant to multiple antiepileptic drugs and anti-seizure anaesthetic agents. He received methylprednisolone, intravenous immunoglobulins, plasma exchange, and rituximab for presumed autoimmune encephalitis before achieving seizure freedom. Six weeks after presentation, the aetiology of his refractory seizures was found to be due to autoantibodies targeting the anti-GABA(B)-receptor. This case is noteworthy for being the first reported case of anti-GABA(B)-receptor limbic encephalitis presenting with new-onset refractory status epilepticus (NORSE), a clinical syndrome that often carries a grave prognosis and in which a treatable aetiology is often never discovered. Our case also supports testing for GABA-receptor autoantibodies and the upfront use of multi-modal immunotherapy in patients presenting with limbic encephalitis and new refractory seizures.

Density and distribution of hippocampal neurotransmitter receptors in autism: an autoradiographic study.

PubMed

Blatt, G J; Fitzgerald, C M; Guptill, J T; Booker, A B; Kemper, T L; Bauman, M L

2001-12-01

Neuropathological studies in autistic brains have shown small neuronal size and increased cell packing density in a variety of limbic system structures including the hippocampus, a change consistent with curtailment of normal development. Based on these observations in the hippocampus, a series of quantitative receptor autoradiographic studies were undertaken to determine the density and distribution of eight types of neurotransmitter receptors from four neurotransmitter systems (GABAergic, serotoninergic [5-HT], cholinergic, and glutamatergic). Data from these single concentration ligand binding studies indicate that the GABAergic receptor system (3[H]-flunitrazepam labeled benzodiazepine binding sites and 3[H]-muscimol labeled GABA(A) receptors) is significantly reduced in high binding regions, marking for the first time an abnormality in the GABA system in autism. In contrast, the density and distribution of the other six receptors studied (3[H]-80H-DPAT labeled 5-HT1A receptors, 3[H]-ketanserin labeled 5-HT2 receptors, 3[H]-pirenzepine labled M1 receptors, 3[H]-hemicholinium labeled high affinity choline uptake sites, 3[H]-MK801 labeled NMDA receptors, and 3[H]-kainate labeled kainate receptors) in the hippocampus did not demonstrate any statistically significant differences in binding.

The volumetric and shape changes of the putamen and thalamus in first episode, untreated major depressive disorder.

PubMed

Lu, Yi; Liang, Hongmin; Han, Dan; Mo, Yin; Li, Zongfang; Cheng, Yuqi; Xu, Xiufeng; Shen, Zonglin; Tan, Chunyan; Zhao, Wei; Zhu, Yun; Sun, Xuejin

2016-01-01

Previous MRI studies confirmed abnormalities in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) network or limbic-cortico-striatal-thalamic-cortical (LCSTC) circuits in patients with major depressive disorder (MDD), but few studies have investigated the subcortical structural abnormalities. Therefore, we sought to determine whether focal subcortical grey matter (GM) changes might be present in MDD at an early stage. We recruited 30 first episode, untreated patients with major depressive disorder (MDD) and 26 healthy control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetric and shape analyses were used to assess volume and shape changes of the subcortical GM structures, respectively. In addition, probabilistic tractography methods were used to demonstrate the relationship between the subcortical and the cortical GM. Compared to healthy controls, MDD patients had significant volume reductions in the bilateral putamen and left thalamus (FWE-corrected, p < 0.05). Meanwhile, the vertex-based shape analysis showed regionally contracted areas on the dorsolateral and ventromedial aspects of the bilateral putamen, and on the dorsal and ventral aspects of left thalamus in MDD patients (FWE-corrected, p < 0.05). Additionally, a negative correlation was found between local atrophy in the dorsal aspects of the left thalamus and clinical variables representing severity. Furthermore, probabilistic tractography demonstrated that the area of shape deformation of the bilateral putamen and left thalamus have connections with the frontal and temporal lobes, which were found to be related to major depression. Our results suggested that structural abnormalities in the putamen and thalamus might be present in the early stages of MDD, which support the role of subcortical structure in the pathophysiology of MDD. Meanwhile, the present study showed that these subcortical structural abnormalities might be the potential trait markers of MDD.

Developmental effects of androgens in the human brain.

PubMed

Nguyen, T-V

2018-02-01

Neuroendocrine theories of brain development posit that androgens play a crucial role in sex-specific cortical growth, although little is known about the differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico-limbic development and cognition during adolescence. In this context, the National Institutes of Health Study of Normal Brain Development, a longitudinal study of typically developing children and adolescents aged 4-24 years (n=433), offers a unique opportunity to examine the developmental effects of androgens on cortico-limbic maturation and cognition. Using data from this sample, our group found that higher testosterone levels were associated with left-sided decreases in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal cortex, compared to right-sided increases in CTh in somatosensory areas in pre-pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural covariance (considered to reflect structural connectivity) also varied according to testosterone levels, with the testosterone-related brain phenotype predicting higher aggression levels and lower executive function, particularly in boys. By contrast, DHEA was associated with a pre-pubertal increase in CTh of several regions involved in cognitive control in both boys and girls. Covariance within several cortico-amygdalar structural networks also varied as a function of DHEA levels, with the DHEA-related brain phenotype predicting improvements in visual attention in both boys and girls. DHEA-related cortico-hippocampal structural covariance, on the other hand, predicted higher scores on a test of working memory. Interestingly, there were significant interactions between testosterone and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of testosterone on brain structure. In sum, testosterone-related effects on the developing brain may lead to detrimental effects on cortical functions (ie, higher aggression and lower executive function), whereas DHEA-related effects may optimise cortical functions (ie, better attention and working memory), perhaps by decreasing the influence of amygdalar and hippocampal afferents on cortical functions. © 2017 British Society for Neuroendocrinology.

Neurophysiological maturation in adolescence - vulnerability and counteracting addiction to alcohol.

PubMed

Chwedorowicz, Roman; Skarżyński, Henryk; Pucek, Weronika; Studziński, Tadeusz

2017-03-22

The results of contemporary studies confirm the formation of two neural networks in the brain during the period of adolescence. The first is defined as emotional, located in the limbic system, develops earlier, quicker, and more intensively than the second one in the prefrontal cortex, called the judgement network, which fulfils the role of control and inhibition of emotional reactions. The domination of the emotional network in adolescence is manifested by hyperactivity of the limbic system, accompanied by intensified undertaking of courageous, reckless, risky, or even sometimes dangerous actions, so very characteristic in the maturation. The aim of the article is to present the state of the art in the field of latest achievements in experimental neurophysiology related to the maturation of the structural end functional processes in adolescents, and to alcohol vulnerability. Alcohol effect initiation starts in early adolescence, and therefore is connected with alcohol abuse and addiction in adulthood, which confirms the necessity for provision of an early prophylactic protection for juveniles, even before entering the phase of early adolescence. Some electrophysiological characteristics, such as low P3 amplitude of the Event-Related Potential (ERP) and Event-Related Oscillations (EROs), are manifested by their high risk offspring, and are considered to be biological markers (endophenotypes) of a predisposition to develop alcohol use disorders. Electroencephalographic oscillations induced within the range of the theta and delta waves (Event-Related Oscillation- ERO), considered as endophenotypes and markers of increased vulnerability for addiction, present three groups of genes and three types of neurotransmitters, with gamma aminobutyric acid, acetylcholine and glutamate as neurotransmitters in the central nervous system. A new research approach consisting in the application of electroencephalographic methods and techniques in developmental and genetic studies of the conditioning of varied vulnerability, and especially increased preferences for alcohol tasting and abuse in adolescence, provide unique possibilities for comprehensive and deepened studies which may contribute to the prevention of alcohol addiction, the genesis of which, to a great extent, is related with the effect of causative environmental and genetic factors during adolescent development.

The consolidation of inhibitory avoidance memory in mice depends on the intensity of the aversive stimulus: The involvement of the amygdala, dorsal hippocampus and medial prefrontal cortex.

PubMed

Canto-de-Souza, L; Mattioli, R

2016-04-01

Several studies using inhibitory avoidance models have demonstrated the importance of limbic structures, such as the amygdala, dorsal hippocampus and medial prefrontal cortex, in the consolidation of emotional memory. However, we aimed to investigate the role of the amygdala (AMG), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) of mice in the consolidation of step-down inhibitory avoidance and whether this avoidance would be conditioned relative to the intensity of the aversive stimulus. To test this, we bilaterally infused anisomycin (ANI-40μg/μl, a protein synthesis inhibitor) into one of these three brain areas in mice. These mice were then exposed to one of two different intensities (moderate: 0.5mA or intense: 1.5mA) in a step-down inhibitory avoidance task. We found that consolidation of both of the aversive experiences was mPFC dependent, while the AMG and DH were only required for the consolidation of the intense experience. We suggest that in moderately aversive situations, which do not represent a severe physical risk to the individual, the consolidation of aversive experiences does not depend on protein synthesis in the AMG or the DH, but only the mPFC. However, for intense aversive stimuli all three of these limbic structures are essential for the consolidation of the experience. Copyright © 2016 Elsevier Inc. All rights reserved.

The brain anatomy of attention-deficit/hyperactivity disorder in young adults - a magnetic resonance imaging study.

PubMed

Gehricke, Jean-G; Kruggel, Frithjof; Thampipop, Tanyaporn; Alejo, Sharina Dyan; Tatos, Erik; Fallon, James; Muftuler, L Tugan

2017-01-01

This is one of the first studies to examine the structural brain anatomy and connectivity associated with an ADHD diagnosis and child as well as adult ADHD symptoms in young adults. It was hypothesized that an adult ADHD diagnosis and in particular childhood symptoms, are associated with widespread changes in the brain macro- and microstructure, which can be used to develop a morphometric biomarker for ADHD. Voxel-wise linear regression models were used to examine structural and diffusion-weighted MRI data in 72 participants (31 young adults with ADHD and 41 controls without ADHD) in relation to diagnosis and the number of self-reported child and adult symptoms. Findings revealed significant associations between ADHD diagnosis and widespread changes to the maturation of white matter fiber bundles and gray matter density in the brain, such as structural shape changes (incomplete maturation) of the middle and superior temporal gyrus, and fronto-basal portions of both frontal lobes. ADHD symptoms in childhood showed the strongest association with brain macro- and microstructural abnormalities. At the brain circuitry level, the superior longitudinal fasciculus (SLF) and cortico-limbic areas are dysfunctional in individuals with ADHD. The morphometric findings predicted an ADHD diagnosis correctly up to 83% of all cases. An adult ADHD diagnosis and in particular childhood symptoms are associated with widespread micro- and macrostructural changes. The SLF and cortico-limbic findings suggest complex audio-visual, motivational, and emotional dysfunctions associated with ADHD in young adults. The sensitivity of the morphometric findings in predicting an ADHD diagnosis was sufficient, which indicates that MRI-based assessments are a promising strategy for the development of a biomarker.

Self-reference, emotion inhibition and somatosensory disturbance: preliminary investigation of network perturbations in conversion disorder.

PubMed

Monsa, R; Peer, M; Arzy, S

2018-06-01

Conversion disorder (CD), or functional neurological disorder, is manifested as a neurological disturbance that is not macroscopically visible on clinical structural neuroimaging and is instead ascribed to underlying psychological stress. Known for many years in neuropsychiatry, a comprehensive explanation of the way in which psychological stress leads to a neurological deficit of a structural-like origin is still lacking. We applied whole-brain network-based data-driven analyses on resting-state functional magnetic resonance imaging, recorded in seven patients with acute-onset, stroke-like CD with unilateral paresis and hypoesthesia as compared with 15 age-matched healthy controls. We used a clustering analysis to measure functional connectivity (FC) strength within 10 different brain networks, as well as between these networks. Finally, we tested FC of specific brain regions that are known to be involved in CD. We found a significant increase in FC strength only within the default-mode network (DMN), which manages self-referential processing. Examination of inter-connectivity between networks showed a structure of disturbed connectivity, which included decreased connectivity between the DMN and limbic/salience network, increased connectivity between the limbic/salience network and body-related temporo-parieto-occipital junction network, decreased connectivity between the temporo-parieto-occipital junction and memory-related medial temporal lobe, and decreased connectivity between the medial temporal lobe and sensorimotor network. Region-specific FC analysis showed increased connectivity between the hippocampus and DMN. These preliminary results of disturbances in brain networks related to memory, emotions and self-referential processing, and networks involved in motor planning and execution, suggest a role of these cognitive functions in the psychopathology of CD. © 2018 EAN.

Systematic review of the neural basis of social cognition in patients with mood disorders

PubMed Central

Cusi, Andrée M.; Nazarov, Anthony; Holshausen, Katherine; MacQueen, Glenda M.; McKinnon, Margaret C.

2012-01-01

Background This review integrates neuroimaging studies of 2 domains of social cognition — emotion comprehension and theory of mind (ToM) — in patients with major depressive disorder and bipolar disorder. The influence of key clinical and method variables on patterns of neural activation during social cognitive processing is also examined. Methods Studies were identified using PsycINFO and PubMed (January 1967 to May 2011). The search terms were “fMRI,” “emotion comprehension,” “emotion perception,” “affect comprehension,” “affect perception,” “facial expression,” “prosody,” “theory of mind,” “mentalizing” and “empathy” in combination with “major depressive disorder,” “bipolar disorder,” “major depression,” “unipolar depression,” “clinical depression” and “mania.” Results Taken together, neuroimaging studies of social cognition in patients with mood disorders reveal enhanced activation in limbic and emotion-related structures and attenuated activity within frontal regions associated with emotion regulation and higher cognitive functions. These results reveal an overall lack of inhibition by higher-order cognitive structures on limbic and emotion-related structures during social cognitive processing in patients with mood disorders. Critically, key variables, including illness burden, symptom severity, comorbidity, medication status and cognitive load may moderate this pattern of neural activation. Limitations Studies that did not include control tasks or a comparator group were included in this review. Conclusion Further work is needed to examine the contribution of key moderator variables and to further elucidate the neural networks underlying altered social cognition in patients with mood disorders. The neural networks underlying higher-order social cognitive processes, including empathy, remain unexplored in patients with mood disorders. PMID:22297065

Corticostriatal connectivity fingerprints: Probability maps based on resting-state functional connectivity.

PubMed

Jaspers, Ellen; Balsters, Joshua H; Kassraian Fard, Pegah; Mantini, Dante; Wenderoth, Nicole

2017-03-01

Over the last decade, structure-function relationships have begun to encompass networks of brain areas rather than individual structures. For example, corticostriatal circuits have been associated with sensorimotor, limbic, and cognitive information processing, and damage to these circuits has been shown to produce unique behavioral outcomes in Autism, Parkinson's Disease, Schizophrenia and healthy ageing. However, it remains an open question how abnormal or absent connectivity can be detected at the individual level. Here, we provide a method for clustering gross morphological structures into subregions with unique functional connectivity fingerprints, and generate network probability maps usable as a baseline to compare individual cases against. We used connectivity metrics derived from resting-state fMRI (N = 100), in conjunction with hierarchical clustering methods, to parcellate the striatum into functionally distinct clusters. We identified three highly reproducible striatal subregions, across both hemispheres and in an independent replication dataset (N = 100) (dice-similarity values 0.40-1.00). Each striatal seed region resulted in a highly reproducible distinct connectivity fingerprint: the putamen showed predominant connectivity with cortical and cerebellar sensorimotor and language processing areas; the ventromedial striatum cluster had a distinct limbic connectivity pattern; the caudate showed predominant connectivity with the thalamus, frontal and occipital areas, and the cerebellum. Our corticostriatal probability maps agree with existing connectivity data in humans and non-human primates, and showed a high degree of replication. We believe that these maps offer an efficient tool to further advance hypothesis driven research and provide important guidance when investigating deviant connectivity in neurological patient populations suffering from e.g., stroke or cerebral palsy. Hum Brain Mapp 38:1478-1491, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The brain anatomy of attention-deficit/hyperactivity disorder in young adults – a magnetic resonance imaging study

PubMed Central

Kruggel, Frithjof; Thampipop, Tanyaporn; Alejo, Sharina Dyan; Tatos, Erik; Fallon, James; Muftuler, L. Tugan

2017-01-01

Background This is one of the first studies to examine the structural brain anatomy and connectivity associated with an ADHD diagnosis and child as well as adult ADHD symptoms in young adults. It was hypothesized that an adult ADHD diagnosis and in particular childhood symptoms, are associated with widespread changes in the brain macro- and microstructure, which can be used to develop a morphometric biomarker for ADHD. Methods Voxel-wise linear regression models were used to examine structural and diffusion-weighted MRI data in 72 participants (31 young adults with ADHD and 41 controls without ADHD) in relation to diagnosis and the number of self-reported child and adult symptoms. Results Findings revealed significant associations between ADHD diagnosis and widespread changes to the maturation of white matter fiber bundles and gray matter density in the brain, such as structural shape changes (incomplete maturation) of the middle and superior temporal gyrus, and fronto-basal portions of both frontal lobes. ADHD symptoms in childhood showed the strongest association with brain macro- and microstructural abnormalities. At the brain circuitry level, the superior longitudinal fasciculus (SLF) and cortico-limbic areas are dysfunctional in individuals with ADHD. The morphometric findings predicted an ADHD diagnosis correctly up to 83% of all cases. Conclusion An adult ADHD diagnosis and in particular childhood symptoms are associated with widespread micro- and macrostructural changes. The SLF and cortico-limbic findings suggest complex audio-visual, motivational, and emotional dysfunctions associated with ADHD in young adults. The sensitivity of the morphometric findings in predicting an ADHD diagnosis was sufficient, which indicates that MRI-based assessments are a promising strategy for the development of a biomarker. PMID:28406942

Executive functions, impulsivity, and inhibitory control in adolescents: A structural equation model

PubMed Central

Fino, Emanuele; Melogno, Sergio; Iliceto, Paolo; D’Aliesio, Sara; Pinto, Maria Antonietta; Candilera, Gabriella; Sabatello, Ugo

2014-01-01

Background. Adolescence represents a critical period for brain development, addressed by neurodevelopmental models to frontal, subcortical-limbic, and striatal activation, a pattern associated with rise of impulsivity and deficits in inhibitory control. The present study aimed at studying the association between self-report measures of impulsivity and inhibitory control with executive function in adolescents, employing structural equation modeling. Method. Tests were administered to 434 high school students. Acting without thinking was measured through the Barratt Impulsiveness Scale and the Dickman Impulsivity Inventory, reward sensitivity through the Behavioral Activation System, and sensation seeking through the Zuckerman–Kuhlman–Aluja Personali- ty Questionnaire. Inhibitory control was assessed through the Behavioral Inhibition System. The performance at the Wisconsin Card Sorting Task indicated executive function. Three models were specified using Sample Covariance Matrix, and the estimated parameters using Maximum Likelihood. Results. In the final model, impulsivity and inhibitory control predicted executive function, but sensation seeking did not. The fit of the model to data was excellent. Conclusions. The hypothesis that inhibitory control and impulsivity are predictors of executive function was supported. Our results appear informative of the validity of self-report measures to examine the relation between impulsivity traits rather than others to regulatory function of cognition and behavior. PMID:25157298

[The clinical phenomenology of Rett's syndrome].

PubMed

Calderón-González, R; Calderón-Sepulveda, R F; Treviño-Welsh, J

1999-01-01

The work was done to facilitate the clinical diagnosis and understanding of Rett syndrome (RS) by grouping the symptoms and signs in areas of neurological disfunction. This is a retrospective, longitudinal and observational study of 30 young females whose clinical manifestations were grouped using a modified Fitzgerald et al. scale for motor and behavior evaluation of patients with RS. All patients were videotaped at least during one or several appointments during their follow-up for a period of 1 to 10 years. All patients and videotapes were reviewed independently by the three authors. We followed the clinical diagnostic criteria of classic RS, and grouped the symptoms and signs in 12 groups of clinical phenomenology that represented specific areas of central or peripheral nervous system involvement: 1) dementia syndrome (fronto-temporo-parietal and limbic dysfunction); 2) extrapyramidal syndrome (basal ganglia dysfunction); 3) respiratory function disorders (brain stem reticular system disfunction); 4) sleep disorders (reticular system and limbic dysfunction); 5) epilepsy (cortico-subcortical paroxysmal bioelectrical dysfunction); 6) lower motor neuron syndrome (neuropathic dysfunction and/or peripheral neuropathy); 7) body growth retardation; 8) tonic-postural skeletal deformities; 9) deficit of pain sensation (nociceptive deficit); 10) pseudobulbar dysfunction; 11) autonomic dysfunction and 12) others (microcephaly and bruxism). In clinical practice, we recommend the use of this grouping of symptoms and signs because it makes facilities the clinical study, definition of areas of dysfunction and diagnosis of the patient with RS.

The neural circuitry of visual artistic production and appreciation: A proposition.

PubMed

Chakravarty, Ambar

2012-04-01

The nondominant inferior parietal lobule is probably a major "store house" of artistic creativity. The ventromedial prefrontal lobe (VMPFL) is supposed to be involved in creative cognition and the dorsolateral prefrontal lobe (DLPFL) in creative output. The conceptual ventral and dorsal visual system pathways likely represent the inferior and superior longitudinal fasciculi. During artistic production, conceptualization is conceived in the VMPFL and the executive part is operated through the DLFPL. The latter transfers the concept to the visual brain through the superior longitudinal fasciculus (SLF), relaying on its path to the parietal cortex. The conceptualization at VMPFL is influenced by activity from the anterior temporal lobe through the uncinate fasciculus and limbic system pathways. The final visual image formed in the visual brain is subsequently transferred back to the DLPFL through the SLF and then handed over to the motor cortex for execution. During art appreciation, the image at the visual brain is transferred to the frontal lobe through the SLF and there it is matched with emotional and memory inputs from the anterior temporal lobe transmitted through the uncinate fasiculus. Beauty is perceived at the VMPFL and transferred through the uncinate fasciculus to the hippocampo-amygdaloid complex in the anterior temporal lobe. The limbic system (Papez circuit) is activated and emotion of appreciation is evoked. It is postulated that in practice the entire circuitry is activated simultaneously.

Tinnitus retraining therapy: a different view on tinnitus.

PubMed

Jastreboff, Pawel J; Jastreboff, Margaret M

2006-01-01

Tinnitus retraining therapy (TRT) is a method for treating tinnitus and decreased sound tolerance, based on the neurophysiological model of tinnitus. This model postulates involvement of the limbic and autonomic nervous systems in all cases of clinically significant tinnitus and points out the importance of both conscious and subconscious connections, which are governed by principles of conditioned reflexes. The treatments for tinnitus and misophonia are based on the concept of extinction of these reflexes, labeled as habituation. TRT aims at inducing changes in the mechanisms responsible for transferring signal (i.e., tinnitus, or external sound in the case of misophonia) from the auditory system to the limbic and autonomic nervous systems, and through this, remove signal-induced reactions without attempting to directly attenuate the tinnitus source or tinnitus/misophonia-evoked reactions. As such, TRT is effective for any type of tinnitus regardless of its etiology. TRT consists of: (1) counseling based on the neurophysiological model of tinnitus, and (2) sound therapy (with or without instrumentation). The main role of counseling is to reclassify tinnitus into the category of neutral stimuli. The role of sound therapy is to decrease the strength of the tinnitus signal. It is crucial to assess and treat tinnitus, decreased sound tolerance, and hearing loss simultaneously. Results from various groups have shown that TRT can be an effective method of treatment. Copyright (c) 2006 S. Karger AG, Basel.

The neural circuitry of visual artistic production and appreciation: A proposition

PubMed Central

Chakravarty, Ambar

2012-01-01

The nondominant inferior parietal lobule is probably a major “store house” of artistic creativity. The ventromedial prefrontal lobe (VMPFL) is supposed to be involved in creative cognition and the dorsolateral prefrontal lobe (DLPFL) in creative output. The conceptual ventral and dorsal visual system pathways likely represent the inferior and superior longitudinal fasciculi. During artistic production, conceptualization is conceived in the VMPFL and the executive part is operated through the DLFPL. The latter transfers the concept to the visual brain through the superior longitudinal fasciculus (SLF), relaying on its path to the parietal cortex. The conceptualization at VMPFL is influenced by activity from the anterior temporal lobe through the uncinate fasciculus and limbic system pathways. The final visual image formed in the visual brain is subsequently transferred back to the DLPFL through the SLF and then handed over to the motor cortex for execution. During art appreciation, the image at the visual brain is transferred to the frontal lobe through the SLF and there it is matched with emotional and memory inputs from the anterior temporal lobe transmitted through the uncinate fasiculus. Beauty is perceived at the VMPFL and transferred through the uncinate fasciculus to the hippocampo–amygdaloid complex in the anterior temporal lobe. The limbic system (Papez circuit) is activated and emotion of appreciation is evoked. It is postulated that in practice the entire circuitry is activated simultaneously. PMID:22566716

Responses of the extrapyramidal and limbic substance P systems to ibogaine and cocaine treatments.

PubMed

Alburges, M E; Ramos, B P; Bush, L; Hanson, G R

2000-02-25

Ibogaine is an indolamine found in the West Africa shrub, Tabernanthe iboga, and has been proposed for the treatment of addiction to central nervous system (CNS) stimulants such as cocaine and amphetamine. The mechanism of ibogaine action and its suitability as a treatment for drug addiction still remains unclear. Since previous studies demonstrated differential effects of stimulants of abuse (amphetamines) on neuropeptide systems such as substance P, we examined the impact of ibogaine and cocaine on extrapyramidal (striatum and substantia nigra) and limbic (nucleus accumbens and frontal cortex) substance P-like immunoreactivity. Ibogaine and cocaine treatments altered substance P systems by increasing striatal and nigral substance P-like immunoreactivity concentration 12 h after the last drug treatment. However, substance P-like immunoreactivity content was not significantly increased in nucleus accumbens after treatment with either drug. The ibogaine- and cocaine-induced increases in substance P-like immunoreactivity in striatum and substantia nigra were blocked by coadministration of selective dopamine D(1) receptor antagonist (SCH 23390; R(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine hydrochloride) or dopamine D(2) receptor antagonist (eticlopride; S(-)-3-Chloro-5-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2- methoxy-benzamide hydrochloride). Most of the responses by substance P systems to ibogaine administration resembled those caused by cocaine, except in cortical tissue where multiple administration of cocaine, but not ibogaine increased substance P-like immunoreactivity. These data suggest that substance P systems may contribute to the effects of ibogaine and cocaine treatment.

An fMRI study of the brain responses of traumatized mothers to viewing their toddlers during separation and play

PubMed Central

Moser, Dominik A.; Wang, Zhishun; Marsh, Rachel; Hao, XueJun; Duan, Yunsuo; Yu, Shan; Gunter, Benjamin; Murphy, David; McCaw, Jaime; Kangarlu, Alayar; Willheim, Erica; Myers, Michael M.; Hofer, Myron A.; Peterson, Bradley S.

2012-01-01

This study tested whether mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) vs healthy controls (HC) would show greater limbic and less frontocortical activity when viewing young children during separation compared to quiet play. Mothers of 20 children (12–42 months) participated: 11 IPV-PTSD mothers and 9 HC with no PTSD. During fMRI, mothers watched epochs of play and separation from their own and unfamiliar children. The study focused on comparison of PTSD mothers vs HC viewing children in separation vs play, and viewing own vs unfamiliar children in separation. Both groups showed distinct patterns of brain activation in response to viewing children in separation vs play. PTSD mothers showed greater limbic and less frontocortical activity (BA10) than HC. PTSD mothers also reported feeling more stressed than HC when watching own and unfamiliar children during separation. Their self-reported stress was associated with greater limbic and less frontocortical activity. Both groups also showed distinct patterns of brain activation in response to viewing their own vs unfamiliar children during separation. PTSD mothers’ may not have access to frontocortical regulation of limbic response upon seeing own and unfamiliar children in separation. This converges with previously reported associations of maternal IPV-PTSD and atypical caregiving behavior following separation. PMID:22021653

Norepinephrine-gamma-aminobutyric acid (GABA) interaction in limbic stress circuits: effects of reboxetine on GABAergic neurons.

PubMed

Herman, James P; Renda, Andrew; Bodie, Bryan

2003-01-15

Reboxetine is a selective norepinephrine (NE) reuptake inhibitor that exerts significant antidepressant action. The current study assessed norepinephrine-gamma-aminobutyric acid (GABA)-ergic mechanisms in reboxetine action, examining glutamic acid decarboxylase (GAD) mRNA expression in limbic neurocircuits following reboxetine within the context of chronic stress. Male rats received 25 mg/kg reboxetine/day, p.o. Reboxetine and vehicle animals were exposed to 1 week of variable stress exposure or handling. Behavioral responses to stress (open field) were tested on day 7, and animals were killed on day 8 to assess neuroendocrine stress responses and limbic GAD65/67 mRNA regulation (in situ hybridization). Reboxetine significantly decreased behavioral reactivity in the open field. Reboxetine administration did not affect expression of GAD65/67 mRNA in handled rats; however, administration to stressed animals reduced GAD67 (but not GAD65) mRNA in the medial amygdaloid nucleus, posteromedial bed nucleus of the stria terminalis, and dentate gyrus. In contrast, GAD65 mRNA expression was increased by reboxetine in the lateral septum of stressed animals. Norepinephrine pathways appear to modulate synthesis of GABA in central limbic stress circuits. Decreases in GABA synthetic capacity suggest reduced activation of stress-excitatory pathways and enhanced activation of stress-inhibitory circuits, and is consistent with a role for GABA in the antidepressant efficacy of NE reuptake inhibitors.

The effects of lithium and anticonvulsants on brain structure in bipolar disorder.

PubMed

Germaná, C; Kempton, M J; Sarnicola, A; Christodoulou, T; Haldane, M; Hadjulis, M; Girardi, P; Tatarelli, R; Frangou, S

2010-12-01

To investigate the effect of lithium, anticonvulsants and antipsychotics on brain structure in bipolar disorder (BD). A cross-sectional structural brain magnetic resonance imaging study of 74 remitted patients with BD, aged 18-65, who were receiving long-term prophylactic treatment with lithium or anticonvulsants or antipsychotics. Global and regional grey matter, white matter, and cerebrospinal fluid volumes were compared between treatment groups. Grey matter in the subgenual anterior cingulate gyrus on the right (extending into the hypothalamus) and in the postcentral gyrus, the hippocampus/amygdale complex and the insula on the left was greater in BD patients on lithium treatment compared to all other treatment groups. Lithium treatment in BD has a significant effect on brain structure particularly in limbic/paralimbic regions associated with emotional processing. © 2010 John Wiley & Sons A/S.

Can understanding the neurobiology of body dysmorphic disorder (BDD) inform treatment?

PubMed

Rossell, Susan L; Harrison, Ben J; Castle, David

2015-08-01

We aim to provide a clinically focused review of the neurobiological literature in body dysmorphic disorder (BDD), with a focus on structural and functional neuroimaging. There has been a recent influx of studies examining the underlying neurobiology of BDD using structural and functional neuroimaging methods. Despite obvious symptom similarities with obsessive-compulsive disorder (OCD), no study to date has directly compared the two groups using neuroimaging techniques. Studies have established that there are limbic and visual cortex abnormalities in BDD, in contrast to fronto-striatal differences in OCD. Such data suggests affect or visual training maybe useful in BDD. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Effect of Long-Term Sodium Salicylate Administration on Learning, Memory, and Neurogenesis in the Rat Hippocampus

PubMed Central

Niu, Haichen; Ding, Sheng; Li, Haiying; Wei, Jianfeng; Ren, Chao; Wu, Xiujuan

2018-01-01

Tinnitus is thought to be caused by damage to the auditory and nonauditory system due to exposure to loud noise, aging, or other etiologies. However, at present, the exact neurophysiological basis of chronic tinnitus remains unknown. To explore whether the function of the limbic system is disturbed in tinnitus, the hippocampus was selected, which plays a vital role in learning and memory. The hippocampal function was examined with a learning and memory procedure. For this purpose, sodium salicylate (NaSal) was used to create a rat animal model of tinnitus, evaluated with prepulse inhibition behavior (PPI). The acquisition and retrieval abilities of spatial memory were measured using the Morris water maze (MWM) in NaSal-treated and control animals, followed by observation of c-Fos and delta-FosB protein expression in the hippocampal field by immunohistochemistry. To further identify the neural substrate for memory change in tinnitus, neurogenesis in the subgranular zone of the dentate gyrus (DG) was compared between the NaSal group and the control group. The results showed that acquisition and retrieval of spatial memory were impaired by NaSal treatment. The expression of c-Fos and delta-FosB protein was also inhibited in NaSal-treated animals. Simultaneously, neurogenesis in the DG was also impaired in tinnitus animals. In general, our data suggest that the hippocampal system (limbic system) may play a key role in tinnitus pathology.

Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volkow, N.D.; Wang, G.; Volkow, N.D.

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and {sup 18}FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo andmore » once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction.« less

Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Tomasi, Dardo; Telang, Frank; Fowler, Joanna S.; Pradhan, Kith; Jayne, Millard; Logan, Jean; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher

2010-01-01

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2–5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction. PMID:20634975

Cocaine cue-induced dopamine release in amygdala and hippocampus: a high-resolution PET [¹⁸F]fallypride study in cocaine dependent participants.

PubMed

Fotros, Aryandokht; Casey, Kevin F; Larcher, Kevin; Verhaeghe, Jeroen A J; Cox, Sylvia M L; Gravel, Paul; Reader, Andrew J; Dagher, Alain; Benkelfat, Chawki; Leyton, Marco

2013-08-01

Drug-related cues are potent triggers for relapse in people with cocaine dependence. Dopamine (DA) release within a limbic network of striatum, amygdala and hippocampus has been implicated in animal studies, but in humans it has only been possible to measure effects in the striatum. The objective here was to measure drug cue-induced DA release in the amygdala and hippocampus using high-resolution PET with [(18)F]fallypride. Twelve cocaine-dependent volunteers (mean age: 39.6 ± 8.0 years; years of cocaine use: 15.9 ± 7.4) underwent two [(18)F]fallypride high-resolution research tomography-PET scans, one with exposure to neutral cues and one with cocaine cues. [(18)F]Fallypride non-displaceable-binding potential (BPND) values were derived for five regions of interest (ROI; amygdala, hippocampus, ventral limbic striatum, associative striatum, and sensorimotor striatum). Subjective responses to the cues were measured with visual analog scales and grouped using principal component analysis. Drug cue exposure significantly decreased BPND values in all five ROI in subjects who had a high-, but not low-, craving response (limbic striatum: p=0.019, associative striatum: p=0.008, sensorimotor striatum: p=0.004, amygdala: p=0.040, and right hippocampus: p=0.025). Individual differences in the cue-induced craving response predicted the magnitude of [(18)F]fallypride responses within the striatum (ventral limbic: r=0.581, p=0.048; associative: r=0.589, p=0.044; sensorimotor: r=0.675, p=0.016). To our knowledge this study provides the first evidence of drug cue-induced DA release in the amygdala and hippocampus in humans. The preferential induction of DA release among high-craving responders suggests that these aspects of the limbic reward network might contribute to drug-seeking behavior.

Functional mapping of the primate auditory system.

PubMed

Poremba, Amy; Saunders, Richard C; Crane, Alison M; Cook, Michelle; Sokoloff, Louis; Mishkin, Mortimer

2003-01-24

Cerebral auditory areas were delineated in the awake, passively listening, rhesus monkey by comparing the rates of glucose utilization in an intact hemisphere and in an acoustically isolated contralateral hemisphere of the same animal. The auditory system defined in this way occupied large portions of cerebral tissue, an extent probably second only to that of the visual system. Cortically, the activated areas included the entire superior temporal gyrus and large portions of the parietal, prefrontal, and limbic lobes. Several auditory areas overlapped with previously identified visual areas, suggesting that the auditory system, like the visual system, contains separate pathways for processing stimulus quality, location, and motion.

Nicotine increases brain functional network efficiency.

PubMed

Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Laura F; Tregellas, Jason R

2012-10-15

Despite the use of cholinergic therapies in Alzheimer's disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network's tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer's disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. Published by Elsevier Inc.

Nicotine Increases Brain Functional Network Efficiency

PubMed Central

Wylie, Korey P.; Rojas, Donald C.; Tanabe, Jody; Martin, Laura F.; Tregellas, Jason R.

2012-01-01

Despite the use of cholinergic therapies in Alzheimer’s disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting-state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network’s tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer’s disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. PMID:22796985

Glutamatergic transmission in the nucleus of the solitary tract modulates memory through influences on amygdala noradrenergic systems.

PubMed

Miyashita, Teiko; Williams, Cedric L

2002-02-01

The authors examined whether glutamate release from the vagus nerve onto the nucleus of the solitary tract (NTS) is one mechanism by which the vagus influences memory and neural activity in limbic structures. Rats trained to drink from a spout were given a footshock (0.35 mA) on Day 5 after approaching the spout. Phosphate-buffered saline or 5.0, 50.0, or 100.0 nmol/0.5 microl glutamate was then infused into the NTS. Glutamate (5.0 or 50.0 nmol) significantly enhanced memory on the retention test. In Experiment 2, this effect was attenuated by blocking noradrenergic receptors in the amygdala with propranolol (0.3 microg/0.5 microl). Experiment 3 used in vivo microdialysis to determine whether footshock plus glutamate (50.0 nmol) alters noradrenergic output in the amygdala. These treatments caused a significant and long-lasting increase in amygdala noradrenergic concentrations. The results indicate that glutamate may be one transmitter that conveys the effects of vagal activation on brain systems that process memory.

Testosterone in the brain: neuroimaging findings and the potential role for neuropsychopharmacology.

PubMed

Höfer, Peter; Lanzenberger, Rupert; Kasper, Siegfried

2013-02-01

Testosterone plays a substantial role in a number of physiological processes in the brain. It is able to modulate the expression of certain genes by binding to androgen receptors. Acting via neurotransmitter receptors, testosterone shows the potential to mediate a non-genomic so-called "neuroactive effect". Various neurotransmitter systems are also influenced by the aromatized form of testosterone, estradiol. The following article summarizes the findings of preclinical and clinical neuroimaging studies including structural and functional magnetic resonance imaging (MRI/fMRI), voxel based morphometry (VBM), as well as pharmacological fMRI (phfMRI) and positron emission tomography (PET) regarding the effects of testosterone on the human brain. The impact of testosterone on the pathogenesis of psychiatric disorders and on sex-related prevalence differences have been supported by a wide range of clinical studies. An antidepressant effect of testosterone can be implicitly explained by its effects on the limbic system--especially amygdala, a major target in the treatment of depression--solidly demonstrated by a large body of neuroimaging findings. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

Chronic anosmia induces depressive behavior and reduced anxiety via dysregulation of glucocorticoid receptor and corticotropin-releasing hormone in a mouse model.

PubMed

Ahn, Sangzin; Shin, Hyun-Woo; Mahmood, Usman; Khalmuratova, Roza; Jeon, Sea-Yuong; Jin, Hong Ryul; Choi, Jung-Seok; Kim, Hye-Sun; Kim, Dae Woo

2016-03-01

Olfactory loss is highly prevalent, and comorbid mood disorders are common. Considering olfactory input is highly interconnected with the limbic system, and that the limbic system manages mood, it is predictable that impairments in the sense of smell may result in mood changes. Chronic olfactory deficits were induced by repeated intranasal irrigation of ZnSO4 for 12 weeks in BALB/c mice. H&E staining, OMP staining, and potato chip finding test were performed to confirm olfactory loss. Tail suspension, forced swim, and splash tests were performed to evaluate depression, as well as open field, elevated plus maze tests were applied to assess anxiety. The mRNA levels of glucocorticoid receptor (GR) and corticotropin releasing hormone (CRH) were measured by real-time PCR to confirm relevant molecular changes. Disruption of the olfactory epithelium and olfactory loss was confirmed in histological studies and potato chip finding test. Behavioral tests show that the chronic anosmic state caused increased depression and reduced anxiety. PCR data showed that mRNA levels of GR in the hypothalamus and CRH in the amygdala were significantly decreased. These results propose that ZnSO4-induced chronic anosmia can cause a depressive and anxiolytic state via decreased hypothalamic GR and amygdalar CRH.

The neural correlates of priming emotion and reward systems for conflict processing in alcoholics.

PubMed

Schulte, T; Jung, Y-C; Sullivan, E V; Pfefferbaum, A; Serventi, M; Müller-Oehring, E M

2017-12-01

Emotional dysregulation in alcoholism (ALC) may result from disturbed inhibitory mechanisms. We therefore tested emotion and alcohol cue reactivity and inhibitory processes using negative priming. To test the neural correlates of cue reactivity and negative priming, 26 ALC and 26 age-matched controls underwent functional MRI performing a Stroop color match-to-sample task. In cue reactivity trials, task-irrelevant emotion and alcohol-related pictures were interspersed between color samples and color words. In negative priming trials, pictures primed the semantic content of an alcohol or emotion Stroop word. Behaviorally, both groups showed response facilitation to picture cue trials and response inhibition to primed trials. For cue reactivity to emotion and alcohol pictures, ALC showed midbrain-limbic activation. By contrast, controls activated frontoparietal executive control regions. Greater midbrain-hippocampal activation in ALC correlated with higher amounts of lifetime alcohol consumption and higher anxiety. With negative priming, ALC exhibited frontal cortical but not midbrain-hippocampal activation, similar to the pattern observed in controls. Higher frontal activation to alcohol-priming correlated with less craving and to emotion-priming with fewer depressive symptoms. The findings suggest that neurofunctional systems in ALC can be primed to deal with upcoming emotion- and alcohol-related conflict and can overcome the prepotent midbrain-limbic cue reactivity response.

Anti Ma2-associated myeloradiculopathy: expanding the phenotype of anti-Ma2 associated paraneoplastic syndromes

PubMed Central

Murphy, Sinead M; Khan, Usman; Alifrangis, Constantine; Hazell, Steven; Hrouda, David; Blake, Julian; Ball, Joanna; Gabriel, Carolyn; Markarian, Pierre; Rees, Jeremy; Karim, Abid; Seckl, Michael J; Lunn, Michael P; Reilly, Mary M

2013-01-01

Anti-Ma2 associated paraneoplastic syndrome usually presents as limbic encephalitis in association with testicular tumours.1, 2 Only four patients have been reported with involvement outside the CNS, two of whom also had limbic or brainstem encephalitis.2, 3 We report a man with anti- Ma2 associated myeloradiculopathy and previous testicular cancer whose neurological syndrome stabilised and anti-Ma2 titres fell following orchidectomy of a microscopically normal testis. PMID:21205983

Limbic and Basal Ganglia Neuroanatomical Correlates of Gait and Executive Function: Older Adults With Mild Cognitive Impairment and Intact Cognition.

PubMed

McGough, Ellen L; Kelly, Valerie E; Weaver, Kurt E; Logsdon, Rebecca G; McCurry, Susan M; Pike, Kenneth C; Grabowski, Thomas J; Teri, Linda

2018-04-01

This study aimed to examine differences in spatiotemporal gait parameters between older adults with amnestic mild cognitive impairment and normal cognition and to examine limbic and basal ganglia neural correlates of gait and executive function in older adults without dementia. This was a cross-sectional study of 46 community-dwelling older adults, ages 70-95 yrs, with amnestic mild cognitive impairment (n = 23) and normal cognition (n = 23). Structural magnetic resonance imaging was used to attain volumetric measures of limbic and basal ganglia structures. Quantitative motion analysis was used to measure spatiotemporal parameters of gait. The Trail Making Test was used to assess executive function. During fast-paced walking, older adults with amnestic mild cognitive impairment demonstrated significantly slower gait speed and shorter stride length compared with older adults with normal cognition. Stride length was positively correlated with hippocampal, anterior cingulate, and nucleus accumbens volumes (P < 0.05). Executive function was positively correlated with hippocampal, anterior cingulate, and posterior cingulate volumes (P < 0.05). Compared with older adults with normal cognition, those with amnestic mild cognitive impairment demonstrated slower gait speed and shorter stride length, during fast-paced walking, and lower executive function. Hippocampal and anterior cingulate volumes demonstrated moderate positive correlation with both gait and executive function, after adjusting for age. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) discuss gait performance and cognitive function in older adults with amnestic mild cognitive impairment versus normal cognition, (2) discuss neurocorrelates of gait and executive function in older adults without dementia, and (3) recognize the importance of assessing gait speed and cognitive function in the clinical management of older adults at risk for dementia. Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Emotions and hemispheric specialization.

PubMed

Kyle, N L

1988-09-01

Studies of lateralization and specialization of brain function have increased our understanding of emotional processes in the brain. It has been said that the way in which we understand the emotional interrelatedness of brain layers and segments may have important effects on human society. Earlier studies of brain function, especially of limbic effects, suggested a dichotomous state of affairs between the phylogenetically older brain and the newer cortical areas--between affect and cognition. Such concepts are considered here in the light of specialization studies. From the beginning hemispheric laterality research has implicated emotionality and emotional pathology. It also appears that some limbic functions may be mediated in a lateralized fashion. Neuropsychologists have directed much work toward localization of function from its earliest stage; since the 1960s an emphasis has been on "mapping" of cortical functions in terms of psychopathologic disabilities. Various disability groups have been studied in this way, and it may be concluded that neuropsychologic measures are sensitive to changes in cerebral functioning and may have effective lateralizing and localizing ability under specified conditions. Studies of limbic effects in the brain emphasize their importance in emotional behavior but also their interrelatedness with other structures, for example, the frontal and temporal lobes, and particularly the right hemisphere. Studies of commissurotomy (split-brain) patients tend to bear out these relationships. In split-brain subjects the marked reduction in affective verbal and nonverbal behavior reflects the interruption of transcallosal impulses that normally permit emotional infusion of cortical structures to take place. These effects include verbal, visual, and auditory patterns that mediate the ability to decode complex nonverbal patterns and may result in a reduction of "inner speech," that is, symbollexia. They may further lead to a condition of "functional commissurotomy" in psychiatric patients with presumably intact brains. It would also appear that lateralization may be variable in terms of inhibitory and facilitative effects; emotional factors may play a part in this variability in some clinical cases in which functional or reactive features predominate, for example, in alexithymia. Ideas of hemispheric specialization have been extended to other areas of individual and social behavior. Creative ability has been understood by some authors to be a product of the relatively dynamic relationships existing between specialized areas of the brain.(ABSTRACT TRUNCATED AT 400 WORDS)

Neurobiology of Wisdom?: A Literature Overview

PubMed Central

Meeks, Thomas W.; Jeste, Dilip V.

2013-01-01

Context Wisdom is a unique psychological trait noted since antiquity, long discussed in humanities disciplines, recently operationalized by psychology and sociology researchers, but largely unexamined in psychiatry or biology. Objective We discuss recent neurobiological studies related to subcomponents of wisdom identified from several published definitions/descriptions of wisdom by clinical investigators in the field – i.e., prosocial attitudes/behaviors, social decision-making/pragmatic knowledge of life, emotional homeostasis, reflection/self-understanding, value relativism/tolerance, and acknowledgement of and dealing effectively with uncertainty. Design Literature overview focusing primarily on neuroimaging/brain localization and secondarily on neurotransmitters, including their genetic determinants. Results Functional neuroimaging permits exploration of neural correlates of complex psychological attributes such as those proposed to comprise wisdom. The prefrontal cortex figures prominently in several wisdom subcomponents (e.g., emotional regulation, decision-making, value relativism), primarily via top-down regulation of limbic and striatal regions. The lateral prefrontal cortex facilitates calculated, reason-based decision-making, whereas the medial prefrontal cortex is implicated in emotional valence and prosocial attitudes/behaviors. Reward neurocircuitry (ventral striatum, nucleus accumbens) also appears important for promoting prosocial attitudes/behaviors. Monoaminergic activity (especially dopaminergic and serotonergic), influenced by several genetic polymorphisms, is critical to certain subcomponents of wisdom such as emotional regulation (including impulse control), decision-making, and prosocial behaviors. Conclusions We have proposed a speculative model of the neurobiology of wisdom involving fronto-striatal and fronto-limbic circuits and monoaminergic pathways. Wisdom may involve optimal balance between functions of phylogenetically more primitive brain regions (limbic system) and newer ones (prefrontal cortex). Limitations of the putative model are stressed. It is hoped that this review will stimulate further research in characterization, assessment, neurobiology, and interventions related to wisdom. PMID:19349305

Muscarinic receptor binding increases in anterior thalamus and cingulate cortex during discriminative avoidance learning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vogt, B.A.; Gabriel, M.; Vogt, L.J.

Training-induced neuronal activity develops in the mammalian limbic system during discriminative avoidance conditioning. This study explores behaviorally relevant changes in muscarinic ACh receptor binding in 52 rabbits that were trained to one of five stages of conditioned response acquisition. Sixteen naive and 10 animals yoked to criterion performance served as control cases. Upon reaching a particular stage of training, the brains were removed and autoradiographically assayed for 3H-oxotremorine-M binding with 50 nM pirenzepine (OxO-M/PZ) or for 3H-pirenzepine binding in nine limbic thalamic nuclei and cingulate cortex. Specific OxO-M/PZ binding increased in the parvocellular division of the anterodorsal nucleus early inmore » training when the animals were first exposed to pairing of the conditional and unconditional stimuli. Elevated binding in this nucleus was maintained throughout subsequent training. In the parvocellular division of the anteroventral nucleus (AVp), OxO-M/PZ binding progressively increased throughout training, reached a peak at the criterion stage of performance, and returned to control values during extinction sessions. Peak OxO-M/PZ binding in AVp was significantly elevated over that for cases yoked to criterion performance. In the magnocellular division of the anteroventral nucleus (AVm), OxO-M/PZ binding was elevated only during criterion performance of the task, and it was unaltered in any other limbic thalamic nuclei. Specific OxO-M/PZ binding was also elevated in most layers in rostral area 29c when subjects first performed a significant behavioral discrimination. Training-induced alterations in OxO-M/PZ binding in AVp and layer Ia of area 29c were similar and highly correlated.« less

Dissociable Behavioral, Physiological and Neural Effects of Acute Glucose and Fructose Ingestion: A Pilot Study

PubMed Central

Schmidt, André; Zimak, Nina; Peterli, Ralph; Beglinger, Christoph; Borgwardt, Stefan

2015-01-01

Previous research has revealed that glucose and fructose ingestion differentially modulate release of satiation hormones. Recent studies have begun to elucidate brain-gut interactions with neuroimaging approaches such as magnetic resonance imaging (MRI), but the neural mechanism underlying different behavioral and physiological effects of glucose and fructose are unclear. In this paper, we have used resting state functional MRI to explore whether acute glucose and fructose ingestion also induced dissociable effects in the neural system. Using a cross-over, double-blind, placebo-controlled design, we compared resting state functional connectivity (rsFC) strengths within the basal ganglia/limbic network in 12 healthy lean males. Each subject was administered fructose, glucose and placebo on three separate occasions. Subsequent correlation analysis was used to examine relations between rsFC findings and plasma concentrations of satiation hormones and subjective feelings of appetite. Glucose ingestion induced significantly greater elevations in plasma glucose, insulin, GLP-1 and GIP, while feelings of fullness increased and prospective food consumption decreased relative to fructose. Furthermore, glucose increased rsFC of the left caudatus and putamen, precuneus and lingual gyrus more than fructose, whereas within the basal ganglia/limbic network, fructose increased rsFC of the left amygdala, left hippocampus, right parahippocampus, orbitofrontal cortex and precentral gyrus more than glucose. Moreover, compared to fructose, the increased rsFC after glucose positively correlated with the glucose-induced increase in insulin. Our findings suggest that glucose and fructose induce dissociable effects on rsFC within the basal ganglia/limbic network, which are probably mediated by different insulin levels. A larger study would be recommended in order to confirm these findings. PMID:26107810

Maternal Neural Responses to Infant Cries and Faces: Relationships with Substance Use

PubMed Central

Landi, Nicole; Montoya, Jessica; Kober, Hedy; Rutherford, Helena J. V.; Mencl, W. Einar; Worhunsky, Patrick D.; Potenza, Marc N.; Mayes, Linda C.

2011-01-01

Substance abuse in pregnant and recently post-partum women is a major public health concern because of effects on the infant and on the ability of the adult to care for the infant. In addition to the negative health effects of teratogenic substances on fetal development, substance use can contribute to difficulties associated with the social and behavioral aspects of parenting. Neural circuits associated with parenting behavior overlap with circuits involved in addiction (e.g., frontal, striatal, and limbic systems) and thus may be co-opted for the craving/reward cycle associated with substance use and abuse and be less available for parenting. The current study investigates the degree to which neural circuits associated with parenting are disrupted in mothers who are substance-using. Specifically, we used functional magnetic resonance imaging to examine the neural response to emotional infant cues (faces and cries) in substance-using compared to non-using mothers. In response to both faces (of varying emotional valence) and cries (of varying distress levels), substance-using mothers evidenced reduced neural activation in regions that have been previously implicated in reward and motivation as well as regions involved in cognitive control. Specifically, in response to faces, substance users showed reduced activation in prefrontal regions, including the dorsolateral and ventromedial prefrontal cortices, as well as visual processing (occipital lobes) and limbic regions (parahippocampus and amygdala). Similarly, in response to infant cries, substance-using mothers showed reduced activation relative to non-using mothers in prefrontal regions, auditory sensory processing regions, insula and limbic regions (parahippocampus and amygdala). These findings suggest that infant stimuli may be less salient for substance-using mothers, and such reduced saliency may impair developing infant-caregiver attachment and the ability of mothers to respond appropriately to their infants. PMID:21720537

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens.

PubMed

Ross, Erika K; Kim, Joo Pyung; Settell, Megan L; Han, Seong Rok; Blaha, Charles D; Min, Hoon-Ki; Lee, Kendall H

2016-03-01

Deep brain stimulation (DBS) is a circuit-based treatment shown to relieve symptoms from multiple neurologic and neuropsychiatric disorders. In order to treat the memory deficit associated with Alzheimer's disease (AD), several clinical trials have tested the efficacy of DBS near the fornix. Early results from these studies indicated that patients who received fornix DBS experienced an improvement in memory and quality of life, yet the mechanisms behind this effect remain controversial. It is known that transmission between the medial limbic and corticolimbic circuits plays an integral role in declarative memory, and dysfunction at the circuit level results in various forms of dementia, including AD. Here, we aimed to determine the potential underlying mechanism of fornix DBS by examining the functional circuitry and brain structures engaged by fornix DBS. A multimodal approach was employed to examine global and local temporal changes that occur in an anesthetized swine model of fornix DBS. Changes in global functional activity were measured by functional MRI (fMRI), and local neurochemical changes were monitored by fast scan cyclic voltammetry (FSCV) during electrical stimulation of the fornix. Additionally, intracranial microinfusions into the nucleus accumbens (NAc) were performed to investigate the global activity changes that occur with dopamine and glutamate receptor-specific antagonism. Hemodynamic responses in both medial limbic and corticolimbic circuits measured by fMRI were induced by fornix DBS. Additionally, fornix DBS resulted in increases in dopamine oxidation current (corresponding to dopamine efflux) monitored by FSCV in the NAc. Finally, fornix DBS-evoked hemodynamic responses in the amygdala and hippocampus decreased following dopamine and glutamate receptor antagonism in the NAc. The present findings suggest that fornix DBS modulates dopamine release on presynaptic dopaminergic terminals in the NAc, involving excitatory glutamatergic input, and that the medial limbic and corticolimbic circuits interact in a functional loop. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain and spinal cord metabolic activity during propofol anaesthesia.

PubMed

Cavazzuti, M; Porro, C A; Barbieri, A; Galetti, A

1991-04-01

We have investigated the effects of propofol anaesthesia on the metabolic activity pattern of 35 regions of the rat brain and cervical spinal cord using the 14C-2-deoxyglucose technique. Anaesthesia was produced by an i.v. bolus of the commercial preparation of the drug (8 mg kg-1) and maintained with successive bolus administrations of 6 mg kg-1. Functional activity values (expressed as rates of local utilization of glucose) were reduced in 31 grey matter and two white matter structures in a propofol group relative both to saline-injected and vehicle-injected (aqueous emulsion containing 10% soya bean oil, 1.2% egg phosphatide and 2.25% glycerol) controls. Values from the two control groups did not differ significantly. Propofol-induced depression of metabolic activity was present in central nervous system regions belonging to sensory (auditory, visual and somatosensory), motor and limbic systems, including spinal cord grey matter. Mean percentage decreases ranged from 40% (vestibular nuclei) to 76% (cingulate cortex). Although these values may be slightly overestimated because of the modest increase in PaCo2 in the anaesthetized group, propofol appeared to elicit generalized reduction of central nervous system functional activity.

LORETA functional imaging in antipsychotic-naive and olanzapine-, clozapine- and risperidone-treated patients with schizophrenia.

PubMed

Tislerova, Barbora; Brunovsky, Martin; Horacek, Jiri; Novak, Tomas; Kopecek, Miloslav; Mohr, Pavel; Krajca, Vladimír

2008-01-01

The aim of our study was to detect changes in the distribution of electrical brain activity in schizophrenic patients who were antipsychotic naive and those who received treatment with clozapine, olanzapine or risperidone. We included 41 subjects with schizophrenia (antipsychotic naive = 11; clozapine = 8; olanzapine = 10; risperidone = 12) and 20 healthy controls. Low-resolution brain electromagnetic tomography was computed from 19-channel electroencephalography for the frequency bands delta, theta, alpha-1, alpha-2, beta-1, beta-2 and beta-3. We compared antipsychotic-naive subjects with healthy controls and medicated patients. (1) Comparing antipsychotic-naive subjects and controls we found a general increase in the slow delta and theta frequencies over the fronto-temporo-occipital cortex, particularly in the temporolimbic structures, an increase in alpha-1 and alpha-2 in the temporal cortex and an increase in beta-1 and beta-2 in the temporo-occipital and posterior limbic structures. (2) Comparing patients who received clozapine and those who were antipsychotic naive, we found an increase in delta and theta frequencies in the anterior cingulate and medial frontal cortex, and a decrease in alpha-1 and beta-2 in the occipital structures. (3) Comparing patients taking olanzapine with those who were antipsychotic naive, there was an increase in theta frequencies in the anterior cingulum, a decrease in alpha-1, beta-2 and beta-3 in the occipital cortex and posterior limbic structures, and a decrease in beta-3 in the frontotemporal cortex and anterior cingulum. (4) In patients taking risperidone, we found no significant changes from those who were antipsychotic naive. Our results in antipsychotic-naive patients are in agreement with existing functional findings. Changes in those taking clozapine and olanzapine versus those who were antipsychotic naive suggest a compensatory mechanism in the neurobiological substrate for schizophrenia. The lack of difference in risperidone patients versus antipsychotic-naive subjects may relate to risperidone's different pharmacodynamic mechanism. Copyright 2008 S. Karger AG, Basel.

Motivational Modulation of Rhythms of the Expression of the Clock Protein PER2 in the Limbic Forebrain.

PubMed

Amir, Shimon; Stewart, Jane

2009-05-15

Key molecular components of the mammalian circadian clock are expressed rhythmically in many brain areas and peripheral tissues in mammals. Here we review findings from our work on rhythms of expression of the clock protein Period2 (PER2) in four regions of the limbic forebrain known to be important in the regulation of motivational and emotional states. These regions include the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), the central nucleus of the amygdala (CEA), the basolateral amygdala (BLA), and the dentate gyrus (DG). Daily rhythms in the expression of PER2 in these regions are controlled by the master circadian pacemaker, the suprachiasmatic nucleus (SCN), but, importantly, they are also sensitive to homeostatic perturbations and to hormonal states that directly influence motivated behavior. Thus, circadian information from the SCN and homeostatic signals are integrated in these regions of the limbic forebrain to affect the temporal organization of motivational and emotional processes.

Diurnal cortisol amplitude and fronto-limbic activity in response to stressful stimuli

PubMed Central

Cunningham-Bussel, Amy C.; Root, James C.; Butler, Tracy; Tuescher, Oliver; Pan, Hong; Epstein, Jane; Weisholtz, Daniel S.; Pavony, Michelle; Silverman, Michael E.; Goldstein, Martin S.; Altemus, Margaret; Cloitre, Marylene; LeDoux, Joseph; McEwen, Bruce; Stern, Emily; Silbersweig, David

2014-01-01

Summary The development and exacerbation of many psychiatric and neurologic conditions are associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis as measured by aberrant levels of cortisol secretion. Here we report on the relationship between the amplitude of diurnal cortisol secretion, measured across 3 typical days in 18 healthy individuals, and blood oxygen level dependant (BOLD) response in limbic fear/stress circuits, elicited by in-scanner presentation of emotionally negative stimuli, specifically, images of the World Trade Center (WTC) attack. Results indicate that subjects who secrete a greater amplitude of cortisol diurnally demonstrate less brain activation in limbic regions, including the amygdala and hippocampus/parahippocampus, and hypothalamus during exposure to traumatic WTC-related images. Such initial findings can begin to link our understanding, in humans, of the relationship between the diurnal amplitude of a hormone integral to the stress response, and those neuroanatomical regions that are implicated as both modulating and being modulated by that response. PMID:19135805

Dysregulation of prefrontal cortex-mediated slow evolving limbic dynamics drives stress-induced emotional pathology

PubMed Central

Hultman, Rainbo; Mague, Stephen D.; Li, Qiang; Katz, Brittany M.; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K.; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D.; Dzirasa, Kafui

2016-01-01

Summary Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social-defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. PMID:27346529

Common limbic and frontal-striatal disturbances in patients with obsessive compulsive disorder, panic disorder and hypochondriasis.

PubMed

van den Heuvel, O A; Mataix-Cols, D; Zwitser, G; Cath, D C; van der Werf, Y D; Groenewegen, H J; van Balkom, A J L M; Veltman, D J

2011-11-01

Direct comparisons of brain function between obsessive compulsive disorder (OCD) and other anxiety or OCD spectrum disorders are rare. This study aimed to investigate the specificity of altered frontal-striatal and limbic activations during planning in OCD, a prototypical anxiety disorder (panic disorder) and a putative OCD spectrum disorder (hypochondriasis). The Tower of London task, a 'frontal-striatal' task, was used during functional magnetic resonance imaging measurements in 50 unmedicated patients, diagnosed with OCD (n=22), panic disorder (n=14) or hypochondriasis (n=14), and in 22 healthy subjects. Blood oxygen level-dependent (BOLD) signal changes were calculated for contrasts of interest (planning versus baseline and task load effects). Moreover, correlations between BOLD responses and both task performance and state anxiety were analysed. Overall, patients showed a decreased recruitment of the precuneus, caudate nucleus, globus pallidus and thalamus, compared with healthy controls. There were no statistically significant differences in brain activation between the three patient groups. State anxiety was negatively correlated with dorsal frontal-striatal activation. Task performance was positively correlated with dorsal frontal-striatal recruitment and negatively correlated with limbic and ventral frontal-striatal recruitment. Multiple regression models showed that adequate task performance was best explained by independent contributions from dorsolateral prefrontal cortex (positive correlation) and amygdala (negative correlation), even after controlling for state anxiety. Patients with OCD, panic disorder and hypochondriasis share similar alterations in frontal-striatal brain regions during a planning task, presumably partly related to increased limbic activation.

Limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies as a cause of adult-onset mesial temporal lobe epilepsy.

PubMed

Toyota, Tomoko; Akamatsu, Naoki; Tsuji, Sadatoshi; Nishizawa, Shigeru

2014-06-01

Recently, some reports have indicated that limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies (VGKC-Ab) is a cause of adult-onset mesial temporal lobe epilepsy (MTLE). We report a 53-year-old woman who had her first epileptic seizure at the age of 50 years old. Examination by 3-Tesla brain MRI revealed left hippocampal high signal intensity and swelling on fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging at 2 months after her first seizure. The patient received intravenous methylprednisolone and carbamazepine 300 mg/day. One month later, MRI revealed improvement of her left hippocampal abnormalities. Thereafter, she had no seizures, however, three years after her first seizure, EEG revealed a seizure pattern in the left temporal region. Brain MRI revealed left hippocampal high signal intensity and brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism. Her serum VGKC-Ab levels were 118 pM(normal < 100 pM). Intravenous methylprednisolone therapy was reinitiated. Two months later, her hippocampal abnormalities had improved and 3 months later her VGKC-Ab levels decreased to 4.4 pM. Remission of the epileptic seizures was also observed. This MTLE in the middle age was considered as limbic encephalitis associated with anti- VGKC-Ab. In cases of unexplained adult-onset MTLE, limbic encephalitis associated with anti-VGKC-Ab, which responds well to immunotherapy, should be considered in the differential diagnosis.

Impaired modulation of attention and emotion in schizophrenia.

PubMed

Dichter, Gabriel S; Bellion, Carolyn; Casp, Michael; Belger, Aysenil

2010-05-01

Fronto-limbic interactions facilitate the generation of task-relevant responses while inhibiting interference from emotionally distracting information. Schizophrenia is associated with deficits in both executive attention and affective regulation. This study aims to elucidate the neural correlates of emotion-attention regulation and shifting in schizophrenia. We employed functional magnetic resonance imaging to probe the fronto-limbic regions in 16 adults with schizophrenia and 13 matched adults with no history of psychiatric illness. Subjects performed a forced-choice visual oddball task where they detected infrequent target circles embedded in a series of infrequent nontarget aversive and neutral pictures and frequent squares. In control participants, target events activated a dorsal frontoparietal network, whereas these regions were deactivated by aversive stimuli. Conversely, ventral frontolimbic brain regions were activated by aversive stimuli and deactivated by target events. In the patient group, regional hemodynamic timecourses revealed not only reduced activation to target and aversive events in dorsal executive and ventral limbic regions, respectively, but also reduced deactivation to target and aversive stimuli in ventral and dorsal regions, respectively, relative to the control group. Patients further showed reduced spatial extent of activation in the right inferior frontal gyrus during the target and aversive conditions. Activation of the anterior cingulate to aversive images was inversely related to severity of avolition and anhedonia symptoms in the schizophrenia group. These results suggest both frontal and limbic dysfunction in schizophrenia as well as aberrant reciprocal inhibitions between these regions during attention-emotion modulation in this disorder.

Limbic-Auditory Interactions of Tinnitus: An Evaluation Using Diffusion Tensor Imaging.

PubMed

Gunbey, H P; Gunbey, E; Aslan, K; Bulut, T; Unal, A; Incesu, L

2017-06-01

Tinnitus is defined as an imaginary subjective perception in the absence of an external sound. Convergent evidence proposes that tinnitus perception includes auditory, attentional and emotional components. The aim of this study was to investigate the thalamic, auditory and limbic interactions associated with tinnitus-related distress by Diffusion Tensor Imaging (DTI). A total of 36 tinnitus patients, 20 healthy controls underwent an audiological examination, as well as a magnetic resonance imaging protocol including structural and DTI sequences. All participants completed the Tinnitus Handicap Inventory (THI) and Visual Analog Scales (VAS) related with tinnitus. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained for the auditory cortex (AC), inferior colliculus (IC), lateral lemniscus (LL), medial geniculate body (MGB), thalamic reticular nucleus (TRN), amygdala (AMG), hippocampus (HIP), parahippocampus (PHIP) and prefrontal cortex (PFC). In tinnitus patients the FA values of IC, MGB, TRN, AMG, HIP decreased and the ADC values of IC, MGB, TRN, AMG, PHIP increased significantly. The contralateral IC-LL and bilateral MGB FA values correlated negatively with hearing loss. A negative relation was found between the AMG-HIP FA values and THI and VAS scores. Bilateral ADC values of PHIP and PFC significantly correlated with the attention deficiency-VAS scores. In conclusion, this is the first DTI study to investigate the grey matter structures related to tinnitus perception and the significant correlation of FA and ADC with clinical parameters suggests that DTI can provide helpful information for tinnitus. Magnifying the microstructures in DTI can help evaluate the three faces of tinnitus nature: hearing, emotion and attention.

Differentiating prenatal exposure to methamphetamine and alcohol versus alcohol and not methamphetamine using tensor based brain morphometry and discriminant analysis

PubMed Central

Sowell, Elizabeth R.; Leow, Alex D.; Bookheimer, Susan Y.; Smith, Lynne M.; O’Connor, Mary J.; Kan, Eric; Rosso, Carly; Houston, Suzanne; Dinov, Ivo D.; Thompson, Paul M.

2010-01-01

Here we investigate the effects of prenatal exposure to methamphetamine (MA) on local brain volume using magnetic resonance imaging. Because many who use MA during pregnancy also use alcohol, a known teratogen, we examined whether local brain volumes differed among 61 children (ages 5 to 15), 21 with prenatal MA exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls (CON group). Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally, and right prefrontal and left occipitoparietal cortices. Striatal volume reductions were more severe in the MAA group than in the ALC group, and within the MAA group, a negative correlation between full-scale IQ (FSIQ) scores and caudate volume was observed. Limbic structures including the anterior and posterior cingulate, the inferior frontal gyrus (IFG) and ventral and lateral temporal lobes bilaterally were increased in volume in both exposure groups. Further, cingulate and right IFG volume increases were more pronounced in the MAA than ALC group. Discriminant function analyses using local volume measurements and FSIQ were used to predict group membership, yielding factor scores that correctly classified 72% of participants in jackknife analyses. These findings suggest that striatal and limbic structures, known to be sites of neurotoxicity in adult MA abusers, may be more vulnerable to prenatal MA exposure than alcohol exposure, and that more severe striatal damage is associated with more severe cognitive deficit. PMID:20237258

A Systematic and Meta-analytic Review of Neural Correlates of Functional Outcome in Schizophrenia.

PubMed

Wojtalik, Jessica A; Smith, Matthew J; Keshavan, Matcheri S; Eack, Shaun M

2017-10-21

Individuals with schizophrenia are burdened with impairments in functional outcome, despite existing interventions. The lack of understanding of the neurobiological correlates supporting adaptive function in the disorder is a significant barrier to developing more effective treatments. This research conducted a systematic and meta-analytic review of all peer-reviewed studies examining brain-functional outcome relationships in schizophrenia. A total of 53 (37 structural and 16 functional) brain imaging studies examining the neural correlates of functional outcome across 1631 individuals with schizophrenia were identified from literature searches in relevant databases occurring between January, 1968 and December, 2016. Study characteristics and results representing brain-functional outcome relationships were systematically extracted, reviewed, and meta-analyzed. Results indicated that better functional outcome was associated with greater fronto-limbic and whole brain volumes, smaller ventricles, and greater activation, especially during social cognitive processing. Thematic observations revealed that the dorsolateral prefrontal cortex, anterior cingulate, posterior cingulate, parahippocampal gyrus, superior temporal sulcus, and cerebellum may have role in functioning. The neural basis of functional outcome and disability is infrequently studied in schizophrenia. While existing evidence is limited and heterogeneous, these findings suggest that the structural and functional integrity of fronto-limbic brain regions is consistently related to functional outcome in individuals with schizophrenia. Further research is needed to understand the mechanisms and directionality of these relationships, and the potential for identifying neural targets to support functional improvement. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Examining Brain Morphometry Associated with Self-Esteem in Young Adults Using Multilevel-ROI-Features-Based Classification Method

PubMed Central

Peng, Bo; Lu, Jieru; Saxena, Aditya; Zhou, Zhiyong; Zhang, Tao; Wang, Suhong; Dai, Yakang

2017-01-01

Purpose: This study is to exam self-esteem related brain morphometry on brain magnetic resonance (MR) images using multilevel-features-based classification method. Method: The multilevel region of interest (ROI) features consist of two types of features: (i) ROI features, which include gray matter volume, white matter volume, cerebrospinal fluid volume, cortical thickness, and cortical surface area, and (ii) similarity features, which are based on similarity calculation of cortical thickness between ROIs. For each feature type, a hybrid feature selection method, comprising of filter-based and wrapper-based algorithms, is used to select the most discriminating features. ROI features and similarity features are integrated by using multi-kernel support vector machines (SVMs) with appropriate weighting factor. Results: The classification performance is improved by using multilevel ROI features with an accuracy of 96.66%, a specificity of 96.62%, and a sensitivity of 95.67%. The most discriminating ROI features that are related to self-esteem spread over occipital lobe, frontal lobe, parietal lobe, limbic lobe, temporal lobe, and central region, mainly involving white matter and cortical thickness. The most discriminating similarity features are distributed in both the right and left hemisphere, including frontal lobe, occipital lobe, limbic lobe, parietal lobe, and central region, which conveys information of structural connections between different brain regions. Conclusion: By using ROI features and similarity features to exam self-esteem related brain morphometry, this paper provides a pilot evidence that self-esteem is linked to specific ROIs and structural connections between different brain regions. PMID:28588470

Examining Brain Morphometry Associated with Self-Esteem in Young Adults Using Multilevel-ROI-Features-Based Classification Method.

PubMed

Peng, Bo; Lu, Jieru; Saxena, Aditya; Zhou, Zhiyong; Zhang, Tao; Wang, Suhong; Dai, Yakang

2017-01-01

Purpose: This study is to exam self-esteem related brain morphometry on brain magnetic resonance (MR) images using multilevel-features-based classification method. Method: The multilevel region of interest (ROI) features consist of two types of features: (i) ROI features, which include gray matter volume, white matter volume, cerebrospinal fluid volume, cortical thickness, and cortical surface area, and (ii) similarity features, which are based on similarity calculation of cortical thickness between ROIs. For each feature type, a hybrid feature selection method, comprising of filter-based and wrapper-based algorithms, is used to select the most discriminating features. ROI features and similarity features are integrated by using multi-kernel support vector machines (SVMs) with appropriate weighting factor. Results: The classification performance is improved by using multilevel ROI features with an accuracy of 96.66%, a specificity of 96.62%, and a sensitivity of 95.67%. The most discriminating ROI features that are related to self-esteem spread over occipital lobe, frontal lobe, parietal lobe, limbic lobe, temporal lobe, and central region, mainly involving white matter and cortical thickness. The most discriminating similarity features are distributed in both the right and left hemisphere, including frontal lobe, occipital lobe, limbic lobe, parietal lobe, and central region, which conveys information of structural connections between different brain regions. Conclusion: By using ROI features and similarity features to exam self-esteem related brain morphometry, this paper provides a pilot evidence that self-esteem is linked to specific ROIs and structural connections between different brain regions.

Beyond stereotypes of adolescent risk taking: Placing the adolescent brain in developmental context.

PubMed

Romer, Daniel; Reyna, Valerie F; Satterthwaite, Theodore D

2017-10-01

Recent neuroscience models of adolescent brain development attribute the morbidity and mortality of this period to structural and functional imbalances between more fully developed limbic regions that subserve reward and emotion as opposed to those that enable cognitive control. We challenge this interpretation of adolescent development by distinguishing risk-taking that peaks during adolescence (sensation seeking and impulsive action) from risk taking that declines monotonically from childhood to adulthood (impulsive choice and other decisions under known risk). Sensation seeking is primarily motivated by exploration of the environment under ambiguous risk contexts, while impulsive action, which is likely to be maladaptive, is more characteristic of a subset of youth with weak control over limbic motivation. Risk taking that declines monotonically from childhood to adulthood occurs primarily under conditions of known risks and reflects increases in executive function as well as aversion to risk based on increases in gist-based reasoning. We propose an alternative Life-span Wisdom Model that highlights the importance of experience gained through exploration during adolescence. We propose, therefore, that brain models that recognize the adaptive roles that cognition and experience play during adolescence provide a more complete and helpful picture of this period of development. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Supratentorial white matter blurring associated with voltage-gated potassium channel-complex limbic encephalitis.

PubMed

Urbach, H; Rauer, S; Mader, I; Paus, S; Wagner, J; Malter, M P; Prüss, H; Lewerenz, J; Kassubek, J; Hegen, H; Auer, M; Deisenhammer, F; Ufer, F; Bien, C G; Baumgartner, A

2015-12-01

Limbic encephalitis (LE) associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) is frequently non-paraneoplastic and associated with marked improvement following corticosteroid therapy. Mesial temporal lobe abnormalities are present in around 80 % of patients. If associated or preceded by faciobrachial dystonic seizures, basal ganglia signal changes may occur. In some patients, blurring of the supratentorial white matter on T2-weighted images (SWMB) may be seen. The purpose of this study was to evaluate the incidence of SWMB and whether it is specific for VGKC-LE. Two experienced neuroradiologists independently evaluated signal abnormalities on FLAIR MRI in 79 patients with LE while unaware on the antibody type. SWMB was independently assessed as present in 10 of 36 (28 %) compared to 2 (5 %) of 43 non-VGKC patients (p = 0.009). It was not related to the presence of LGI1 or CASPR2 proteins of VGKC antibodies. MRI showed increased temporomesial FLAIR signal in 22 (61 %) VGKC compared to 14 (33 %) non-VGKC patients (p = 0.013), and extratemporomesial structures were affected in one VGKC (3 %) compared to 11 (26 %) non-VGKC patients (p = 0.005). SWMB is a newly described MRI sign rather specific for VGKC-LE.

Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ackermann, R.F.; Lear, J.L.

We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered ({sup 18}F)fluorodeoxyglucose (FDG) and ({sup 14}C)-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GMg) and oxidative (GMo) glucose metabolism and is therefore related to total cerebral glucose metabolism GMt: GMg + GMo = GMt. With oxidative metabolism, the {sup 14}C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the {sup 14}C label is lost frommore » the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GMo than to GMt. If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMRglc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum.« less

Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption

PubMed Central

2014-01-01

One line summary Metabolic syndrome and obesity-related co-morbidities are largely explained by co-adaptations to the energy use of the large human brain in the cortico-limbic-striatal and NRF2 systems. The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal. The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated. The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A ‘dual system’ is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans. The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing ‘common or garden’ food, appears to have occurred. Insufficient consumption of food micronutrients prevents optimal human NRF2 function. Inefficient oxidation of excess energy forces central and non-adipose cells to store excess toxic lipid. Oxidative stress and metabolic inflammation, or metaflammation, allow susceptibility to infectious, degenerative atherosclerotic cardiovascular, autoimmune, neurodegenerative and dysplastic diseases. Other relevant human-specific co-adaptations are examined, and encompass the unusual ability to store fat, certain vitamin pathways, the generalised but flexible intestine and microbiota, and slow development and longevity. This theory has significant past and future corollaries, which are explored in a separate article by McGill, A-T, in Archives of Public Health, 72: 31. PMID:25708524

Psychophysiological correlates of aggression and violence: an integrative review.

PubMed

Patrick, Christopher J

2008-08-12

This paper reviews existing psychophysiological studies of aggression and violent behaviour including research employing autonomic, electrocortical and neuroimaging measures. Robust physiological correlates of persistent aggressive behaviour evident in this literature include low baseline heart rate, enhanced autonomic reactivity to stressful or aversive stimuli, enhanced EEG slow wave activity, reduced P300 brain potential response and indications from structural and functional neuroimaging studies of dysfunction in frontocortical and limbic brain regions that mediate emotional processing and regulation. The findings are interpreted within a conceptual framework that draws on two integrative models in the literature. The first is a recently developed hierarchical model of impulse control (externalizing) problems, in which various disinhibitory syndromes including aggressive and addictive behaviours of different kinds are seen as arising from common as well as distinctive aetiologic factors. This model represents an approach to organizing these various interrelated phenotypes and investigating their common and distinctive aetiologic substrates. The other is a neurobiological model that posits impairments in affective regulatory circuits in the brain as a key mechanism for impulsive aggressive behaviour. This model provides a perspective for integrating findings from studies employing different measures that have implicated varying brain structures and physiological systems in violent and aggressive behaviour.

Idiopathic REM Sleep Behavior Disorder in the development of Parkinson’s Disease

PubMed Central

Boeve, Bradley F.

2016-01-01

Summary Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with Lewy body disease (LBD) pathology in central and peripheral nervous system structures. While the etiology of PD is not fully understood, recent clinicopathologic analyses by Braak and colleagues have led to the development of a staging system of LBD pathology in the evolution of prototypical PD. This system posits a relatively predictable topography of progression of LBD pathology in the central nervous system, from olfactory structures and the medulla, which then progresses rostrally from the medulla to the pons, then midbrain/substantia nigra, then limbic, and then neocortical structures. If this topography and temporal evolution of LBD pathology indeed occur, one could hypothesize that other manifestations of LBD which reflect degeneration of olfactory and pontomedullary structures may begin many years prior to the development of prominent nigral degeneration and the associated parkinsonian features of classic PD. One such manifestation of prodromal PD is rapid eye movement (REM) sleep behavior disorder (RBD), which is a parasomnia manifested by vivid dreams associated with dream enactment behavior during REM sleep. Animal and human studies have implicated lesions or dysfunction in REM sleep and motor control circuitry in the pontomedullary structures cause RBD phenomenology, and degeneration of these structures could explain the presence of RBD years or decades prior to the onset of parkinsonism in those who develop PD. This review incorporates the rapidly growing literature on RBD and other prodromal features of PD as it pertains to the Braak staging system, and presents a framework from which many hypotheses can be (and already are being) tested. An important outcome of this framework will be to determine the natural history of RBD and associated features in the evolution to PD in the current era of no disease-modifying therapies – these natural history data will permit the development of clinical trail methodology with key measures and adequate power to detect if such therapies delay the onset or prevent the development of PD and associated morbidity. PMID:23578773

Postictal psychosis and its electrophysiological correlates in invasive EEG: a case report study and literature review.

PubMed

Kuba, Robert; Brázdil, Milan; Rektor, Ivan

2012-04-01

We identified two patients with medically refractory temporal lobe epilepsy, from whom intracranial EEG recordings were obtained at the time of postictal psychosis. Both patients had mesial temporal epilepsy associated with hippocampal sclerosis. In both patients, the postictal psychosis was associated with a continual "epileptiform" EEG pattern that differed from their interictal and ictal EEG findings (rhythmical slow wave and "abortive" spike-slow wave complex activity in the right hippocampus and lateral temporal cortex in case 1 and a periodic pattern of triphasic waves in the contacts recording activity from the left anterior cingulate gyrus). Some cases of postictal psychosis might be caused by the transient impairment of several limbic system structures due to the "continual epileptiform discharge" in some brain regions. Case 2 is the first report of a patient with TLE in whom psychotic symptoms were associated with the epileptiform impairment of the anterior cingulate gyrus. Copyright © 2012 Elsevier Inc. All rights reserved.

EMDR therapy for PTSD after motor vehicle accidents: meta-analytic evidence for specific treatment

PubMed Central

Boccia, Maddalena; Piccardi, Laura; Cordellieri, Pierluigi; Guariglia, Cecilia; Giannini, Anna Maria

2015-01-01

Motor vehicle accident (MVA) victims may suffer both acute and post-traumatic stress disorders (PTSD). With PTSD affecting social, interpersonal and occupational functioning, clinicians as well as the National Institute of Health are very interested in identifying the most effective psychological treatment to reduce PTSD. From research findings, eye movement desensitization and reprocessing (EMDR) therapy is considered as one of the effective treatment of PTSD. In this paper, we present the results of a meta-analysis of fMRI studies on PTSD after MVA through activation likelihood estimation. We found that PTSD following MVA is characterized by neural modifications in the anterior cingulate cortex (ACC), a cerebral structure involved in fear-conditioning mechanisms. Basing on previous findings in both humans and animals, which demonstrate that desensitization techniques and extinction protocols act on the limbic system, the effectiveness of EMDR and of cognitive behavioral therapies (CBT) may be related to the fact that during these therapies the ACC is stimulated by desensitization. PMID:25954183

Fornix as an imaging marker for episodic memory deficits in healthy aging and in various neurological disorders

PubMed Central

Douet, Vanessa; Chang, Linda

2015-01-01

The fornix is a part of the limbic system and constitutes the major efferent and afferent white matter tracts from the hippocampi. The underdevelopment of or injuries to the fornix are strongly associated with memory deficits. Its role in memory impairments was suggested long ago with cases of surgical forniceal transections. However, recent advances in brain imaging techniques, such as diffusion tensor imaging, have revealed that macrostructural and microstructural abnormalities of the fornix correlated highly with declarative and episodic memory performance. This structure appears to provide a robust and early imaging predictor for memory deficits not only in neurodegenerative and neuroinflammatory diseases, such as Alzheimer's disease and multiple sclerosis, but also in schizophrenia and psychiatric disorders, and during neurodevelopment and “typical” aging. The objective of the manuscript is to present a systematic review regarding published brain imaging research on the fornix, including the development of its tracts, its role in various neurological diseases, and its relationship to neurocognitive performance in human studies. PMID:25642186

Dissecting out conscious and unconscious memory (sub)processes within the human medial temporal lobe.

PubMed

Grunwald, T; Pezer, N; Münte, T F; Kurthen, M; Lehnertz, K; Van Roost, D; Fernández, G; Kutas, M; Elger, C E

2003-11-01

The human medial temporal lobe (MTL) system mediates memories that can be consciously recollected. However, the specific natures of the individual contributions of its various subregions to conscious memory processes remain equivocal. Here we show a functional dissociation between the hippocampus proper and the parahippocampal region in conscious and unconscious memory as revealed by invasive recordings of limbic event-related brain potentials recorded during explicit and implicit word recognition: Only hippocampal and not parahippocampal neural activity exhibits a sensitivity to the implicit versus explicit nature of the recognition memory task. Moreover, only within the hippocampus proper do the neural responses to repeated words differ not only from those to new words but also from each other as a function of recognition success. By contrast parahippocampal (rhinal) responses are sensitive to repetition independent of conscious recognition. These findings thus demonstrate that it is the hippocampus proper among the MTL structures that is specifically engaged during conscious memory processes.

Dreaming and cognition in patients with frontotemporal dysfunction.

PubMed

Paiva, Teresa; Bugalho, Paulo; Bentes, Carla

2011-12-01

Individuals with Parkinson's disease (PD) and temporal lobe epilepsy (TLE) have hallucinations and mild cognitive dysfunction. The objective of this work was to study dreams in PD and TLE patients using a common functional model of dream production involving the limbic and paralimbic structures. Dreams were characterised in early-stage PD (19 males) and TLE patients (52) with dream diaries classified by the Hall van de Castle system and were compared with matched controls. In PD, there were significant differences between patients' dreams and those of controls: animals, physical aggression, and a befriender were more common in patients, and aggressor and bodily misfortunes were less common. The dreams of patients with frontal dysfunction showed more aggressive features. TLE patients had lower recall than PD patients and a higher proportion of dreams involving family and familiar settings, lower proportions involving success, and a higher incidence of frontal dysfunction. The dreams of PD and TLE patients share important features. Copyright © 2011. Published by Elsevier Inc.

Preliminary fMRI findings concerning the influence of 5-HTP on food selection.

PubMed

Ioannou, Stephanos; Williams, Adrian L

2017-01-01

This functional magnetic resonance imaging study was designed to observe how physiological brain states can alter food preferences. A primary goal was to observe food-sensitive regions and moreover examine whether 5-HTP intake would activate areas which have been associated with appetite suppression, anorexia, satiety, and weight loss. Fourteen healthy male and female participants took part in the study, of which half of them received the supplement 5-HTP and the rest vitamin C (control) on an empty stomach. During the scanning session, they passively observed food (high calories, proteins, carbohydrates) and nonfood movie stimuli. Within the 5-HTP group, a comparison of food and nonfood stimuli showed significant responses that included the limbic system, the basal ganglia, and the prefrontal, temporal, and parietal cortices. For the vitamin C group, activity was mainly located in temporal and occipital regions. Compared to the vitamin C group, the 5-HTP group in response to food showed increased activation on the VMPFC, the DLPFC, limbic, and temporal regions. For the 5-HTP group, activity in response to food high in protein content compared to food high in calories and carbohydrates was located in the limbic system and the right caudomedial OFC, whereas for the vitamin C group, activity was mainly located at the inferior parietal lobes, the anterior cingulate gyri, and the left ventrolateral OFC. Greater responses to carbohydrates and high calorie stimuli in the vitamin C group were located at the right temporal gyrus, the occipital gyrus, the right VLPFC, whereas for the 5-HTP group, activity was observed at the left VMPFC, the parahippocampal gyrus bilaterally, the occipital lobe, and middle temporal gyri. In line with the hypotheses, 5-HTP triggered cortical responses associated with healthy body weight as well as cerebral preferences for protein-rich stimuli. The brain's activity is altered by macronutrients rich or deprived in the body. By reading the organisms physiological states and combining them with memory experiences, it constructs behavioral strategies steering an individual toward or in opposition to a particular food.

Cholangiocarcinoma associated with limbic encephalitis and early cerebral abnormalities detected by 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography-positron emission tomography: a case report.

PubMed

Schmidt, Sergio L; Schmidt, Juliana J; Tolentino, Julio C; Ferreira, Carlos G; de Almeida, Sergio A; Alvarenga, Regina P; Simoes, Eunice N; Schmidt, Guilherme J; Canedo, Nathalie H S; Chimelli, Leila

2016-07-20

Limbic encephalitis was originally described as a rare clinical neuropathological entity involving seizures and neuropsychological disturbances. In this report, we describe cerebral patterns visualized by positron emission tomography in a patient with limbic encephalitis and cholangiocarcinoma. To our knowledge, there is no other description in the literature of cerebral positron emission tomography findings in the setting of limbic encephalitis and subsequent diagnosis of cholangiocarcinoma. We describe a case of a 77-year-old Caucasian man who exhibited persistent cognitive changes 2 years before his death. A cerebral scan obtained at that time by 2-deoxy-2-[fluorine-18]fluoro- D -glucose integrated with computed tomography-positron emission tomography showed low radiotracer uptake in the frontal and temporal lobes. Cerebrospinal fluid analysis indicated the presence of voltage-gated potassium channel antibodies. Three months before the patient's death, a lymph node biopsy indicated a cholangiocarcinoma, and a new cerebral scan obtained by 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography-positron emission tomography showed an increment in the severity of metabolic deficit in the frontal and parietal lobes, as well as hypometabolism involving the temporal lobes. Two months before the patient's death, cerebral metastases were detected on a contrast-enhanced computed tomographic scan. Postmortem examination revealed a cholangiocarcinoma with multiple metastases including the lungs and lymph nodes. The patient's brain weighed 1300 g, and mild cortical atrophy, ex vacuo dilation of the ventricles, and mild focal thickening of the cerebellar leptomeninges, which were infiltrated by neoplastic epithelial cells, were observed. These findings support the need for continued vigilance in malignancy surveillance in patients with limbic encephalitis and early cerebral positron emission tomographic scan abnormalities. The difficulty in early diagnosis of small tumors, such as a cholangiocarcinoma, is discussed in the context of the clinical utility of early cerebral hypometabolism detected by 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography-positron emission tomography in patients with rapidly progressive dementia.

Pathological Joking or Witzelsucht Revisited.

PubMed

Granadillo, Elias D; Mendez, Mario F

2016-01-01

Humor, or the perception or elicitation of mirth and funniness, is distinguishable from laughter and can be differentially disturbed by neuropsychiatric disease. The authors describe two patients with constant joking, or Witzelsucht, in the absence of pseudobulbar affect and review the literature on pathological humor. These patients had involvement of frontal structures, impaired appreciation of nonsimple humor, and a compulsion for disinhibited joking. Current neuroscience suggests that impaired humor integration from right lateral frontal injury and disinhibition from orbitofrontal damage results in disinhibited humor, preferentially activating limbic and subcortical reward centers. Additional frontal-subcortical circuit dysfunction may promote pathological joking as a compulsion.

PATHOLOGICAL JOKING OR WITZELSUCHT REVISITED

PubMed Central

Granadillo, Elias; Mendez, Mario F.

2018-01-01

Humor, or the perception or elicitation of mirth and funniness, is distinguishable from laughter and can be differentially disturbed by neuropsychiatric disease. We present two patients with constant joking, or Witzelsucht, in the absence of pseudobulbar affect and review the literature on pathological humor. These patients had involvement of frontal structures, impaired appreciation of non-simple humor, and a compulsion for disinhibited joking. Current neuroscience suggests impaired humor integration from right lateral frontal injury and disinhibition from orbitofrontal damage results in disinhibited humor preferentially activating limbic and subcortical reward centers. Additional frontal-subcortical circuit dysfunction may promote pathological joking as a compulsion. PMID:26900737

The psychopath magnetized: insights from brain imaging

PubMed Central

Anderson, Nathaniel E.; Kiehl, Kent A.

2014-01-01

Psychopaths commit a disproportionate amount of violent crime, and this places a substantial economic and emotional burden on society. Elucidation of the neural correlates of psychopathy may lead to improved management and treatment of the condition. Although some methodological issues remain, the neuroimaging literature is generally converging on a set of brain regions and circuits that are consistently implicated in the condition: the orbitofrontal cortex, amygdala, and the anterior and posterior cingulate and adjacent (para)limbic structures. We discuss these findings in the context of extant theories of psychopathy and highlight the potential legal and policy implications of this body of work. PMID:22177031

Diagnosis, treatment, and neurobiology of autism in children.

PubMed

Lainhart, J E; Piven, J

1995-08-01

Autism is a developmental neuropsychiatric disorder defined by the presence of social and communicative deficits, restricted and repetitive behaviors and interests, and a characteristic course. Research suggests that hereditary factors play a principal role in the etiology of most cases. A phenotype broader than autism, including milder social and language-based cognitive deficits, appears to be inherited. Although the pathogenesis is unknown, neurobiologic mechanisms clearly underlie the disorder. Neuropathologic studies have demonstrated abnormalities in limbic structures, the cerebellum, and the cortex. New advances in behavioral therapies and pharmacologic treatment are important components of successful multidisciplinary treatment of this disorder.

Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

PubMed Central

Miller, Thomas D.; Chong, Trevor T.-J.; Aimola Davies, Anne M.; Ng, Tammy W.C.; Johnson, Michael R.; Irani, Sarosh R.; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A.

2017-01-01

Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. PMID:28369215

Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

PubMed

Ciumas, Carolina; Lindström, Per; Aoun, Bernard; Savic, Ivanka

2008-01-15

Metabolic and neuro-receptor abnormalities within the extrafocal limbic circuits are established in mesial temporal lobe epilepsy (MTLE). However, very little is known about how these circuits process external stimuli. We tested whether odor activation can help delineate limbic functional disintegration in MTLE, and measured cerebral blood flow with PET during birhinal smelling of familiar and unfamiliar odors, using smelling of odorless air as the baseline condition. Patients with MTLE (13 left-sided, 10 right-sided) and 21 controls were investigated. In addition to odor activation, the analysis included functional connectivity, using right and left piriform cortex as seed regions. Healthy controls activated the amygdala, piriform, anterior insular, and cingulate cortices on both sides. Smelling of familiar odors engaged, in addition, the right parahippocampus, and the left Brodmann Area (BA) 44, 45, 47. Patients failed to activate the amygdala, piriform and the anterior insular cortex in the epileptogenic hemisphere. Furthermore, those with left MTLE did not activate the left BA 44, 45 and 47 with familiar odors, which they perceived as less familiar than controls. Congruent with the activation data each seed region was in patients functionally disconnected with the contralateral amygdala+piriform+insular cortex. The functional disintegration in patients exceeded the reduced activation, and included the contralateral temporal neocortex, and in subjects with right MTLE also the right orbitofrontal cortex. Imaging of odor perception may be used to delineate functional disintegration of the limbic networks in MTLE. It shows an altered response in several regions, which may underlie some interictal behavioral problems associated with this condition.

Changes in artistic style and behaviour in Parkinson's disease: dopamine and creativity.

PubMed

Kulisevsky, Jaime; Pagonabarraga, Javier; Martinez-Corral, Mercè

2009-05-01

We present a PD patient in whom dopamine agonists awoke a hidden creativity that led to a gradual increase in painting productivity evolving to a disruptive impulsive behaviour that shared many features with punding. A dramatic change in painting style related to a more emotional experience during the process of creation developed after treatment onset. This case suggests that changes in creativity in PD seem to be related to dopaminergic imbalance in the limbic system.

Chemosensory danger detection in the human brain: Body odor communicating aggression modulates limbic system activation.

PubMed

Mutic, Smiljana; Brünner, Yvonne F; Rodriguez-Raecke, Rea; Wiesmann, Martin; Freiherr, Jessica

2017-05-01

Although the sense of smell is involved in numerous survival functions, the processing of body odor emitted by dangerous individuals is far from understood. The aim of the study was to explore how human fight chemosignals communicating aggression can alter brain activation related to an attentional bias and danger detection. While the anterior cingulate cortex (ACC) was seen involved in processing threat-related emotional information, danger detection and error evaluation, it still remains unknown whether human chemosignals communicating aggression can potentially modulate this activation. In the fMRI experiment, healthy male and female normosmic odor recipients (n=18) completed a higher-order processing task (emotional Stroop task with the word categories anger, anxiety, happiness and neutral) while exposed to aggression and exercise chemosignals (collected from a different group of healthy male donors; n=16). Our results provide first evidence that aggression chemosignals induce a time-sensitive attentional bias in chemosensory danger detection and modulate limbic system activation. During exposure to aggression chemosignals compared to exercise chemosignals, functional imaging data indicates an enhancement of thalamus, hypothalamus and insula activation (p<.05, FWE-corrected). Together with the thalamus, the ACC was seen activated in response to threat-related words (p<.001). Chemosensory priming and habituation to body odor signals are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of morphine on brain plasticity.

PubMed

Beltrán-Campos, V; Silva-Vera, M; García-Campos, M L; Díaz-Cintra, S

2015-04-01

Morphine shares with other opiates and drugs of abuse the ability to modify the plasticity of brain areas that regulate the morphology of dendrites and spines, which are the primary sites of excitatory synapses in regions of the brain involved in incentive motivation, rewards, and learning. In this review we discuss the impact of morphine use during the prenatal period of brain development and its long-term consequences in murines, and then link those consequences to similar effects occurring in human neonates and adults. Repeated exposure to morphine as treatment for pain in terminally ill patients produces long-term changes in the density of postsynaptic sites (dendrites and spines) in sensitive areas of the brain, such as the prefrontal cortex, the limbic system (hippocampus, amygdala), and caudate nuclei and nucleus accumbens. This article reviews the cellular mechanisms and receptors involved, primarily dopaminergic and glutamatergic receptors, as well as synaptic plasticity brought about by changes in dendritic spines in these areas. The actions of morphine on both developing and adult brains produce alterations in the plasticity of excitatory postsynaptic sites of the brain areas involved in limbic system functions (reward and learning). Doctors need further studies on plasticity in dendrites and spines and on signaling molecules, such as calcium, in order to improve treatments for addiction. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Implication of mGlu5 receptor in the enhancement of morphine-induced hyperlocomotion under chronic treatment with zolpidem.

PubMed

Shibasaki, Masahiro; Ishii, Kazunori; Masukawa, Daiki; Ando, Koji; Ikekubo, Yuiko; Ishikawa, Yutori; Shibasaki, Yumiko; Mori, Tomohisa; Suzuki, Tsutomu

2014-09-05

Long-term exposure to zolpidem induces drug dependence, and it is well known that the balance between the GABAergic and glutamatergic systems plays a critical role in maintaining the neuronal network. In the present study, we investigated the interaction between GABAA receptor α1 subunit and mGlu5 receptor in the limbic forebrain including the N.Acc. after treatment with zolpidem for 7 days. mGlu5 receptor protein levels were significantly increased after treatment with zolpidem for 7 days, and this change was accompanied by the up-regulation of phospholipase Cβ1 and calcium/calmodulin-dependent protein kinase IIα, which are downstream of mGlu5 receptor in the limbic forebrain. To confirm that mGlu5 receptor is directly involved in dopamine-related behavior in mice following chronic treatment with zolpidem, we measured morphine-induced hyperlocomotion after chronic treatment with zolpidem in the presence or absence of an mGlu5 receptor antagonist. Although chronic treatment with zolpidem significantly enhanced morphine-induced hyperlocomotion, this enhancement of morphine-induced hyperlocomotion was suppressed by treating it with the mGlu5 receptor antagonist MPEP. These results suggest that chronic treatment with zolpidem caused neural plasticity in response to activation of the mesolimbic dopaminergic system accompanied by an increase in mGlu5 receptor. Copyright © 2014 Elsevier B.V. All rights reserved.

Study of tonotopic brain changes with functional MRI and FDG-PET in a patient with unilateral objective cochlear tinnitus.

PubMed

Guinchard, A-C; Ghazaleh, Naghmeh; Saenz, M; Fornari, E; Prior, J O; Maeder, P; Adib, S; Maire, R

2016-11-01

We studied possible brain changes with functional MRI (fMRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) in a patient with a rare, high-intensity "objective tinnitus" (high-level SOAEs) in the left ear of 10 years duration, with no associated hearing loss. This is the first case of objective cochlear tinnitus to be investigated with functional neuroimaging. The objective cochlear tinnitus was measured by Spontaneous Otoacoustic Emissions (SOAE) equipment (frequency 9689 Hz, intensity 57 dB SPL) and is clearly audible to anyone standing near the patient. Functional modifications in primary auditory areas and other brain regions were evaluated using 3T and 7T fMRI and FDG-PET. In the fMRI evaluations, a saturation of the auditory cortex at the tinnitus frequency was observed, but the global cortical tonotopic organization remained intact when compared to the results of fMRI of healthy subjects. The FDG-PET showed no evidence of an increase or decrease of activity in the auditory cortices or in the limbic system as compared to normal subjects. In this patient with high-intensity objective cochlear tinnitus, fMRI and FDG-PET showed no significant brain reorganization in auditory areas and/or in the limbic system, as reported in the literature in patients with chronic subjective tinnitus. Copyright © 2016 Elsevier B.V. All rights reserved.

The brain endocannabinoid system in the regulation of energy balance.

PubMed

Richard, Denis; Guesdon, Benjamin; Timofeeva, Elena

2009-02-01

The role played by the endocannabinoid system in the regulation of energy balance is currently generating a great amount of interest among several groups of investigators. This interest in large part comes from the urgent need to develop anti-obesity and anti-cachexia drugs around target systems (such as the endocannabinoid system), which appears to be genuinely involved in energy balance regulation. When activated, the endocannabinoid system favors energy deposition through increasing energy intake and reducing energy expenditure. This system is activated in obesity and following food deprivation, which further supports its authentic function in energy balance regulation. The cannabinoid receptor type 1 (CB1), one of the two identified cannabinoid receptors, is expressed in energy-balance brain structures that are also able to readily produce or inactivate N-arachidonoyl ethanolamine (anandamide) and 2-arachidonoylglycerol (2AG), the most abundantly formed and released endocannabinoids. The brain action of endocannabinoid system on energy balance seems crucial and needs to be delineated in the context of the homeostatic and hedonic controls of food intake and energy expenditure. These controls require the coordinated interaction of the hypothalamus, brainstem and limbic system and it appears imperative to unravel those interplays. It is also critical to investigate the metabolic endocannabinoid system while considering the panoply of functions that the endocannabinoid system fulfills in the brain and other tissues. This article aims at reviewing the potential mechanisms whereby the brain endocannabinoid system influences the regulation energy balance.

Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology.

PubMed

Hultman, Rainbo; Mague, Stephen D; Li, Qiang; Katz, Brittany M; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D; Dzirasa, Kafui

2016-07-20

Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1 Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

Capgras syndrome associated with limbic encephalitis in a patient with diffuse large B-cell lymphoma

PubMed Central

Soares, Herval Ribeiro; Cavalcante, Wagner Cid Palmeira; Martins, Sebastião Nunes; Smid, Jerusa; Nitrini, Ricardo

2016-01-01

ABSTRACT We report the case of a patient with insidious onset and slowly progressive cognitive impairment, behavioral symptoms, temporal lobe seizures and delusional thoughts typical of delusional misidentification syndromes. Clinical presentation along with extensive diagnostic work-up revealed limbic encephalitis secondary to diffuse large B-cell lymphoma. The patient underwent immunotherapy with high-dose corticosteroid but no significant improvement was observed. No specific treatment for lymphoma was performed because the patient died of septic shock following a nosocomial respiratory infection. Delusional misidentification syndromes are an unusual and unique form of cognitive impairment in which a patient consistently misidentifies persons, places, objects, or events. Capgras syndrome is the most common subtype of this disorder, being defined by the recurrent and transient belief that someone close has been substituted by an imposter. These entities are generally associated with neurodegenerative diseases and psychiatric disturbances. Rare reports of associations between misidentification syndromes and autoimmune diseases such as multiple sclerosis have been published, but no papers address a correlation with limbic encephalitis or lymphoma. PMID:29213434

The Subthalamic Nucleus, Limbic Function, and Impulse Control.

PubMed

Rossi, P Justin; Gunduz, Aysegul; Okun, Michael S

2015-12-01

It has been well documented that deep brain stimulation (DBS) of the subthalamic nucleus (STN) to address some of the disabling motor symptoms of Parkinson's disease (PD) can evoke unintended effects, especially on non-motor behavior. This observation has catalyzed more than a decade of research concentrated on establishing trends and identifying potential mechanisms for these non-motor effects. While many issues remain unresolved, the collective result of many research studies and clinical observations has been a general recognition of the role of the STN in mediating limbic function. In particular, the STN has been implicated in impulse control and the related construct of valence processing. A better understanding of STN involvement in these phenomena could have important implications for treating impulse control disorders (ICDs). ICDs affect up to 40% of PD patients on dopamine agonist therapy and approximately 15% of PD patients overall. ICDs have been reported to be associated with STN DBS. In this paper we will focus on impulse control and review pre-clinical, clinical, behavioral, imaging, and electrophysiological studies pertaining to the limbic function of the STN.

[Oxytocin: the hormone of love, trust and social bond. Clinical use in autism and social phobia].

PubMed

Martin-Du Pan, R C

2012-03-21

Oxytocin, an octapeptide synthesized in the hypothalamus, stimulates milk election and uterine contractions. In the brain this hormone acts as a neuropeptide. It could inhibit through the GABAergic system the activity of limbic amygdala, which is involved in the response to fear. Oxytocin could also induce the protective behaviour of the mother towards its offspring through the dopaminergic system. In mankind, oxytocin plays a role in trust, empathy, generosity, stress and sexuality. Clinical studies are testing potential benefits of oxytocin administration in autism, depression and social phobia. Results are still preliminary.

Decreased sound tolerance: hyperacusis, misophonia, diplacousis, and polyacousis.

PubMed

Jastreboff, Pawel J; Jastreboff, Margaret M

2015-01-01

Definitions, potential mechanisms, and treatments for decreased sound tolerance, hyperacusis, misophonia, and diplacousis are presented with an emphasis on the associated physiologic and neurophysiological processes and principles. A distinction is made between subjects who experience these conditions versus patients who suffer from them. The role of the limbic and autonomic nervous systems and other brain systems involved in cases of bothersome decreased sound tolerance is stressed. The neurophysiological model of tinnitus is outlined with respect to how it may contribute to our understanding of these phenomena and their treatment. © 2015 Elsevier B.V. All rights reserved.

CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal - a pilot study.

PubMed

Kraus, Thomas; Kiess, Olga; Hösl, Katharina; Terekhin, Pavel; Kornhuber, Johannes; Forster, Clemens

2013-09-01

It has recently been shown that electrical stimulation of sensory afferents within the outer auditory canal may facilitate a transcutaneous form of central nervous system stimulation. Functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) effects in limbic and temporal structures have been detected in two independent studies. In the present study, we investigated BOLD fMRI effects in response to transcutaneous electrical stimulation of two different zones in the left outer auditory canal. It is hypothesized that different central nervous system (CNS) activation patterns might help to localize and specifically stimulate auricular cutaneous vagal afferents. 16 healthy subjects aged between 20 and 37 years were divided into two groups. 8 subjects were stimulated in the anterior wall, the other 8 persons received transcutaneous vagus nervous stimulation (tVNS) at the posterior side of their left outer auditory canal. For sham control, both groups were also stimulated in an alternating manner on their corresponding ear lobe, which is generally known to be free of cutaneous vagal innervation. Functional MR data from the cortex and brain stem level were collected and a group analysis was performed. In most cortical areas, BOLD changes were in the opposite direction when comparing anterior vs. posterior stimulation of the left auditory canal. The only exception was in the insular cortex, where both stimulation types evoked positive BOLD changes. Prominent decreases of the BOLD signals were detected in the parahippocampal gyrus, posterior cingulate cortex and right thalamus (pulvinar) following anterior stimulation. In subcortical areas at brain stem level, a stronger BOLD decrease as compared with sham stimulation was found in the locus coeruleus and the solitary tract only during stimulation of the anterior part of the auditory canal. The results of the study are in line with previous fMRI studies showing robust BOLD signal decreases in limbic structures and the brain stem during electrical stimulation of the left anterior auditory canal. BOLD signal decreases in the area of the nuclei of the vagus nerve may indicate an effective stimulation of vagal afferences. In contrast, stimulation at the posterior wall seems to lead to unspecific changes of the BOLD signal within the solitary tract, which is a key relay station of vagal neurotransmission. The results of the study show promise for a specific novel method of cranial nerve stimulation and provide a basis for further developments and applications of non-invasive transcutaneous vagus stimulation in psychiatric patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Changes in endocannabinoid and N-acylethanolamine levels in rat brain structures following cocaine self-administration and extinction training.

PubMed

Bystrowska, Beata; Smaga, Irena; Frankowska, Małgorzata; Filip, Małgorzata

2014-04-03

Preclinical investigations have demonstrated that drugs of abuse alter the levels of lipid-based signalling molecules, including endocannabinoids (eCBs) and N-acylethanolamines (NAEs), in the rodent brain. In addition, several drugs targeting eCBs and/or NAEs are implicated in reward and/or seeking behaviours related to the stimulation of dopamine systems in the brain. In our study, the brain levels of eCBs (anandamide (AEA) and 2-arachidonoylglycerol (2-AG)) and NAEs (oleoylethanolamide (OEA) and palmitoylethanolamide (PEA)) were analyzed via an LC-MS/MS method in selected brain structures of rats during cocaine self-administration and after extinction training according to the "yoked" control procedure. Repeated (14days) cocaine (0.5mg/kg/infusion) self-administration and yoked drug delivery resulted in a significant decrease (ca. 52%) in AEA levels in the cerebellum, whereas levels of 2-AG increased in the frontal cortex, the hippocampus and the cerebellum and decreased in the hippocampus and the dorsal striatum. In addition, we detected increases (>150%) in the levels of OEA and PEA in the limbic areas in both cocaine treated groups, as well as an increase in the tissue levels of OEA in the dorsal striatum in only the yoked cocaine group and increases in the tissue levels of PEA in the dorsal striatum (both cocaine groups) and the nucleus accumbens (yoked cocaine group only). Compared to the yoked saline control group, extinction training (10days) resulted in a potent reduction in AEA levels in the frontal cortex, the hippocampus and the nucleus accumbens and in 2-AG levels in the hippocampus, the dorsal striatum and the cerebellum. The decreases in the limbic and subcortical areas were more apparent for rats that self-administered cocaine. Following extinction, there was a region-specific change in the levels of NAEs in rats previously injected with cocaine; a potent increase (ca. 100%) in the levels of OEA and PEA was detected in the prefrontal cortex and the hippocampus, whilst a drop was noted in the striatal areas versus yoked saline yoked animals. Our findings support the previous pharmacological evidence that the eCB system and NAEs are involved in reinforcement and extinction of positively reinforced behaviours and that these lipid-derived molecules may represent promising targets for the development of new treatments for drug addiction. Copyright © 2014 Elsevier Inc. All rights reserved.

Structural and functional MRI- findings in children and adolescents with antisocial behavior.

PubMed

Vloet, Timo D; Konrad, Kerstin; Huebner, Thomas; Herpertz, Sabine; Herpertz-Dahlmann, Beate

2008-01-01

The developmental course of children with conduct disorder (CD) is heterogeneous. Especially children who exhibit symptoms early in their lifetimes are characterized by a negative outcome. Neurobiological aspects of CD have been investigated in these children but little is known about structural and functional brain aberrations. We describe the developmental taxonomy of children with CD and focus on those with the early onset subtype. Structural MRI data of these children and antisocial adults are recapitulated. The impact of investigating neurobiological underpinnings of antisocial behavior and how this might contribute to future forensic and psychiatric assessments is discussed. RESULTS/ CONCLUSION: Children display similar structural aberrations of fronto-limbic structures to adults with antisocial behavior, and amygdala dysfunction might be closely related to dysregulated emotions. Though the investigation of biological factors in antisocial subjects has made great progress in recent years, today MRI is still a rather complex, expensive and indistinct method for forensic assessment. (c) 2008 John Wiley & Sons, Ltd.

Tinnitus distress is linked to enhanced resting-state functional connectivity from the limbic system to the auditory cortex.

PubMed

Chen, Yu-Chen; Xia, Wenqing; Chen, Huiyou; Feng, Yuan; Xu, Jin-Jing; Gu, Jian-Ping; Salvi, Richard; Yin, Xindao

2017-05-01

The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age-, sex-, and education-matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus patients demonstrated abnormal directional connectivity of the amygdala and hippocampus, including primary and association auditory cortex, and other non-auditory areas. Importantly, scores on the Tinnitus Handicap Questionnaires were positively correlated with increased connectivity from the left amygdala to left superior temporal gyrus (r = 0.570, P = 0.005), and from the right amygdala to right superior temporal gyrus (r = 0.487, P = 0.018). Moreover, enhanced effective connectivity from the right hippocampus to left transverse temporal gyrus was correlated with tinnitus duration (r = 0.452, P = 0.030). The results showed that tinnitus distress strongly correlates with enhanced effective connectivity that is directed from the amygdala to the auditory cortex. The longer the phantom sensation, the more likely acute tinnitus becomes permanently encoded by memory traces in the hippocampus. Hum Brain Mapp 38:2384-2397, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Evidence that NMDA-dependent limbic neural plasticity in the right hemisphere mediates pharmacological stressor (FG-7142)-induced lasting increases in anxiety-like behavior. Study 1--Role of NMDA receptors in efferent transmission from the cat amygdala.

PubMed

Adamec, R E

1998-01-01

The anxiogenic beta-carboline, FG-7142, produces intense anxiety in humans and anxiety-like behavior in animals. FG-7142 also mimics the effects of exogenous stressors. In cats, FG-7142 lastingly changes defensive and aggressive behavior. Long-term potentiation (LTP) of neural transmission between limbic structures known to modulate feline defensive response to threat accompany behavioral changes. A series of three reports describes experiments designed to test the hypothesis that behavioral changes depend upon an N-methyl-D-aspartate (NMDA) receptor-based LTP of efferent transmission from the amygdala. This first study characterizes the dose and time effects of injection of the NMDA receptor blocker 7-amino-phosphono-heptanoic acid (AP7) on efferent transmission from the cat amygdala to the ventromedial hypothalamus (VMH). Effects of doses of 0.5-10mg/kg (i.v.) of AP7 on potentials evoked in the VMH by single pulse stimulation of the basal amygdala were examined. In order to localize the action of the drug, concurrent measurements were taken of potentials evoked in the VMH by stimulation of the efferent fibers from the amygdala to the VMH (ventral amygdalofugal pathway, VAF). There was a dose-dependent reduction in the amygdalo-VMH evoked potential. The greatest reduction occurred at 5 mg/kg. Effects peaked at 10 min, and persisted for at least 1 h after injection. In contrast, AP7 increased the VAF-VMH-evoked potential at 10 min after injection, with a maximal increase at 5mg/kg. The data suggest that NMDA receptors intrinsic to the amygdala modulate excitatory efferent transmission from amygdala to VMH in the cat. It is speculated that a glutamatergic projection to gamma-aminobutyric acid tonic inhibitory systems in the VMH accounts for the VAF-VMH results.

Effect of enhanced geomagnetic activity on hypothermia and mortality in rats

NASA Astrophysics Data System (ADS)

Bureau, Y. R. J.; Persinger, M. A.; Parker, G. H.

1996-12-01

The hypothesis was investigated that variability in the severity of limbic seizure-induced hypothermia in rats was affected by ambient geomagnetic activity. Data were obtained in support of this hypothesis. The depth of the hypothermia was significantly ( P < 0.001) reduced if the ambient geomagnetic activity exceeded 35 nT to 40 nT. Mortality during the subsequent 5 days was increased when the geomagnetic activity was > 20 nT. The magnitude of the effect was comparable to the difference between exposure to light or to darkness during the 20 h after the induction of limbic seizures.

Superior limbic keratoconjunctivitis associated with cosmetic soft contact lens wear.

PubMed

Fuerst, D J; Sugar, J; Worobec, S

1983-08-01

Thirteen patients who wore soft contact lenses were seen with a syndrome consistent with superior limbic keratoconjunctivitis. An irregular epithelial surface, punctate staining with fluorescein, and subepithelial infiltrates were found on the superior aspect of the corneas in association with hyperemia of the superior bulbar conjunctivae. The keratoconjunctivitis persisted as long as 15 months after discontinuation of lens wear. Patch testing with ophthalmic vehicle preservatives, performed on seven patients, failed to show a consistent hypersensitivity to any of the tested compounds, and three patients had used only preservative-free saline for lens care. The etiology of this syndrome is unknown.

Caspr2 antibody limbic encephalitis is associated with Hashimoto thyroiditis and thymoma.

PubMed

Lee, Chih-Hong; Lin, Jainn-Jim; Lin, Kun-Ju; Chang, Bao-Luen; Hsieh, Hsiang-Yao; Chen, Wei-Hsun; Lin, Kuang-Lin; Fung, Hon-Chung; Wu, Tony

2014-06-15

Contactin-associated protein 2 (Caspr2) antibody is a neuronal surface antibody (NSAb) capable of causing disorders involving central and peripheral nervous systems (PNS). Thymoma can be found in patients with Caspr2 antibodies and is most frequently associated with PNS symptoms. Myasthenia gravis can be found in these patients, but Hashimoto thyroiditis (HT) has not been reported. A 76-year-old woman presented with sub-acute-onset changes in mental status. Further investigations revealed thymoma and HT. The presence of NSAb was tested by immunofluorescence on human embryonic kidney-293 cells. Treatment included corticosteroids, azathioprine, thyroxine, plasmapheresis, and thymectomy. Caspr2 antibody was positive in serum but absent in CSF. Brain magnetic resonance imaging (MRI) showed diffuse cortical atrophy, but did not change significantly after treatments. Brain positron emission tomography (PET) revealed diffuse hypometabolism over the cerebral cortex. The patient's mental status only partially improved. In Caspr2 antibody-associated syndromes, thymoma can occur in patients presenting only with LE, and HT can be an accompanying disease. Brain MRI and PET may not show specific lesions in limbic area. Patients with Caspr2 antibodies and thymoma may not have good prognosis. Copyright © 2014 Elsevier B.V. All rights reserved.

[Update on Herpes Simplex Encephalitis].

PubMed

Kuroda, Hiroshi

2015-07-01

Herpes simplex encephalitis (HSE), which is caused by the herpes simplex virus (HSV), is a severe neuro-infectious disease characterized by high mortality and morbidity. We reviewed the pathomechanism, diagnosis, and treatment of HSE based on recent progress in the field. The highlighted mechanism of HSE in this review is immune-mediated tissue damage caused by host immunity. Major symptoms of HSE include psychiatric alteration, Klüver-Bucy syndrome, and amnesia, caused by frequent involvement of the limbic system. An important differential diagnosis of HSE is autoimmune limbic encephalitis, including anti-N-methyl-D-aspartate receptor encephalitis, and anti-voltage-gated K⁺ channel encephalitis. HSE is definitely diagnosed based on the detection of HSV-DNA by polymerase chain reaction and/or the detection of HSV-IgG antibody in the cerebrospinal fluid (CSF). Repeated CSF examinations are required for the accurate diagnosis of HSE. Acyclovir (ACV) plays a central role in the treatment of HSE, and its early initiation is essential for good outcome in patients with HSE. Acute administration of corticosteroids for HSE is controversial; a randomized, double-blind, placebo-controlled trial to investigate the efficacy of add-on corticosteroids to ACV is ongoing.

Metacognitive Control of Categorial Neurobehavioral Decision Systems

PubMed Central

Foxall, Gordon R.

2016-01-01

The competing neuro-behavioral decision systems (CNDS) model proposes that the degree to which an individual discounts the future is a function of the relative hyperactivity of an impulsive system based on the limbic and paralimbic brain regions and the relative hypoactivity of an executive system based in prefrontal cortex (PFC). The model depicts the relationship between these categorial systems in terms of the antipodal neurophysiological, behavioral, and decision (cognitive) functions that engender normal and addictive responding. However, a case may be made for construing several components of the impulsive and executive systems depicted in the model as categories (elements) of additional systems that are concerned with the metacognitive control of behavior. Hence, this paper proposes a category-based structure for understanding the effects on behavior of CNDS, which includes not only the impulsive and executive systems of the basic model but a superordinate level of reflective or rational decision-making. Following recent developments in the modeling of cognitive control which contrasts Type 1 (rapid, autonomous, parallel) processing with Type 2 (slower, computationally demanding, sequential) processing, the proposed model incorporates an arena in which the potentially conflicting imperatives of impulsive and executive systems are examined and from which a more appropriate behavioral response than impulsive choice emerges. This configuration suggests a forum in which the interaction of picoeconomic interests, which provide a cognitive dimension for CNDS, can be conceptualized. This proposition is examined in light of the resolution of conflict by means of bundling. PMID:26925004

Repeated restraint stress-induced atrophy of glutamatergic pyramidal neurons and decreases in glutamatergic efflux in the rat amygdala are prevented by the antidepressant agomelatine.

PubMed

Grillo, C A; Risher, M; Macht, V A; Bumgardner, A L; Hang, A; Gabriel, C; Mocaër, E; Piroli, G G; Fadel, J R; Reagan, L P

2015-01-22

Major depressive illness is among the most prevalent neuropsychiatric disorders and is associated with neuroplasticity deficits in limbic structures such as the amygdala. Since exposure to stressful life events is proposed to contribute to depressive illness, our recent studies examined the effects of stress on amygdalar neuroplasticity. These studies determined that repeated stress elicits deficits in glutamatergic activity in the amygdala, neuroplasticity deficits that can be prevented by some but not all antidepressants. In view of these observations, the goal of the current study was to determine the effects of repeated restraint stress (RRS) on the dendritic architecture of pyramidal neurons in the rat basolateral nucleus of the amygdala (CBL), as well as glutamate efflux in the CBL and central nucleus of the amygdala (CMX) via in vivo microdialysis. We also examined the ability of the antidepressant agomelatine to prevent RRS-induced neuroplasticity deficits. Compared with control rats, rats subjected to RRS exhibited atrophy of CBL pyramidal neurons, including decreases in total dendritic length, branch points, and dendritic complexity index. In addition, glutamate efflux was significantly reduced in the CMX of rats subjected to RRS, thereby identifying a potential neurochemical consequence of stress-induced dendritic atrophy of CBL pyramidal neurons. Lastly, an acute stress challenge increased corticosterone (CORT) levels in the CBL, suggesting that stress-induced increases in CORT levels may contribute to the neuroanatomical and neurochemical effects of RRS in the CBL. Importantly, these RRS-induced changes were prevented by daily agomelatine administration. These results demonstrate that the neuroanatomical and neurochemical properties of glutamatergic neurons in the rat amygdala are adversely affected by repeated stress and suggest that the therapeutic effects of agomelatine may include protection of structural and neurochemical plasticity in limbic structures like the amygdala. Published by Elsevier Ltd.

The neural markers of MRI to differentiate depression and panic disorder.

PubMed

Lai, Chien-Han

2018-04-27

Depression and panic disorder (PD) share the common pathophysiology from the perspectives of neurotransmitters. The relatively high comorbidity between depression and PD contributes to the substantial obstacles to differentiate from depression and PD, especially for the brain pathophysiology. There are significant differences in the diagnostic criteria between depression and PD. However, the paradox of similar pathophysiology and different diagnostic criteria in these two disorders were still the issues needing to be addressed. Therefore the clarification of potential difference in the field of neuroscience and pathophysiology between depression and PD can help the clinicians and scientists to understand more comprehensively about significant differences between depression and PD. The researchers should be curious about the underlying difference of pathophysiology beneath the significant distinction of clinical symptoms. In this review article, I tried to find some evidences for the differences between depression and PD, especially for neural markers revealed by magnetic resonance imaging (MRI). The distinctions of structural and functional alterations in depression and PD are reviewed. From the structural perspectives, PD seems to have less severe gray matter alterations in frontal and temporal lobes than depression. The study of white matter microintegrity reveals more widespread alterations in fronto-limbic circuit of depression patients than PD patients, such as the uncinate fasciculus and anterior thalamic radiation. PD might have a more restrictive pattern of structural alterations when compared to depression. For the functional perspectives, the core site of depression pathophysiology is the anterior subnetwork of resting-state network, such as anterior cingulate cortex, which is not significantly altered in PD. A possibly emerging pattern of fronto-limbic distinction between depression and PD has been revealed by these explorative reports. The future trend for machine learning and pattern recognition might confirm the differentiation pattern between depression and PD based on the explorative results. Copyright © 2018 Elsevier Inc. All rights reserved.

Increased hippocampal, thalamus and amygdala volume in long-term lithium-treated bipolar I disorder patients compared with unmedicated patients and healthy subjects.

PubMed

López-Jaramillo, Carlos; Vargas, Cristian; Díaz-Zuluaga, Ana M; Palacio, Juan David; Castrillón, Gabriel; Bearden, Carrie; Vieta, Eduard

2017-02-01

Magnetic resonance imaging (MRI) studies in bipolar I disorder (BD-I) suggest that lithium is associated with increased volumes of cortico-limbic structures. However, more rigorous control of confounding factors is needed to obtain further support for this hypothesis. The aim of the present study was to assess differences in brain volumes among long-term lithium-treated BD-I patients, unmedicated BD-I patients, and healthy controls. This was a cross-sectional study with 32 euthymic BD-I patients (16 on lithium monotherapy for a mean of 180 months, and 16 receiving no medication for at least the 2 months prior to the study) and 20 healthy controls. Patients were euthymic (Hamilton Depression Rating Scale [HDRS] <6 and Young Mania Rating Scale [YMRS] <7) and had not taken psychotropic medications other than lithium for at least 6 months. Brain images were acquired on a 1.5 Tesla MRI (Phillips, Amsterdam, The Netherlands) and segmented to generate volumetric measures of cortical and subcortical brain areas, ventricles and global brain. Significant differences were found in the volumes of the left amygdala (P=.0003), right amygdala (P=.030), left hippocampus (P=.022), left thalamus (P=.022), and right thalamus (P=.019) in long-term lithium-treated BD-I patients, compared to unmedicated patients and controls, after multivariable adjustment. No differences were observed in global brain volume or in ventricular size among the three groups. Likewise, there was no correlation between serum lithium levels and the increase in size in the described brain areas. The structural differences found among the three groups, and specifically those between long-term lithium-treated and unmedicated BD-I patients, indicate increased limbic structure volumes in lithium-treated patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reward deficiency and anti-reward in pain chronification.

PubMed

Borsook, D; Linnman, C; Faria, V; Strassman, A M; Becerra, L; Elman, I

2016-09-01

Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypodopaminergia, clinically manifested anhedonia, and diminished motivation for natural reinforcers. Anti-reward (AR) conversely pertains to a between-systems neuroadaptation involving over-recruitment of key limbic structures (e.g., the central and basolateral amygdala nuclei, the bed nucleus of the stria terminalis, the lateral tegmental noradrenergic nuclei of the brain stem, the hippocampus and the habenula) responsible for massive outpouring of stressogenic neurochemicals (e.g., norepinephrine, corticotropin releasing factor, vasopressin, hypocretin, and substance P) giving rise to such negative affective states as anxiety, fear and depression. We propose here the Combined Reward deficiency and Anti-reward Model (CReAM), in which biopsychosocial variables modulating brain reward, motivation and stress functions can interact in a 'downward spiral' fashion to exacerbate the intensity, chronicity and comorbidities of chronic pain syndromes (i.e., pain chronification). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

An Implementation Guide for the Experimental Application of Suggestive-Accelerative Learning and Teaching to the Coast Guard Training Environment.

DTIC Science & Technology

1986-06-01

33). Evidence exists that shows an increase in environmental stimulation has an impact on the number of nerve calls produced by the brain and the...language, auditory discriminatioh, somasensory functions, olfactory, visual processes, and motor control related to the higher functions. In some...shown to control emotions and motivation. The limbic system can be thought of as controlling "the four F’s--feeding, fighting, fleeing, and sexual

Atypical nucleus accumbens morphology in psychopathy: another limbic piece in the puzzle.

PubMed

Boccardi, Marina; Bocchetta, Martina; Aronen, Hannu J; Repo-Tiihonen, Eila; Vaurio, Olli; Thompson, Paul M; Tiihonen, Jari; Frisoni, Giovanni B

2013-01-01

Psychopathy has been associated with increased putamen and striatum volumes. The nucleus accumbens - a key structure in reversal learning, less effective in psychopathy - has not yet received specific attention. Moreover, basal ganglia morphology has never been explored. We examined the morphology of the caudate, putamen and accumbens, manually segmented from magnetic resonance images of 26 offenders (age: 32.5 ± 8.4) with medium-high psychopathy (mean PCL-R=30 ± 5) and 25 healthy controls (age: 34.6 ± 10.8). Local differences were statistically modeled using a surface-based radial distance mapping method (p<0.05; multiple comparisons correction through permutation tests). In psychopathy, the caudate and putamen had normal global volume, but different morphology, significant after correction for multiple comparisons, for the right dorsal putamen (permutation test: p=0.02). The volume of the nucleus accumbens was 13% smaller in psychopathy (p corrected for multiple comparisons <0.006). The atypical morphology consisted of predominant anterior hypotrophy bilaterally (10-30%). Caudate and putamen local morphology displayed negative correlation with the lifestyle factor of the PCL-R (permutation test: p=0.05 and 0.03). From these data, psychopathy appears to be associated with an atypical striatal morphology, with highly significant global and local differences of the accumbens. This is consistent with the clinical syndrome and with theories of limbic involvement. Copyright © 2013 Elsevier Ltd. All rights reserved.

The functional neuroanatomy of bipolar disorder: a consensus model

PubMed Central

Strakowski, Stephen M; Adler, Caleb M; Almeida, Jorge; Altshuler, Lori L; Blumberg, Hilary P; Chang, Kiki D; DelBello, Melissa P; Frangou, Sophia; McIntosh, Andrew; Phillips, Mary L; Sussman, Jessika E; Townsend, Jennifer D

2013-01-01

Objectives Functional neuroimaging methods have proliferated in recent years, such that functional magnetic resonance imaging, in particular, is now widely used to study bipolar disorder. However, discrepant findings are common. A workgroup was organized by the Department of Psychiatry, University of Cincinnati (Cincinnati, OH, USA) to develop a consensus functional neuroanatomic model of bipolar I disorder based upon the participants’ work as well as that of others. Methods Representatives from several leading bipolar disorder neuroimaging groups were organized to present an overview of their areas of expertise as well as focused reviews of existing data. The workgroup then developed a consensus model of the functional neuroanatomy of bipolar disorder based upon these data. Results Among the participants, a general consensus emerged that bipolar I disorder arises from abnormalities in the structure and function of key emotional control networks in the human brain. Namely, disruption in early development (e.g., white matter connectivity, prefrontal pruning) within brain networks that modulate emotional behavior leads to decreased connectivity among ventral prefrontal networks and limbic brain regions, especially amygdala. This developmental failure to establish healthy ventral prefrontal–limbic modulation underlies the onset of mania and ultimately, with progressive changes throughout these networks over time and with affective episodes, a bipolar course of illness. Conclusions This model provides a potential substrate to guide future investigations and areas needing additional focus are identified. PMID:22631617

Chronic Pain and Chronic Stress: Two Sides of the Same Coin?

PubMed

Abdallah, Chadi G; Geha, Paul

2017-02-01

Pain and stress share significant conceptual and physiological overlaps. Both phenomena challenge the body's homeostasis and necessitate decision-making to help animals adapt to their environment. In addition, chronic stress and chronic pain share a common behavioral model of failure to extinguish negative memories. Yet, they also have discrepancies such that the final brain endophenotype of posttraumatic stress disorder, depression, and chronic pain appears to be different among the three conditions, and the role of the hypothalamic-pituitary-adrenal axis remains unclear in the physiology of pain. Persistence of either stress or pain is maladaptive and could lead to compromised well-being. In this brief review, we highlight the commonalities and differences between chronic stress and chronic pain, while focusing particularly on the central role of the limbic brain. We assess the current attempts in the field to conceptualize and understand chronic pain, within the context of knowledge gained from the stress literature. The limbic brain-including hippocampus, amygdala, and ventromedial pre-frontal cortex-plays a critical role in learning. These brain areas integrate incoming nociceptive or stress signals with internal state, and generate learning signals necessary for decision-making. Therefore, the physiological and structural remodeling of this learning circuitry is observed in conditions such as chronic pain, depression, and posttraumatic stress disorder, and is also linked to the risk of onset of these conditions.

Integration of transcriptomic and cytoarchitectonic data implicates a role for MAOA and TAC1 in the limbic-cortical network.

PubMed

Bludau, Sebastian; Mühleisen, Thomas W; Eickhoff, Simon B; Hawrylycz, Michael J; Cichon, Sven; Amunts, Katrin

2018-06-01

Decoding the chain from genes to cognition requires detailed insights how areas with specific gene activities and microanatomical architectures contribute to brain function and dysfunction. The Allen Human Brain Atlas contains regional gene expression data, while the JuBrain Atlas offers three-dimensional cytoarchitectonic maps reflecting interindividual variability. To date, an integrated framework that combines the analytical benefits of both scientific platforms towards a multi-level brain atlas of adult humans was not available. We have, therefore, developed JuGEx, a new method for integrating tissue transcriptome and cytoarchitectonic segregation. We investigated differential gene expression in two JuBrain areas of the frontal pole that we have structurally and functionally characterized in previous studies. Our results show a significant upregulation of MAOA and TAC1 in the medial area frontopolaris which is a node in the limbic-cortical network and known to be susceptible for gray matter loss and behavioral dysfunction in patients with depression. The MAOA gene encodes an enzyme which is involved in the catabolism of dopamine, norepinephrine, serotonin, and other monoaminergic neurotransmitters. The TAC1 locus generates hormones that play a role in neuron excitations and behavioral responses. Overall, JuGEx provides a new tool for the scientific community that empowers research from basic, cognitive and clinical neuroscience in brain regions and disease models with regard to gene expression.

Have we been ignoring the elephant in the room? Seven arguments for considering the cerebellum as part of addiction circuitry.

PubMed

Miquel, Marta; Vazquez-Sanroman, Dolores; Carbo-Gas, María; Gil-Miravet, Isis; Sanchis-Segura, Carla; Carulli, Daniela; Manzo, Jorge; Coria-Avila, Genaro A

2016-01-01

Addiction involves alterations in multiple brain regions that are associated with functions such as memory, motivation and executive control. Indeed, it is now well accepted that addictive drugs produce long-lasting molecular and structural plasticity changes in corticostriatal-limbic loops. However, there are brain regions that might be relevant to addiction other than the prefrontal cortex, amygdala, hippocampus and basal ganglia. In addition to these circuits, a growing amount of data suggests the involvement of the cerebellum in many of the brain functions affected in addicts, though this region has been overlooked, traditionally, in the addiction field. Therefore, in the present review we provide seven arguments as to why we should consider the cerebellum in drug addiction. We present and discuss compelling evidence about the effects of drugs of abuse on cerebellar plasticity, the involvement of the cerebellum in drug-induced cue-related memories, and several findings showing that the instrumental memory and executive functions also recruit the cerebellar circuitry. In addition, a hypothetical model of the cerebellum's role relative to other areas within corticostriatal-limbic networks is also provided. Our goal is not to review animal and human studies exhaustively but to support the inclusion of cerebellar alterations as a part of the physiopathology of addiction disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy

PubMed Central

de Curtis, Marco; Gnatkovsky, Vadym; Gotman, Jean; Köhling, Rüdiger; Lévesque, Maxime; Manseau, Frédéric; Shiri, Zahra; Williams, Sylvain

2016-01-01

Low-voltage fast (LVF) and hypersynchronous (HYP) patterns are the seizure-onset patterns most frequently observed in intracranial EEG recordings from mesial temporal lobe epilepsy (MTLE) patients. Both patterns also occur in models of MTLE in vivo and in vitro, and these studies have highlighted the predominant involvement of distinct neuronal network/neurotransmitter receptor signaling in each of them. First, LVF-onset seizures in epileptic rodents can originate from several limbic structures, frequently spread, and are associated with high-frequency oscillations in the ripple band (80–200 Hz), whereas HYP onset seizures initiate in the hippocampus and tend to remain focal with predominant fast ripples (250–500 Hz). Second, in vitro intracellular recordings from principal cells in limbic areas indicate that pharmacologically induced seizure-like discharges with LVF onset are initiated by a synchronous inhibitory event or by a hyperpolarizing inhibitory postsynaptic potential barrage; in contrast, HYP onset is associated with a progressive impairment of inhibition and concomitant unrestrained enhancement of excitation. Finally, in vitro optogenetic experiments show that, under comparable experimental conditions (i.e., 4-aminopyridine application), the initiation of LVF- or HYP-onset seizures depends on the preponderant involvement of interneuronal or principal cell networks, respectively. Overall, these data may provide insight to delineate better therapeutic targets in the treatment of patients presenting with MTLE and, perhaps, with other epileptic disorders as well. PMID:27075542

Individual differences in local gray and white matter volumes reflect differences in temperament and character: a voxel-based morphometry study in healthy young females.

PubMed

Van Schuerbeek, Peter; Baeken, Chris; De Raedt, Rudi; De Mey, Johan; Luypaert, Rob

2011-01-31

The psychobiological personality model of Cloninger distinguishes four heritable temperament traits (harm avoidance (HA), novelty seeking (NS), reward dependence (RD) and persistence (P)) and three character traits (self-directedness (SD), cooperativeness (CO) and self-transcendence (ST)) which develop during lifetime. Prior research already showed that individual differences in temperament are reflected in structural variances in specific brain areas. In this study, we used voxel-based morphometry (VBM) to correlate the different temperament and character traits with local gray and white matter volumes (GMV and WMV) in young healthy female volunteers. We found correlations between the temperament traits and GMV and WMV in the frontal, temporal and limbic regions involved in controlling and generating the corresponding behavior as proposed in Cloninger's theory: anxious for HA, impulsive for NS, reward-directed for RD and goal-directed for P. The character traits correlated with GMV and WMV in the frontal, temporal and limbic regions involved in the corresponding cognitive tasks: self-reflection for SD, mentalizing and empathizing with others for CO and religious belief for ST. This study shows that individual variations in brain morphology can be related to the temperament and character dimensions, and lends support to the hypothesis of a neurobiological basis of personality traits. Copyright © 2010 Elsevier B.V. All rights reserved.

A locus on mouse Ch10 influences susceptibility to limbic seizure severity: fine mapping and in silico candidate gene analysis

PubMed Central

Winawer, Melodie R.; Klassen, Tara L.; Teed, Sarah; Shipman, Marissa; Leung, Emily H.; Palmer, Abraham A.

2014-01-01

Identification of genes contributing to mouse seizure susceptibility can reveal novel genes or pathways that provide insight into human epilepsy. Using mouse chromosome substitution strains and interval-specific congenic strains (ISCS), we previously identified an interval conferring pilocarpine-induced limbic seizure susceptibility on distal mouse Chromosome 10 (Ch10). We narrowed the region by generating subcongenics with smaller A/J Ch10 segments on a C57BL/6J (B6) background and tested them with pilocarpine. We also tested pilocarpine susceptible congenics for 6Hz ECT, another model of limbic seizure susceptibility, to determine whether the susceptibility locus might have a broad effect on neuronal hyperexcitability across more than one mode of limbic seizure induction. ISCS Line 1, which contained the distal 2.7 Mb segment from A/J (starting at rs29382217), was more susceptible to both pilocarpine and ECT. Line 2, which was a subcongenic of Line1 (starting at rs13480828), was not susceptible; thus defining a 1.0 Mb critical region that was unique to Line1. Bioinformatic approaches identified 52 human orthologues within the unique Line 1 susceptibility region, the majority syntenic to human Ch12. Applying an epilepsy network analysis of known and suspected excitability genes and examination of interstrain genomic and brain expression differences revealed novel candidates within the region. These include Stat2, which plays a role in hippocampal GABA receptor expression after status epilepticus, and novel candidates Pan2, Cdk2, Gls2, and Cs, which are involved in neural cell differentiation, cellular remodeling, and embryonic development. Our strategy may facilitate discovery of novel human epilepsy genes. PMID:24373497

Prevention of status epilepticus-induced brain edema and neuronal cell loss by repeated treatment with high-dose levetiracetam.

PubMed

Itoh, Kouichi; Inamine, Moriyoshi; Oshima, Wataru; Kotani, Masaharu; Chiba, Yoichi; Ueno, Masaki; Ishihara, Yasuhiro

2015-05-22

The management of status epilepticus (SE) is important to prevent mortality and the development of post-SE symptomatic epilepsy. Acquired epilepsy after an initial brain insult by SE can be experimentally reproduced in the murine model of SE induced by pilocarpine. In the present study, we evaluated the possibility of treatment with a high-dose of levetiracetam in this model. Repeated treatment with high-dose levetiracetam after termination of SE by diazepam significantly prevented the incidence of spontaneous recurrent seizures and mortality for at least 28 days. To determine the brain alterations after SE, magnetic resonance imaging was performed. Both T2-weighted imaging and diffusion-weighted imaging showed changes in the limbic regions. These changes in the limbic regions demonstrated the development of cytotoxic edema three hours after SE, followed by the development of vasogenic edema two days after SE. In the pilocarpine-SE model, the incidence of spontaneous recurrent seizures after SE was strongly associated with neuronal damage within a few hours to days after SE by the development of vasogenic edema via the breakdown of the blood-brain barrier in the limbic regions. High-dose levetiracetam significantly suppressed the parameters in the limbic areas. These data indicate that repeated treatment with high-dose levetiracetam for at least two days after SE termination by diazepam is important for controlling the neuronal damage by preventing brain edema. Therefore, these findings suggest that early treatment with high-dose levetiracetam after SE termination by diazepam may protect against adverse sequelae via the inhibition of neurotoxicity induced by brain edema events. Copyright © 2015 Elsevier B.V. All rights reserved.

Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis.

PubMed

Miller, Thomas D; Chong, Trevor T-J; Aimola Davies, Anne M; Ng, Tammy W C; Johnson, Michael R; Irani, Sarosh R; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A; Rosenthal, Clive R

2017-05-01

Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Mechanistic comparisons of functional domains across pediatric and adult bipolar disorder highlight similarities, as well as differences, influenced by the developing brain.

PubMed

Wegbreit, Ezra; Pavuluri, Mani

2012-01-01

Recent neuroimaging studies have uncovered much about the specific neural deficits in adult bipolar disorder (ABD), but despite promising results, neuroimaging research for pediatric bipolar disorder (PBD) is still developing. The neuroimaging literature is highly heterogeneous, varying in the paradigms used and in participants' mood states and medication status. Despite this variability, several dominant patterns emerge. In response to emotional stimuli, both ABD and PBD show limbic hyperactivity coupled with hypoactivity in ventral prefrontal emotion regulation systems. This pattern occurred most robustly in response to negative incidental stimuli and was especially apparent in manic PBD. ABD showed more variability in ventral prefrontal activity, possibly due to maturational and medication factors. On numerous cognitive paradigms, PBD showed dorsal prefrontal hypoactivity linked to ventral dysfunction, whereas ABD showed compensatory frontal, parietal, and temporal activity with paradigm-specific variations. In emotion-cognition interaction paradigms, patients show dysregulation in regions interfacing between cognitive and emotional brain systems (e.g., ventral prefrontal and cingulate cortices), which expend extra effort to process emotional stimuli effectively and recruit additional posterior attention systems to cope with affective instability. In addition, novel functional connectivity techniques have uncovered connectivity deficits between frontal and limbic regions in ABD and PBD at rest and during active emotional and cognitive tasks. Finally, the neuroimaging literature currently lacks cross-sectional studies comparing PBD with ABD and longitudinal studies following children and adolescents with BD into adulthood. Such studies would provide important insights into patients' prognosis and would determine targets for early interventions in the evolving illness diathesis.

Extensive distribution of glial cytoplasmic inclusions in an autopsied case of multiple system atrophy with a prolonged 18-year clinical course.

PubMed

Masui, Kenta; Nakata, Yukako; Fujii, Naoki; Iwaki, Toru

2012-02-01

We describe herein an autopsied case of multiple system atrophy (MSA) with prolonged clinical course of 18 years, and evaluate the extent of neurodegeneration and glial cytoplasmic inclusions (GCIs) in the entire brain of this rare case. A 64-year-old woman presented with typical neurological symptoms and imaging features of MSA. Thereafter, she became bedridden, and breathing was assisted through a tracheostomy for 12 years. She died at the age of 82 after 18 years from the initial symptom. Post mortem examination revealed severe neurodegeneration in the inferior olive, pontine nuclei, substantia nigra, locus ceruleus, putamen and cerebellum. Notably, phosphorylated α-synuclein (p-α-syn)-positive GCIs were found in these areas, but their number was very low. In contrast, the density of GCIs was much higher in such regions as the tectum/tegmentum of the brainstem, pyramidal tracts, neocortices and limbic system, which usually contain a small number of GCIs. Another constituent of GCIs, ubiquitin (Ub) and Ub-associated autophagy substrate p62, were also positive in some GCIs, and distribution of Ub/p62 immunoreactivity was proportionate to that of p-α-syn+ GCIs despite the very long duration of the disease. Furthermore, this case had complicated hypoxic encephalopathy, but p-α-syn+ GCIs were also found in the damaged white matter, indicating the contribution of α-syncleinopathy as well as hypoxic effect to the secondary myelin and axonal loss in the white matter. Together, this rare case suggests the contribution of the disease duration to the prevalence of GCIs, and the possible involvement of the limbic system in extensive-stage disease. © 2011 Japanese Society of Neuropathology.

A framework for understanding and advancing intertemporal choice research using rodent models

PubMed Central

Fobbs, Wambura C.; Mizumori, Sheri J. Y.

2017-01-01

Intertemporal choices are common and consequential to private and public life. Thus, there is considerable interest in understanding the neural basis of intertemporal decision making. In this minireview, we briefly describe conceptual and psychological perspectives on intertemporal choice and then provide a comprehensive evaluation of the neural structures and signals that comprise the underlying cortico-limbic-striatal circuit. Even though great advances have been made, our understanding of the neurobiology of intertemporal choice is still in its infancy because of the complex and dynamic nature of this form of decision making. We close by briefly discussing recommendations for the future study of intertemporal choice research. PMID:28065715

Limbic Encephalitis Manifesting as Selective Amnesia and Seizure-like Activity: A Case Report

PubMed Central

Kim, So-Yeon; Um, Yoo Hyun; Lim, Sung Chul

2018-01-01

Limbic encephalitis (LE) is characterized by short-term memory loss, disorientation, agitation, seizures, and histopathological evidence of medial temporal lobe inflammation. Leucine-rich, glioma inactivated 1 (LGI-1) is an auto-antigen associated with LE. We report a 37-year-old male patient with LGI-1-related LE who presented with recurrent episodes of selective amnesia, seizure-like activity, confusion, and personality change. His symptoms were significantly improved with steroid therapy. Thorough differential diagnosis with consideration for autoimmune encephalitis should be in patients with presentation of symptoms, such as memory impairment, personality change and seizure-like activity, especially when other neurological diagnoses are excluded. PMID:29397673

Impaired Frontal-Limbic White Matter Maturation in Children at Risk for Major Depression.

PubMed

Hung, Yuwen; Saygin, Zeynep M; Biederman, Joseph; Hirshfeld-Becker, Dina; Uchida, Mai; Doehrmann, Oliver; Han, Michelle; Chai, Xiaoqian J; Kenworthy, Tara; Yarmak, Pavel; Gaillard, Schuyler L; Whitfield-Gabrieli, Susan; Gabrieli, John D E

2017-09-01

Depression is among the most common neuropsychiatric disorders. It remains unclear whether brain abnormalities associated with depression reflect the pathological state of the disease or neurobiological traits predisposing individuals to depression. Parental history of depression is a risk factor that more than triples the risk of depression. We compared white matter (WM) microstructure cross-sectionally in 40 children ages 8-14 with versus without parental history of depression (At-Risk vs. Control). There were significant differences in age-related changes of fractional anisotropy (FA) between the groups, localized in the anterior fronto-limbic WM pathways, including the anterior cingulum and the genu of the corpus callosum. Control children exhibited typical increasing FA with age, whereas At-Risk children exhibited atypical decreasing FA with age in these fronto-limbic regions. Furthermore, dorsal cingulate FA significantly correlated with depressive symptoms for At-Risk children. The results suggest maturational WM microstructure differences in mood-regulatory neurocircuitry that may contribute to neurodevelopmental risk for depression. The study provides new insights into neurodevelopmental susceptibility to depression and related disabilities that may promote early preventive intervention approaches. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Beta and gamma oscillatory activities associated with olfactory memory tasks: different rhythms for different functional networks?

PubMed Central

Martin, Claire; Ravel, Nadine

2014-01-01

Olfactory processing in behaving animals, even at early stages, is inextricable from top down influences associated with odor perception. The anatomy of the olfactory network (olfactory bulb, piriform, and entorhinal cortices) and its unique direct access to the limbic system makes it particularly attractive to study how sensory processing could be modulated by learning and memory. Moreover, olfactory structures have been early reported to exhibit oscillatory population activities easy to capture through local field potential recordings. An attractive hypothesis is that neuronal oscillations would serve to “bind” distant structures to reach a unified and coherent perception. In relation to this hypothesis, we will assess the functional relevance of different types of oscillatory activity observed in the olfactory system of behaving animals. This review will focus primarily on two types of oscillatory activities: beta (15–40 Hz) and gamma (60–100 Hz). While gamma oscillations are dominant in the olfactory system in the absence of odorant, both beta and gamma rhythms have been reported to be modulated depending on the nature of the olfactory task. Studies from the authors of the present review and other groups brought evidence for a link between these oscillations and behavioral changes induced by olfactory learning. However, differences in studies led to divergent interpretations concerning the respective role of these oscillations in olfactory processing. Based on a critical reexamination of those data, we propose hypotheses on the functional involvement of beta and gamma oscillations for odor perception and memory. PMID:25002840

White Matter Integrity, Substance Use, and Risk Taking in Adolescence

PubMed Central

Jacobus, Joanna; Thayer, Rachel E.; Trim, Ryan S.; Bava, Sunita; Frank, Lawrence R.; Tapert, Susan F.

2012-01-01

White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n=47) and demographically similar non-users (n=49) received diffusion tensor imaging at baseline (ages 16–19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17–20). Brain regions of interest were: fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance using youth (n=47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 =10–12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (ΔR2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic system fibers and future substance use frequency. Subcortical white matter coherence along with an imbalance between the maturation levels in cognitive control and reward systems may disadvantage the resistance to engage in risk taking behaviors during adolescence. PMID:22564204

White matter integrity, substance use, and risk taking in adolescence.

PubMed

Jacobus, Joanna; Thayer, Rachel E; Trim, Ryan S; Bava, Sunita; Frank, Lawrence R; Tapert, Susan F

2013-06-01

White matter development is important for efficient communication between brain regions, higher order cognitive functioning, and complex behaviors. Adolescents have a higher propensity for engaging in risky behaviors, yet few studies have explored associations between white matter integrity and risk taking directly. Altered white matter integrity in mid-adolescence was hypothesized to predict subsequent risk taking behaviors 1.5 years later. Adolescent substance users (predominantly alcohol and marijuana, n = 47) and demographically similar nonusers (n = 49) received diffusion tensor imaging at baseline (ages 16-19), and risk taking measures at both baseline and an 18-month follow-up (i.e., at ages 17-20). Brain regions of interest were the fornix, superior corona radiata, superior longitudinal fasciculus, and superior fronto-occipital fasciculus. In substance-using youth (n = 47), lower white matter integrity at baseline in the fornix and superior corona radiata predicted follow-up substance use (ΔR2 = 10-12%, ps < .01), and baseline fornix integrity predicted follow-up delinquent behaviors (ΔR2 = 10%, p < .01) 1.5 years later. Poorer fronto-limbic white matter integrity was linked to a greater propensity for future risk taking behaviors among youth who initiated heavy substance use by mid-adolescence. Most notable were relationships between projection and limbic-system fibers and future substance-use frequency. Subcortical white matter coherence, along with an imbalance between the maturation levels in cognitive control and reward systems, may disadvantage the resistance to engage in risk taking behaviors during adolescence. 2013 APA, all rights reserved

Speech Disfluency-dependent Amygdala Activity in Adults Who Stutter: Neuroimaging of Interpersonal Communication in MRI Scanner Environment.

PubMed

Toyomura, Akira; Fujii, Tetsunoshin; Yokosawa, Koichi; Kuriki, Shinya

2018-03-15

Affective states, such as anticipatory anxiety, critically influence speech communication behavior in adults who stutter. However, there is currently little evidence regarding the involvement of the limbic system in speech disfluency during interpersonal communication. We designed this neuroimaging study and experimental procedure to sample neural activity during interpersonal communication between human participants, and to investigate the relationship between the amygdala activity and speech disfluency. Participants were required to engage in live communication with a stranger of the opposite sex in the MRI scanner environment. In the gaze condition, the stranger gazed at the participant without speaking, while in the live conversation condition, the stranger asked questions that the participant was required to answer. The stranger continued to gaze silently at the participant while the participant answered. Adults who stutter reported significantly higher discomfort than fluent controls during the experiment. Activity in the right amygdala, a key anatomical region in the limbic system involved in emotion, was significantly correlated with stuttering occurrences in adults who stutter. Right amygdala activity from pooled data of all participants also showed a significant correlation with discomfort level during the experiment. Activity in the prefrontal cortex, which forms emotion regulation neural circuitry with the amygdala, was decreased in adults who stutter than in fluent controls. This is the first study to demonstrate that amygdala activity during interpersonal communication is involved in disfluent speech in adults who stutter. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

The correlated network of acupuncture effect: a functional connectivity study.

PubMed

Qin, Wei; Tian, Jie; Pan, Xiaohong; Yang, Lin; Zhen, Zonglei

2006-01-01

A functional connectivity, which are temporally correlated in functionally related brain regions, before and after acupuncture manipulation was measured by MRI. Amygdala, as the control system of endogenetic analgesia, was selected for "seed" point. We found that compelling similarity existed in the network of resting state before and after acupuncture manipulation. A paired student t-test was implemented to investigate under the different conditions. The main difference was found in the limbic system, brainstem and cerebellum. We conclude that the default endogenous analgesia functional network exists in human brain at a low level, and it could be increased to a higher level by acupuncture modulation.

The impact of stress on the structure of the adolescent brain: Implications for adolescent mental health.

PubMed

Romeo, Russell D

2017-01-01

Adolescent development is associated with major changes in emotional and cognitive functions, as well as a rise in stress-related psychological disorders such as anxiety and depression. It is also a time of significant maturation of the brain, marked by structural alterations in many limbic and cortical regions. Though many elegant human neuroimaging studies have described the adolescent-related changes in these regions, relatively little is known about these changes in non-human animals. Moreover, both human and non-human data are lacking on how exposure to chronic stress may disrupt this structural maturation. Given the fundamental structure-function relationship in the nervous system, it will be important to understand how these normative and stress-induced structural alterations during adolescence influence psychological function, which in turn can modify future neural development. The purpose of this brief review is to describe the impact of stress on the structure of brain regions that continue to show structural maturation during adolescence and are highly sensitive to the effects of chronic stress exposure. Specifically, this review will focus on the amygdala, hippocampal formation, and prefrontal cortex, particularly from a morphological perspective. As many unanswered questions remain in this area of investigation, potential future lines of research are also discussed. A deeper appreciation of how stress affects adolescent brain development will be needed if we are to gain a better understanding of the mechanisms that mediate the increase in stress-related psychological dysfunctions often observed during this stage of development. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

Predictive brain networks for major depression in a semi-multimodal fusion hierarchical feature reduction framework.

PubMed

Yang, Jie; Yin, Yingying; Zhang, Zuping; Long, Jun; Dong, Jian; Zhang, Yuqun; Xu, Zhi; Li, Lei; Liu, Jie; Yuan, Yonggui

2018-02-05

Major depressive disorder (MDD) is characterized by dysregulation of distributed structural and functional networks. It is now recognized that structural and functional networks are related at multiple temporal scales. The recent emergence of multimodal fusion methods has made it possible to comprehensively and systematically investigate brain networks and thereby provide essential information for influencing disease diagnosis and prognosis. However, such investigations are hampered by the inconsistent dimensionality features between structural and functional networks. Thus, a semi-multimodal fusion hierarchical feature reduction framework is proposed. Feature reduction is a vital procedure in classification that can be used to eliminate irrelevant and redundant information and thereby improve the accuracy of disease diagnosis. Our proposed framework primarily consists of two steps. The first step considers the connection distances in both structural and functional networks between MDD and healthy control (HC) groups. By adding a constraint based on sparsity regularization, the second step fully utilizes the inter-relationship between the two modalities. However, in contrast to conventional multi-modality multi-task methods, the structural networks were considered to play only a subsidiary role in feature reduction and were not included in the following classification. The proposed method achieved a classification accuracy, specificity, sensitivity, and area under the curve of 84.91%, 88.6%, 81.29%, and 0.91, respectively. Moreover, the frontal-limbic system contributed the most to disease diagnosis. Importantly, by taking full advantage of the complementary information from multimodal neuroimaging data, the selected consensus connections may be highly reliable biomarkers of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuroanatomical Differences between Men and Women in Help-Seeking Coping Strategy

PubMed Central

Li, Hai-Jiang; Sun, Jiang-Zhou; Zhang, Qing-Lin; Wei, Dong-Tao; Li, Wen-Fu; Jackson, Todd; Hitchman, Glenn; Qiu, Jiang

2014-01-01

Help seeking (HS) is a core coping strategy that is directed towards obtaining support, advice, or assistance as means of managing stress. Women have been found to use more HS than men. Neural correlates of sex differences have also been reported in prefrontal-limbic system (PLS) regions that are linked to stress and coping, yet structural differences between men and women relating to HS in the PLS are still unknown. Thus, the association between gray matter volume (GMV) and HS was investigated using voxel-based morphometry (VBM) in a large healthy sample (126 men and 156 women). Results indicated women reported more HS than men did. VBM results showed that the relation between HS scores and GMV differed between men and women in regions of the bilateral orbitofrontal cortex extending to the subgenual anterior cingulate cortex(OFC/sgACC). Among women, higher HS scores were associated with smaller GMV in these areas while a positive correlation between GMV and HS scores was observed among men. These results remained significant after controlling for general intelligence, stress, anxiety and depression. Thus, this study suggested that structural differences between men and women are correlated to characteristic brain regions known to be involved in the PLS which is considered critical in stress regulation. PMID:25027617

The Rodent-versus-wild Snake Paradigm as a Model for Studying Anxiety- and Panic-like Behaviors: Face, Construct and Predictive Validities.

PubMed

Paschoalin-Maurin, Tatiana; Dos Anjos-Garcia, Tayllon; Falconi-Sobrinho, Luiz Luciano; de Freitas, Renato Leonardo; Coimbra, Jade Pissamiglio Cysne; Laure, Carlos Júlio; Coimbra, Norberto Cysne

2018-01-15

Using an innovative approach to study the neural bases of psychiatric disorders, this study investigated the behavioral, morphological and pharmacological bases of panic attack-induced responses in a prey-versus-coral snake paradigm. Mesocricetus auratus was chronically treated with intraperitoneal administration of the selective serotonin uptake inhibitor paroxetine or the gamma aminobutyric acid (GABA)/benzodiazepine receptor agonist alprazolam at three different doses and were then confronted with a venomous coral snake (Micrurus frontalis, Reptilia, Elapidae). The threatened rodents exhibited defensive attention, flat back approaches, defensive immobility, and escape defensive responses in the presence of the venomous snake, followed by increases in Fos protein in limbic structure neurons. Chronic administration of both paroxetine and alprazolam decreased these responses with morphological correlates between the panicolytic effect of both drugs administered at the highest dose and decreases in Fos protein-immunolabeled perikarya found in the amygdaloid complex, hypothalamus and periaqueductal gray matter columns, which are structures that make up the encephalic aversion system. These findings provide face, construct and predictive validities of this new experimental model of anxiety- and panic attack-like behavioral responses displayed by threatened prey confronted with venomous coral snakes. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

How demanding is the brain on a reversal task under day and night conditions?

PubMed

Arias, N; Fidalgo, C; Méndez, M; Arias, J L

2015-07-23

Reversal learning has been studied as the process of learning to inhibit previously rewarded actions. These behavioral studies are usually performed during the day, when animals are in their daily period rest. However, how day or night affects spatial reversal learning and the brain regions involved in the learning process are still unknown. We conducted two experiments using the Morris Water Maze under different light-conditions: naïve group (CN, n=8), day group (DY, n=8), control DY group (CDY, n=8) night group (NG, n=8), and control NG group (CNG, n=7). Distance covered, velocity and latencies to reach the platform were examined. After completing these tasks, cytochrome c-oxidase activity (CO) in several brain limbic system structures was compared between groups. There were no behavioral differences in the time of day when the animals were trained. However, the metabolic brain consumption was higher in rats trained in the day condition. This CO increase was supported by the prefrontal cortex, thalamus, dorsal and ventral striatum, hippocampus and entorhinal cortex, revealing their role in the performance of the spatial reversal learning task. Finally, the orbitofrontal cortex has been revealed as a key structure in reversal learning execution. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A semi-automated algorithm for hypothalamus volumetry in 3 Tesla magnetic resonance images.

PubMed

Wolff, Julia; Schindler, Stephanie; Lucas, Christian; Binninger, Anne-Sophie; Weinrich, Luise; Schreiber, Jan; Hegerl, Ulrich; Möller, Harald E; Leitzke, Marco; Geyer, Stefan; Schönknecht, Peter

2018-07-30

The hypothalamus, a small diencephalic gray matter structure, is part of the limbic system. Volumetric changes of this structure occur in psychiatric diseases, therefore there is increasing interest in precise volumetry. Based on our detailed volumetry algorithm for 7 Tesla magnetic resonance imaging (MRI), we developed a method for 3 Tesla MRI, adopting anatomical landmarks and work in triplanar view. We overlaid T1-weighted MR images with gray matter-tissue probability maps to combine anatomical information with tissue class segmentation. Then, we outlined regions of interest (ROIs) that covered potential hypothalamus voxels. Within these ROIs, seed growing technique helped define the hypothalamic volume using gray matter probabilities from the tissue probability maps. This yielded a semi-automated method with short processing times of 20-40 min per hypothalamus. In the MRIs of ten subjects, reliabilities were determined as intraclass correlations (ICC) and volume overlaps in percent. Three raters achieved very good intra-rater reliabilities (ICC 0.82-0.97) and good inter-rater reliabilities (ICC 0.78 and 0.82). Overlaps of intra- and inter-rater runs were very good (≥ 89.7%). We present a fast, semi-automated method for in vivo hypothalamus volumetry in 3 Tesla MRI. Copyright © 2018 Elsevier B.V. All rights reserved.

EEG Spectral Dynamics of Video Commercials: Impact of the Narrative on the Branding Product Preference

PubMed Central

Wang, Regina W. Y.; Chang, Yu-Ching; Chuang, Shang-Wen

2016-01-01

Neuromarketing has become popular and received a lot of attention. The quality of video commercials and the product information they convey to consumers is a hotly debated topic among advertising agencies and product advertisers. This study explored the impact of advertising narrative and the frequency of branding product exposures on the preference for the commercial and the branding product. We performed electroencephalography (EEG) experiments on 30 subjects while they watched video commercials. The behavioral data indicated that commercials with a structured narrative and containing multiple exposures of the branding products had a positive impact on the preference for the commercial and the branding product. The EEG spectral dynamics showed that the narratives of video commercials resulted in higher theta power of the left frontal, bilateral occipital region, and higher gamma power of the limbic system. The narratives also induced significant cognitive integration-related beta and gamma power of the bilateral temporal regions and the parietal region. It is worth noting that the video commercials with a single exposure of the branding products would be indicators of attention. These new findings suggest that the presence of a narrative structure in video commercials has a critical impact on the preference for branding products. PMID:27819348

Does the use of hormonal contraceptives cause microstructural changes in cerebral white matter? Preliminary results of a DTI and tractography study.

PubMed

De Bondt, Timo; Van Hecke, Wim; Veraart, Jelle; Leemans, Alexander; Sijbers, Jan; Sunaert, Stefan; Jacquemyn, Yves; Parizel, Paul M

2013-01-01

To evaluate the effect of monophasic combined oral contraceptive pill (COCP) and menstrual cycle phase in healthy young women on white matter (WM) organization using diffusion tensor imaging (DTI). Thirty young women were included in the study; 15 women used COCP and 15 women had a natural cycle. All subjects underwent DTI magnetic resonance imaging during the follicular and luteal phase of their cycle, or in different COCP cycle phases. DTI parameters were obtained in different WM structures by performing diffusion tensor fibre tractography. Fractional anisotropy and mean diffusivity were calculated for different WM structures. Hormonal plasma concentrations were measured in peripheral venous blood samples and correlated with the DTI findings. We found a significant difference in mean diffusivity in the fornix between the COCP and the natural cycle group. Mean diffusivity values in the fornix were negatively correlated with luteinizing hormone and estradiol blood concentrations. An important part in the limbic system, the fornix, regulates emotional processes. Differences in diffusion parameters in the fornix may contribute to behavioural alternations related to COCP use. This finding also suggests that the use of oral contraceptives needs to be taken into account when designing DTI group studies.

EEG Spectral Dynamics of Video Commercials: Impact of the Narrative on the Branding Product Preference.

PubMed

Wang, Regina W Y; Chang, Yu-Ching; Chuang, Shang-Wen

2016-11-07

Neuromarketing has become popular and received a lot of attention. The quality of video commercials and the product information they convey to consumers is a hotly debated topic among advertising agencies and product advertisers. This study explored the impact of advertising narrative and the frequency of branding product exposures on the preference for the commercial and the branding product. We performed electroencephalography (EEG) experiments on 30 subjects while they watched video commercials. The behavioral data indicated that commercials with a structured narrative and containing multiple exposures of the branding products had a positive impact on the preference for the commercial and the branding product. The EEG spectral dynamics showed that the narratives of video commercials resulted in higher theta power of the left frontal, bilateral occipital region, and higher gamma power of the limbic system. The narratives also induced significant cognitive integration-related beta and gamma power of the bilateral temporal regions and the parietal region. It is worth noting that the video commercials with a single exposure of the branding products would be indicators of attention. These new findings suggest that the presence of a narrative structure in video commercials has a critical impact on the preference for branding products.

Role of nitric oxide in pheromone-mediated intraspecific communication in mice.

PubMed

Agustín-Pavón, Carmen; Martínez-Ricós, Joana; Martínez-García, Fernando; Lanuza, Enrique

2009-12-07

Nitric oxide is known to take part in the control of sexual and agonistic behaviours. This is usually attributed to its role in neural transmission in the hypothalamus and other structures of the limbic system. However, socio-sexual behaviours in rodents are mainly directed by chemical signals detected by the vomeronasal system, and nitric oxide is abundant in key structures along the vomeronasal pathway. Thus, here we check whether pharmacological treatments interfering with nitrergic transmission could affect socio-sexual behaviour by impairing the processing of chemical signals. Treatment with an inhibitor of nitric oxide synthesis (Nomega-Nitro-l-arginine methyl ester hydrochloride, L-NAME, 100mg/kg) blocks the innate preference displayed by female mice for sexual pheromones contained in male-soiled bedding, with a lower dose of the drug (50mg/kg) having no effect. Animals treated with the high dose of L-NAME show no reduction of olfactory discrimination of male urine in a habituation-dishabituation test, thus suggesting that the effect of the drug on the preference for male pheromones is not due to an inability to detect male urine. Alternatively, it may result from an alteration in processing the reinforcing value of pheromones as sexual signals. These results add a new piece of evidence to our understanding of the neurochemistry of intraspecific chemical communication in rodents, and suggest that the role of nitric oxide in socio-sexual behaviours should be re-evaluated taking into account the involvement of this neuromodulator in the processing of chemical signals.

Function and Dysfunction of Prefrontal Brain Circuitry in Alcoholic Korsakoff’s Syndrome

PubMed Central

Oscar-Berman, Marlene

2013-01-01

The signature symptom of alcohol-induced persisting amnestic disorder, more commonly referred to as alcoholic Korsakoff’s syndrome (KS), is anterograde amnesia, or memory loss for recent events, and until the mid 20th Century, the putative brain damage was considered to be in diencephalic and medial temporal lobe structures. Overall intelligence, as measured by standardized IQ tests, usually remains intact. Preservation of IQ occurs because memories formed before the onset of prolonged heavy drinking — the types of information and abilities tapped by intelligence tests — remain relatively well preserved compared with memories recently acquired. However, clinical and experimental evidence has shown that neurobehavioral dysfunction in alcoholic patients with KS does include nonmnemonic abilities, and further brain damage involves extensive frontal and limbic circuitries. Among the abnormalities are confabulation, disruption of elements of executive functioning and cognitive control, and emotional impairments. Here, we discuss the relationship between neurobehavioral impairments in KS and alcoholism-related brain damage. More specifically, we examine the role of damage to prefrontal brain systems in the neuropsychological profile of alcoholic KS. PMID:22538385

Ultra-slow mechanical stimulation of olfactory epithelium modulates consciousness by slowing cerebral rhythms in humans.

PubMed

Piarulli, A; Zaccaro, A; Laurino, M; Menicucci, D; De Vito, A; Bruschini, L; Berrettini, S; Bergamasco, M; Laureys, S; Gemignani, A

2018-04-26

The coupling between respiration and neural activity within olfactory areas and hippocampus has recently been unambiguously demonstrated, its neurophysiological basis sustained by the well-assessed mechanical sensitivity of the olfactory epithelium. We herein hypothesize that this coupling reverberates to the whole brain, possibly modulating the subject's behavior and state of consciousness. The olfactory epithelium of 12 healthy subjects was stimulated with periodical odorless air-delivery (frequency 0.05 Hz, 8 s on, 12 off). Cortical electrical activity (High Density-EEG) and perceived state of consciousness have been studied. The stimulation induced i) an enhancement of delta-theta EEG activity over the whole cortex mainly involving the Limbic System and Default Mode Network structures, ii) a reversal of the overall information flow directionality from wake-like postero-anterior to NREM sleep-like antero-posterior, iii) the perception of having experienced an Altered State of Consciousness. These findings could shed further light via a neurophenomenological approach on the links between respiration, cerebral activity and subjective experience, suggesting a plausible neurophysiological basis for interpreting altered states of consciousness induced by respiration-based meditative practices.

Brain evolution relating to family, play, and the separation call.

PubMed

MacLean, P D

1985-04-01

Mammals stem from the mammal-like reptiles (therapsids) that were widely prevalent in Pangaea 250 million years ago. In the evolutionary transition from reptiles to mammals, three key developments were (1) nursing, in conjunction with maternal care; (2) audiovocal communication for maintaining maternal-offspring contact; and (3) play. The separation call perhaps ranks as the earliest and most basic mammalian vocalization, while play may have functioned originally to promote harmony in the nest. How did such family related behavior develop? In its evolution, the forebrain of advanced mammals has expanded as a triune structure that anatomically and chemically reflects ancestral commonalities with reptiles, early mammals, and late mammals. Recent findings suggest that the development of the behavioral triad in question may have depended on the evolution of the thalamocingulate division of the limbic system, a derivative from early mammals. The thalamocingulate division (which has no distinctive counterpart in the reptilian brain) is, in turn, geared in with the prefrontal neocortex that, in human beings, may be inferred to play a key role in familial acculturation.

Preserved and Impaired Emotional Memory in Alzheimer’s Disease

PubMed Central

Klein-Koerkamp, Yanica; Baciu, Monica; Hot, Pascal

2012-01-01

Patients with early atrophy of both limbic structures involved in memory and emotion processing in Alzheimer’s disease (AD) provide a unique clinical population for investigating how emotion is able to modulate retention processes. This review focuses on the emotional enhancement effect (EEE), defined as the improvement of memory for emotional events compared with neutral ones. The assessment of the EEE for different memory systems in AD suggests that the EEE could be preserved under specific retrieval instructions. The first part of this review examines these data in light of compelling evidence that the amygdala can modulate processes of hippocampus-dependent memory. We argue that the EEE could be a useful paradigm to reduce impairment in episodic memory tasks. In the second part, we discuss theoretical consequences of the findings in favor of an EEE, according to which a compensatory mechanism in patients with AD solicits greater amygdala functioning or additional networks, even when amygdala atrophy is present. These considerations emphasize the relevance of investigating patients with AD to understand the relationship between emotion and memory processes. PMID:23049516

An expanded view of energy homeostasis: Neural integration of metabolic, cognitive, and emotional drives to eat

PubMed Central

Shin, Andrew C.; Zheng, Huiyuan; Berthoud, Hans-Rudolf

2009-01-01

The traditional view of neural regulation of body energy homeostasis focuses on internal feedback signals integrated in the hypothalamus and brainstem and in turn leading to balanced activation of behavioral, autonomic, and endocrine effector pathways leading to changes in food intake and energy expenditure. Recent observations have demonstrated that many of these internal signals encoding energy status have much wider effects on the brain, particularly sensory and cortico-limbic systems that process information from the outside world by detecting and interpreting food cues, forming, storing, and recalling representations of experience with food, and assigning hedonic and motivational value to conditioned and unconditioned food stimuli. Thus, part of the metabolic feedback from the internal milieu regulates food intake and energy balance by acting on extrahypothalamic structures, leading to an expanded view of neural control of energy homeostasis taking into account the need to adapt to changing conditions in the environment. The realization that metabolic signals act directly on these non-traditional targets of body energy homeostasis brings opportunities for novel drug targets for the fight against obesity and eating disorders. PMID:19419661

The von Economo neurons in fronto-insular and anterior cingulate cortex

PubMed Central

Allman, John M.; Tetreault, Nicole A.; Hakeem, Atiya Y.; Manaye, Kebreten F.; Semendeferi, Katerina; Erwin, Joseph M.; Park, Soyoung; Goubert, Virginie; Hof, Patrick R.

2011-01-01

The von Economo neurons (VENs) are large bipolar neurons located in fronto-insular cortex (FI) and anterior limbic area (LA) in great apes and humans but not in other primates. Our stereological counts of VENs in FI and LA show them to be more numerous in humans than in apes. In humans, small numbers of VENs appear the 36th week post conception, with numbers increasing during the first eight months after birth. There are significantly more VENs in the right hemisphere in postnatal brains; this may be related to asymmetries in the autonomic nervous system. VENs are also present in elephants and whales and may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI and LA to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of fronto-temporal dementia implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging. PMID:21534993

Distorted images of one's own body activates the prefrontal cortex and limbic/paralimbic system in young women: a functional magnetic resonance imaging study.

PubMed

Kurosaki, Mitsuhaya; Shirao, Naoko; Yamashita, Hidehisa; Okamoto, Yasumasa; Yamawaki, Shigeto

2006-02-15

Our aim was to study the gender differences in brain activation upon viewing visual stimuli of distorted images of one's own body. We performed functional magnetic resonance imaging on 11 healthy young men and 11 healthy young women using the "body image tasks" which consisted of fat, real, and thin shapes of the subject's own body. Comparison of the brain activation upon performing the fat-image task versus real-image task showed significant activation of the bilateral prefrontal cortex and left parahippocampal area including the amygdala in the women, and significant activation of the right occipital lobe including the primary and secondary visual cortices in the men. Comparison of brain activation upon performing the thin-image task versus real-image task showed significant activation of the left prefrontal cortex, left limbic area including the cingulate gyrus and paralimbic area including the insula in women, and significant activation of the occipital lobe including the left primary and secondary visual cortices in men. These results suggest that women tend to perceive distorted images of their own bodies by complex cognitive processing of emotion, whereas men tend to perceive distorted images of their own bodies by object visual processing and spatial visual processing.

Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy associated with VGKC-complex antibodies.

PubMed

Suleiman, Jehan; Brenner, Tanja; Gill, Deepak; Troedson, Christopher; Sinclair, Adriane J; Brilot, Fabienne; Vincent, Angela; Lang, Bethan; Dale, Russell C

2011-11-01

Autoantibodies that bind to voltage-gated potassium-channel complex proteins (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis presenting with cognitive impairment and seizures. Recently, VGKC-complex antibodies have been described in a few children with limbic encephalitis, and children with unexplained encephalitis presenting with status epilepticus. We report a case of infantile-onset epileptic spasms and developmental delay compatible with epileptic encephalopathy. Our patient was a female infant, aged 4 months at presentation. She had evidence of immune activation in the central nervous system with elevated cerebrospinal fluid neopterin and mirrored oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex antibodies were elevated (201 pmol/L, normal<100), but extended antibody testing, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein 2 (CASPR2), was negative. The patient showed a partial response to steroid treatment, which was started late in the disease course. On review at 13 months of age, her development was consistent with an age of 5 to 6 months. These results suggest that VGKC-complex antibodies might represent a marker of immune therapy responsiveness in a subgroup of patients with infantile epileptic encephalopathy. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

Negative Urgency Mediates the Relationship between Amygdala and Orbitofrontal Cortex Activation to Negative Emotional Stimuli and General Risk-Taking

PubMed Central

Cyders, Melissa A.; Dzemidzic, Mario; Eiler, William J.; Coskunpinar, Ayca; Karyadi, Kenny A.; Kareken, David A.

2015-01-01

The tendency toward impulsive behavior under emotional duress (negative and positive urgency) predicts a wide range of maladaptive risk-taking and behavioral disorders. However, it remains unclear how urgency relates to limbic system activity as induced from emotional provocation. This study used functional magnetic resonance imaging to examine the relationship between brain responses to visual emotional stimuli and urgency traits. Twenty-seven social drinkers (mean age = 25.2, 14 males) viewed negative (Neg), neutral (Neu), and positive (Pos) images during 6 fMRI scans. Brain activation was extracted from a priori limbic regions previously identified in studies of emotional provocation. The right posterior orbitofrontal cortex (OFC) and left amygdala were activated in the [Neg>Neu] contrast, whereas the left posterior OFC was activated in the [Pos>Neu] contrast. Negative urgency was related to the right lateral OFC (r = 0.43, P = 0.03) and the left amygdala (r = 0.39, P = 0.04) [Neg>Neu] activation. Negative urgency also mediated the relationship between [Neg>Neu] activation and general risk-taking (regression weights = 3.42 for right OFC and 2.75 for the left amygdala). Emotional cue-induced activation in right lateral OFC and left amygdala might relate to emotion-based risk-taking through negative urgency. PMID:24904065

Acupuncture analgesia involves modulation of pain-induced gamma oscillations and cortical network connectivity.

PubMed

Hauck, Michael; Schröder, Sven; Meyer-Hamme, Gesa; Lorenz, Jürgen; Friedrichs, Sunja; Nolte, Guido; Gerloff, Christian; Engel, Andreas K

2017-11-24

Recent studies support the view that cortical sensory, limbic and executive networks and the autonomic nervous system might interact in distinct manners under the influence of acupuncture to modulate pain. We performed a double-blind crossover design study to investigate subjective ratings, EEG and ECG following experimental laser pain under the influence of sham and verum acupuncture in 26 healthy volunteers. We analyzed neuronal oscillations and inter-regional coherence in the gamma band of 128-channel-EEG recordings as well as heart rate variability (HRV) on two experimental days. Pain ratings and pain-induced gamma oscillations together with vagally-mediated power in the high-frequency bandwidth (vmHF) of HRV decreased significantly stronger during verum than sham acupuncture. Gamma oscillations were localized in the prefrontal cortex (PFC), mid-cingulate cortex (MCC), primary somatosensory cortex and insula. Reductions of pain ratings and vmHF-power were significantly correlated with increase of connectivity between the insula and MCC. In contrast, connectivity between left and right PFC and between PFC and insula correlated positively with vmHF-power without a relationship to acupuncture analgesia. Overall, these findings highlight the influence of the insula in integrating activity in limbic-saliency networks with vagally mediated homeostatic control to mediate antinociception under the influence of acupuncture.

Aromatherapy: mythical, magical, or medicinal?

PubMed

Thomas, Deborah V

2002-10-01

Aromatherapy, a branch of herbology, is one of the fastest growing therapies in the world today. Historically, essential oils are best used in the form of massage or bath oils or inhalations. Frequently, it is reported that aromatherapy leaves one feeling uplifted, stimulated, invigorated, or rejuvenated, depending on the oil used. When inhaled, the various aromas penetrate the bloodstream via the lungs causing physiologic changes. In turn, the limbic system, which controls our emotions and memories, is affected. Some consider aromatherapy as mystical or magical; others, however, are attempting to validate empirically this ancient therapy as medicinal.

Clinico-pathological correlation in adenylate kinase 5 autoimmune limbic encephalitis

PubMed Central

Ng, Adeline S.L.; Kramer, Joel; Centurion, Alejandro; Dalmau, Josep; Huang, Eric; Cotter, Jennifer A.; Geschwind, Michael D.

2016-01-01

Autoantibodies associated with autoimmune limbic encephalitis (ALE) have been well-characterized, with intracellular neuronal antibodies being less responsive to immunotherapy than antibodies to cell surface antigens. Adenylate kinase 5 (AK5) is a nucleoside monophosphate kinase vital for neuronal-specific metabolism and is located intracellularly in the cytosol and expressed exclusively in the brain. Antibodies to AK5 had been previously identified but were not known to be associated with human disease prior to the report of two patients with AK5-related ALE (Tuzun et al., 2007). We present the complete clinical picture for one of these patients and the first reported neuropathology for AK5 ALE. PMID:26439959

Case Studies Illustrating Focal Alzheimer's, Fluent Aphasia, Late-Onset Memory Loss, and Rapid Dementia.

PubMed

Camsari, Gamze Balci; Murray, Melissa E; Graff-Radford, Neill R

2016-08-01

Many dementia subtypes have more shared signs and symptoms than defining ones. We review 8 cases with 4 overlapping syndromes and demonstrate how to distinguish the cases. These include focal cortical presentations of Alzheimer's disease (AD; posterior cortical atrophy and corticobasal syndrome [CBS]), fluent aphasia (semantic dementia and logopenic aphasia), late-onset slowly progressive dementia (hippocampal sclerosis and limbic predominant AD) and rapidly progressive dementia (Creutzfeldt-Jakob disease and limbic encephalitis). Recognizing the different syndromes can help the clinician to improve their diagnostic skills, leading to improved patient outcomes by early and accurate diagnosis, prompt treatment, and appropriate counseling and guidance. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced serotonin receptor subtypes in a limbic and a neocortical region in autism.

PubMed

Oblak, Adrian; Gibbs, Terrell T; Blatt, Gene J

2013-12-01

Autism is a behaviorally defined, neurological disorder with symptom onset before the age of 3. Abnormalities in social-emotional behaviors are a core deficit in autism, and are characterized by impaired reciprocal-social interaction, lack of facial expressions, and the inability to recognize familiar faces. The posterior cingulate cortex (PCC) and fusiform gyrus (FG) are two regions within an extensive limbic-cortical network that contribute to social-emotional behaviors. Evidence indicates that changes in brains of individuals with autism begin prenatally. Serotonin (5-HT) is one of the earliest expressed neurotransmitters, and plays an important role in synaptogenesis, neurite outgrowth, and neuronal migration. Abnormalities in 5-HT systems have been implicated in several psychiatric disorders, including autism, as evidenced by immunology, imaging, genetics, pharmacotherapy, and neuropathology. Although information is known regarding peripheral 5-HT in autism, there is emerging evidence that 5-HT systems in the central nervous system, including various 5-HT receptor subtypes and transporters, are affected in autism. The present study demonstrated significant reductions in 5-HT1A receptor-binding density in superficial and deep layers of the PCC and FG, and in the density of 5-HT(2A) receptors in superficial layers of the PCC and FG. A significant reduction in the density of serotonin transporters (5-HTT) was also found in the deep layers of the FG, but normal levels were demonstrated in both layers of the PCC and superficial layers of the FG. This study provides potential substrates for decreased 5-HT modulation/innervation in the autism brain, and implicate two 5-HT receptor subtypes as potential neuromarkers for novel or existing pharmacotherapies. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

The Neuroendocrine System and Stress, Emotions, Thoughts and Feelings**

PubMed Central

Vaillant, George E.

2011-01-01

The philosophy of mind is intimately connected with the philosophy of action. Therefore, concepts like free will, motivation, emotions (especially positive emotions), and also the ethical issues related to these concepts are of abiding interest. However, the concepts of consciousness and free will are usually discussed solely in linguistic, ideational and cognitive (i.e. “left brain”) terms. Admittedly, consciousness requires language and the left-brain, but the aphasic right brain is equally conscious; however, what it “hears” are more likely to be music and emotions. Joy can be as conscious as the conscious motivation produced by the left-brain reading a sign that says, “Danger mines!!” However, look in the index of a Western textbook of psychology, psychiatry or philosophy for positive emotions located in the limbic system. Notice how discussion of positive spiritual/emotional issues in consciousness and motivation are scrupulously ignored. For example, the popular notions of “love” being either Eros (raw, amoral instinct) or agape (noble, non-specific valuing of all other people) miss the motivational forest for the trees. Neither Eros (hypothalamic) nor agape (cortical) has a fraction of the power to relieve stress as attachment (limbic love), yet until the 1950s attachment was neither appreciated nor discussed by academic minds. This paper will point out that the prosocial, “spiritual” positive emotions like hope, faith, forgiveness, joy, compassion and gratitude are extremely important in the relief of stress and in regulation of the neuroendocrine system, protecting us against stress. The experimental work reviewed by Antonio Damasio and Barbara Fredrickson, and the clinical example of Alcoholics Anonymous, will be used to illustrate these points. PMID:21694965

Pretherapeutic Functional Imaging Allows Prediction of Head Tremor Arrest After Thalamotomy for Essential Tremor: The Role of Altered Interconnectivity Between Thalamolimbic and Supplementary Motor Circuits.

PubMed

Tuleasca, Constantin; Régis, Jean; Najdenovska, Elena; Witjas, Tatiana; Girard, Nadine; Champoudry, Jérôme; Faouzi, Mohamed; Thiran, Jean-Philippe; Cuadra, Meritxell Bach; Levivier, Marc; Van De Ville, Dimitri

2018-04-01

To correlate pretherapeutic resting-state functional magnetic resonance imaging (rs-fMRI) measures with pretherapeutic head tremor presence and/or further improvement 1 year after stereotactic radiosurgical thalamotomy (SRS-T) for essential tremor (ET). We prospectively collected head tremor scores (range, 0-3) and rs-fMRI data for a cohort of 17 consecutive ET patients in pretherapeutic and 1 year after SRS-T states. We additionally acquired rs-fMRI data for a healthy control (HC) group (n = 12). Group-level independent component analysis (n = 17 for pretherapeutic rs-fMRI) was applied to decompose neuroimaging data into 20 large-scale brain networks using a standard approach. Through spatial regression, we projected 1 year after SRS-T and HC rs-fMRI time points, on the same 20 brain networks. Pretherapeutic interconnectivity (IC) strength between the network including bilateral thalamus and limbic system with left supplementary motor area predicted head tremor improvement at 1 year after SRS-T (family-wise corrected P < 0.001, cluster size K c  = 146). For the statistically significant cluster, IC strength was strongest in HCs (mean, 4.6; median, 3.8) compared with pre- (mean, 0.1; median, 0.2) or posttherapeutic (mean, -0.2; median, 0.09) states. Baseline measures of IC between bilateral thalamus and limbic system with left supplementary motor area may predict head tremor arrest after thalamotomy. However, procedures such as SRS-T, for this particular clinical feature, do not align patients to HCs in terms of functional brain connectivity. We postulate that supplementary motor area is modulating head tremor appearance, by abnormal connectivity with the thalamolimbic system. Copyright © 2018 Elsevier Inc. All rights reserved.

Altered structural network architecture is predictive of the presence of psychotic symptoms in patients with 22q11.2 deletion syndrome.

PubMed

Padula, Maria C; Scariati, Elisa; Schaer, Marie; Sandini, Corrado; Ottet, Marie Christine; Schneider, Maude; Van De Ville, Dimitri; Eliez, Stephan

2017-01-01

22q11.2 deletion syndrome (22q11DS) represents a homogeneous model of schizophrenia particularly suitable for the search of neural biomarkers of psychosis. Impairments in structural connectivity related to the presence of psychotic symptoms have been reported in patients with 22q11DS. However, the relationships between connectivity changes in patients with different symptomatic profiles are still largely unknown and warrant further investigations. In this study, we used structural connectivity to discriminate patients with 22q11DS with ( N  = 31) and without ( N  = 31) attenuated positive psychotic symptoms. Different structural connectivity measures were used, including the number of streamlines connecting pairs of brain regions, graph theoretical measures, and diffusion measures. We used univariate group comparisons as well as predictive multivariate approaches. The univariate comparison of connectivity measures between patients with or without attenuated positive psychotic symptoms did not give significant results. However, the multivariate prediction revealed that altered structural network architecture discriminates patient subtypes (accuracy = 67.7%). Among the regions contributing to the classification we found the anterior cingulate cortex, which is known to be associated to the presence of psychotic symptoms in patients with 22q11DS. Furthermore, a significant discrimination (accuracy = 64%) was obtained with fractional anisotropy and radial diffusivity in the left inferior longitudinal fasciculus and the right cingulate gyrus. Our results point to alterations in structural network architecture and white matter microstructure in patients with 22q11DS with attenuated positive symptoms, mainly involving connections of the limbic system. These alterations may therefore represent a potential biomarker for an increased risk of psychosis that should be further tested in longitudinal studies.

The frontoparietal control system: A central role in mental health

PubMed Central

Cole, Michael W.; Repovs, Grega; Anticevic, Alan

2014-01-01

Recent findings suggest the existence of a frontoparietal control system consisting of ‘flexible hubs’ that regulate distributed systems (e.g., visual, limbic, motor) according to current task goals. A growing number of studies are reporting alterations of this control system across a striking range of mental diseases. We suggest this may reflect a critical role for the control system in promoting and maintaining mental health. Specifically, we propose that this system implements feedback control to regulate symptoms as they arise (e.g., excessive anxiety reduced via regulation of amygdala), such that an intact control system is protective against a variety of mental illnesses. Consistent with this possibility, recent results indicate that several major mental illnesses involve altered brain-wide connectivity of the control system, likely altering its ability to regulate symptoms. These results suggest that this ‘immune system of the mind’ may be an especially important target for future basic and clinical research. PMID:24622818

Centromedian-parafascicular deep brain stimulation induces differential functional inhibition of the motor, associative, and limbic circuits in large animals.

PubMed

Kim, Joo Pyung; Min, Hoon-Ki; Knight, Emily J; Duffy, Penelope S; Abulseoud, Osama A; Marsh, Michael P; Kelsey, Katherine; Blaha, Charles D; Bennet, Kevin E; Frye, Mark A; Lee, Kendall H

2013-12-15

Deep brain stimulation (DBS) of the centromedian-parafascicular (CM-Pf) thalamic nuclei has been considered an option for treating Tourette syndrome. Using a large animal DBS model, this study was designed to explore the network effects of CM-Pf DBS. The combination of DBS and functional magnetic resonance imaging is a powerful means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network in vivo. With a within-subjects design, we tested the proportional effects of CM and Pf DBS by manipulating current spread and varying stimulation contacts in healthy pigs (n = 5). Our results suggests that CM-Pf DBS has an inhibitory modulating effect in areas that have been suggested as contributing to impaired sensory-motor and emotional processing. The results also help to define the differential neural circuitry effects of the CM and Pf with evidence of prominent sensorimotor/associative effects for CM DBS and prominent limbic/associative effects for Pf DBS. Our results support the notion that stimulation of deep brain structures, such as the CM-Pf, modulates multiple networks with cortical effects. The networks affected by CM-Pf stimulation in this study reinforce the conceptualization of Tourette syndrome as a condition with psychiatric and motor symptoms and of CM-Pf DBS as a potentially effective tool for treating both types of symptoms. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The changing landscape of functional brain networks for face processing in typical development.

PubMed

Joseph, Jane E; Swearingen, Joshua E; Clark, Jonathan D; Benca, Chelsie E; Collins, Heather R; Corbly, Christine R; Gathers, Ann D; Bhatt, Ramesh S

2012-11-15

Greater expertise for faces in adults than in children may be achieved by a dynamic interplay of functional segregation and integration of brain regions throughout development. The present study examined developmental changes in face network functional connectivity in children (5-12 years) and adults (18-43 years) during face-viewing using a graph-theory approach. A face-specific developmental change involved connectivity of the right occipital face area. During childhood, this node increased in strength and within-module clustering based on positive connectivity. These changes reflect an important role of the ROFA in segregation of function during childhood. In addition, strength and diversity of connections within a module that included primary visual areas (left and right calcarine) and limbic regions (left hippocampus and right inferior orbitofrontal cortex) increased from childhood to adulthood, reflecting increased visuo-limbic integration. This integration was pronounced for faces but also emerged for natural objects. Taken together, the primary face-specific developmental changes involved segregation of a posterior visual module during childhood, possibly implicated in early stage perceptual face processing, and greater integration of visuo-limbic connections from childhood to adulthood, which may reflect processing related to development of perceptual expertise for individuation of faces and other visually homogenous categories. Copyright © 2012 Elsevier Inc. All rights reserved.