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Sample records for limbic brain areas

  1. 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

  2. Functional connectivity among limbic brain areas: differential effects of incubation temperature and gonadal sex in the leopard gecko, Eublepharis macularius.

    PubMed

    Sakata, J T; Coomber, P; Gonzalez-Lima, F; Crews, D

    2000-03-01

    The neural basis of individual differences in behavior has been studied primarily by analyzing the properties of specific neural areas. However, because of the organization of the nervous system, it is also plausible that differences in behavior are mediated by differences in the interactivity or functional connectivity among brain nuclei in particular neural circuits. In the leopard gecko, Eublepharis macularius, the temperature of the egg during incubation not only determines gonadal sex, but also shapes the sociosexual behaviors, reproductive physiology, and hormone sensitivity of adult animals. In this study the effects of both incubation temperature and gonadal sex on functional connectivity among limbic brain areas were examined. Functional connectivity was assessed by analyzing covariance patterns in metabolic capacity, as revealed by quantitative cytochrome oxidase histochemistry. It was hypothesized that incubation temperature and gonadal sex affect the propensity to display aggressive or sexual behaviors by altering the functional connectivity within relevant neural circuits. The correlations of metabolic capacity between the anterior hypothalamus and both the septum and preoptic area were significant only in relatively aggressive individuals, suggesting that these circuits may regulate the phenotypic variation in aggressiveness caused by incubation temperature. The correlations between the ventromedial hypothalamus and both the dorsal ventricular ridge and septum were significant only in females, suggesting that these circuits may modulate female-typical sexual behaviors. Correlations among preoptic, hypothalamic and amygdalar areas tended to be distributed across both sexes, suggesting that there may be shared pathways underlying the expression of male-typical and female-typical behaviors. Copyright 2000 S. Karger AG, Basel

  3. 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

  4. Parental Deprivation Induces N-Methyl-D-Aspartate-Receptor Upregulation in Limbic Brain Areas of Octodon degus: Protective Role of the Maternal Call

    PubMed Central

    Ziabreva, Irina; Schnabel, Reinhild; Braun, Katharina

    2000-01-01

    An optimal coordination between parents and their offspring involves a sequence of reciprocal behaviors to ensure the adequate care of the young, which is critical for a healthy physical, emotional, and social development. Parental deprivation, particularly an impaired child-mother attachment, induces lasting changes in emotional as well as in cognitive capacities in later life. We assessed in the South American precocial species, Octodon degus, whether alterations of glutamatergic function of the limbic system induced by parental deprivation may be a neural correlate for such behavioral changes. Further, we analyzed whether the mother's voice can protect from separation-induced changes of brain function. Changes of N-methyl-D-aspartate (NMDA) receptor expression were examined in the following three groups of 2-week-old Octodon degus pups: (I) control animals who remained undisturbed with the family; (II) animals who were repeatedly separated from the family and individually placed in an unfamiliar environment for behavioral analysis (open field); and (III) animals who were treated like the group described under (lI) but were presented with maternal vocalizations during separation. Relative to those in the control group I, the animals in group II showed an upregulation of NMDA receptor density in the (a)anterior cingulate, prelimbic, infralimbic, and anterior insular cortices; (b)CA1/stratum radiatum; (c)CA1/stratum lacunosum moleculare and CA3/stratum radiatum; and (d)in the basomedial amygdaloid nucleus. Presentation of the maternal call during the separation period (group III) suppressed the separation-induced NMDA receptor upregulation in all regions. The results demonstrate that early life events can influence the expression of transmitter receptors and that maternal behavior, acting to control the pup's socio-emotional environment, is a key factor for regulating such developmental events. PMID:11486484

  5. Interactive effects of BDNF Val66Met genotype and trauma on limbic brain anatomy in childhood

    PubMed Central

    Marusak, Hilary A.; Kuruvadi, Nisha; Vila, Angela M.; Shattuck, David W.; Joshi, Shantanu H.; Joshi, Anand A.; Jella, Pavan K.; Thomason, Moriah E.

    2015-01-01

    Childhood trauma is a major precipitating factor in psychiatric disease. Emerging data suggest that stress susceptibility is genetically determined, and that risk is mediated by changes in limbic brain circuitry. There is a need to identify markers of disease vulnerability, and it is critical that these markers be investigated in childhood and adolescence, a time when neural networks are particularly malleable and when psychiatric disorders frequently emerge. In this preliminary study, we evaluated whether a common variant in the brain-derived neurotrophic factor (BDNF) gene (Val66Met; rs6265) interacts with childhood trauma to predict limbic gray matter volume in a sample of 55 youth high in sociodemographic risk. We found trauma-by-BDNF interactions in the right subcallosal area and right hippocampus, wherein BDNF-related gray matter changes were evident in youth without histories of trauma. In youth without trauma exposure, lower hippocampal volume was related to higher symptoms of anxiety. These data provide preliminary evidence for a contribution of a common BDNF gene variant to the neural correlates of childhood trauma among high-risk urban youth. Altered limbic structure in early life may lay the foundation for longer-term patterns of neural dysfunction, and hold implications for understanding the psychiatric and psychobiological consequences of traumatic stress on the developing brain. PMID:26286685

  6. Interactive effects of BDNF Val66Met genotype and trauma on limbic brain anatomy in childhood.

    PubMed

    Marusak, Hilary A; Kuruvadi, Nisha; Vila, Angela M; Shattuck, David W; Joshi, Shantanu H; Joshi, Anand A; Jella, Pavan K; Thomason, Moriah E

    2016-05-01

    Childhood trauma is a major precipitating factor in psychiatric disease. Emerging data suggest that stress susceptibility is genetically determined, and that risk is mediated by changes in limbic brain circuitry. There is a need to identify markers of disease vulnerability, and it is critical that these markers be investigated in childhood and adolescence, a time when neural networks are particularly malleable and when psychiatric disorders frequently emerge. In this preliminary study, we evaluated whether a common variant in the brain-derived neurotrophic factor (BDNF) gene (Val66Met; rs6265) interacts with childhood trauma to predict limbic gray matter volume in a sample of 55 youth high in sociodemographic risk. We found trauma-by-BDNF interactions in the right subcallosal area and right hippocampus, wherein BDNF-related gray matter changes were evident in youth without histories of trauma. In youth without trauma exposure, lower hippocampal volume was related to higher symptoms of anxiety. These data provide preliminary evidence for a contribution of a common BDNF gene variant to the neural correlates of childhood trauma among high-risk urban youth. Altered limbic structure in early life may lay the foundation for longer term patterns of neural dysfunction, and hold implications for understanding the psychiatric and psychobiological consequences of traumatic stress on the developing brain.

  7. 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

    2016-12-28

    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.

  8. Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas.

    PubMed

    Fortes, Paula Madeira; Albrechet-Souza, Lucas; Vasconcelos, Mailton; Ascoli, Bruna Maria; Menegolla, Ana Paula; de Almeida, Rosa Maria M

    2017-01-01

    Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

  9. Lost for emotion words: what motor and limbic brain activity reveals about autism and semantic theory.

    PubMed

    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. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  10. 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

  11. Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders

    PubMed Central

    Vadnie, Chelsea A.; Park, Jun Hyun; Abdel Gawad, Noha; Ho, Ada Man Choi; Hinton, David J.; Choi, Doo-Sup

    2014-01-01

    Peptides synthesized in endocrine cells in the gastrointestinal tract and neurons are traditionally considered regulators of metabolism, energy intake, and appetite. However, recent work has demonstrated that many of these peptides act on corticostriatal-limbic circuitry and, in turn, regulate addictive behaviors. Given that alcohol is a source of energy and an addictive substance, it is not surprising that increasing evidence supports a role for gut-brain peptides specifically in alcohol use disorders (AUD). In this review, we discuss the effects of several gut-brain peptides on alcohol-related behaviors and the potential mechanisms by which these gut-brain peptides may interfere with alcohol-induced changes in corticostriatal-limbic circuitry. This review provides a summary of current knowledge on gut-brain peptides focusing on five peptides: neurotensin, glucagon-like peptide 1, ghrelin, substance P, and neuropeptide Y. Our review will be helpful to develop novel therapeutic targets for AUD. PMID:25278825

  12. Perfluorooctane sulfonate (PFOS) exposure could modify the dopaminergic system in several limbic brain regions.

    PubMed

    Salgado, R; López-Doval, S; Pereiro, N; Lafuente, A

    2016-01-05

    Perfluorooctane sulfonate (PFOS) is the most representative of a rising class of persistent organic pollutants perfluorochemicals. In the present study, its neurotoxicity was examined using adult male rats orally treated with 0.5; 1.0; 3.0 and 6.0 mg of PFOS/kg/day for 28 days. At the end of the treatment, the dopamine concentration and its metabolism expressed like the ratio 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine and homovanillic acid (HVA)/dopamine were measured in the amygdala, prefrontal cortex and hippocampus. Gene and protein expression of the dopamine receptors D1 and D2 were also determined in these limbic areas. The obtained results suggest that: (1) PFOS can alter the dopamine system by modifying its neuronal activity and/or its D1 and D2 receptors in the studied brain regions; (2) the dopamine concentration and metabolism seem to be more sensitive against PFOS toxicity in the hippocampus than in the other analyzed brain areas; (3) the inhibited gene and protein expression of the D1 receptors induced by PFOS in the amygdala could be related to several changes in the HPA axis activity, and lastly; (4) the observed alterations on the dopamine system induced by PFOS could be a possible neurotoxicity mechanism of PFOS, leading to many neurological diseases.

  13. Brain tissue properties differentiate between motor and limbic basal ganglia circuits

    PubMed Central

    Accolla, Ettore A; Dukart, Juergen; Helms, Gunther; Weiskopf, Nikolaus; Kherif, Ferath; Lutti, Antoine; Chowdhury, Rumana; Hetzer, Stefan; Haynes, John-Dylan; Kühn, Andrea A; Draganski, Bogdan

    2014-01-01

    Despite advances in understanding basic organizational principles of the human basal ganglia, accurate in vivo assessment of their anatomical properties is essential to improve early diagnosis in disorders with corticosubcortical pathology and optimize target planning in deep brain stimulation. Main goal of this study was the detailed topological characterization of limbic, associative, and motor subdivisions of the subthalamic nucleus (STN) in relation to corresponding corticosubcortical circuits. To this aim, we used magnetic resonance imaging and investigated independently anatomical connectivity via white matter tracts next to brain tissue properties. On the basis of probabilistic diffusion tractography we identified STN subregions with predominantly motor, associative, and limbic connectivity. We then computed for each of the nonoverlapping STN subregions the covariance between local brain tissue properties and the rest of the brain using high-resolution maps of magnetization transfer (MT) saturation and longitudinal (R1) and transverse relaxation rate (R2*). The demonstrated spatial distribution pattern of covariance between brain tissue properties linked to myelin (R1 and MT) and iron (R2*) content clearly segregates between motor and limbic basal ganglia circuits. We interpret the demonstrated covariance pattern as evidence for shared tissue properties within a functional circuit, which is closely linked to its function. Our findings open new possibilities for investigation of changes in the established covariance pattern aiming at accurate diagnosis of basal ganglia disorders and prediction of treatment outcome. PMID:24777915

  14. Limbic Metabolic Abnormalities in Remote Traumatic Brain Injury and Correlation With Psychiatric Morbidity and Social Functioning

    PubMed Central

    Capizzano, Arístides A.; Jorge, Ricardo E.; Robinson, Robert G.

    2013-01-01

    The aim of this study was to investigate limbic metabolic abnormalities in remote traumatic brain injury (TBI) and their psychiatric correlates. Twenty patients and 13 age-matched comparison subjects received complete psychiatric evaluation and brain MRI and MR spectroscopy at 3 Tesla. Patients had reduced NAA to creatine ratio in the left hippocampus relative to comparison subjects (mean=1.3 [SD=0.21] compared with mean=1.55 [SD=0.21]; F=10.73, df=1, 30, p=0.003), which correlated with the Social Functioning Examination scores (rs=−0.502, p=0.034). Furthermore, patients with mood disorders had reduced NAA to creatine ratio in the left cingulate relative to patients without mood disorders (1.47 compared with 1.68; F=3.393, df=3, 19, p=0.044). Remote TBI displays limbic metabolic abnormalities, which correlate to social outcome and psychiatric status. PMID:21037120

  15. Limbic, associative, and motor territories within the targets for deep brain stimulation: potential clinical implications.

    PubMed

    Sudhyadhom, Atchar; Bova, Frank J; Foote, Kelly D; Rosado, Christian A; Kirsch-Darrow, Lindsey; Okun, Michael S

    2007-07-01

    The use of deep brain stimulation (DBS) has recently been expanding for the treatment of many neurologic disorders such as Parkinson disease, dystonia, essential tremor, Tourette's syndrome, cluster headache, epilepsy, depression, and obsessive compulsive disorder. The target structures for DBS include specific segregated territories within limbic, associative, or motor regions of very small subnuclei. In this review, we summarize current clinical techniques for DBS, the cognitive/mood/motor outcomes, and the relevant neuroanatomy with respect to functional territories within specific brain targets. Future development of new techniques and technology that may include a more direct visualization of "motor" territories within target structures may prove useful for avoiding side effects that may result from stimulation of associative and limbic regions. Alternatively, newer procedures may choose and specifically target non-motor territories for chronic electrical stimulation.

  16. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

    SciTech Connect

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Telang, F.; Fowler, J.S.; Pradhan, K.; Jayne, M.; Logan, J.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2010-07-01

    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 {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 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

  17. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

    PubMed

    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

    2010-07-09

    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 (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 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

  18. Effects of isomers of apomorphines on dopamine receptors in striatal and limbic tissue of rat brain

    SciTech Connect

    Kula, N.S.; Baldessarini, R.J.; Bromley, S.; Neumeyer, J.L.

    1985-09-16

    The optical isomers of apomorphine (APO) and N-propylnorapomorphine (NPA) were interacted with three biochemical indices of dopamine (Da) receptors in extrapyramidal and limbic preparations of rat brain tissues. There were consistent isomeric preferences for the R(-) configuration of both DA analogs in stimulation adenylate cyclase (D-1 sites) and in competing for high affinity binding of /sup 3/H-spiroperidol (D-2 sites) and of /sup 3/H-ADTN (DA agonist binding sites) in striatal tissue, with lesser isomeric differences in the limbic tissue. The S(+) apomorphines did not inhibit stimulation of adenylate cyclase by DA. The tendency for greater activity of higher apparent affinity of R(-) apomorphines in striatum may reflect the evidently greater abundance of receptor sites in that region. There were only small regional differences in interactions of the apomorphine isomers with all three receptor sites, except for a strong preference of (-)NPA for striatal D-2 sites. These results do not parallel our recent observations indicating potent and selective antidopaminergic actions of S(+) apomorphines in the rat limbic system. They suggest caution in assuming close parallels between current biochemical functional, especially behavioral, methods of evaluating dopamine receptors of mammalian brain.

  19. Restoring Conscious Arousal During Focal Limbic Seizures with Deep Brain Stimulation.

    PubMed

    Kundishora, Adam J; Gummadavelli, Abhijeet; Ma, Chanthia; Liu, Mengran; McCafferty, Cian; Schiff, Nicholas D; Willie, Jon T; Gross, Robert E; Gerrard, Jason; Blumenfeld, Hal

    2016-03-03

    Impaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one-sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals. Here, we investigate deep brain stimulation to improve level of conscious arousal in a rat model of focal limbic seizures. We found that dual-site stimulation of the central lateral nucleus of the intralaminar thalamus (CL) and the pontine nucleus oralis (PnO) bilaterally during focal limbic seizures restored normal-appearing cortical electrophysiology and markedly improved behavioral arousal. In contrast, single-site bilateral stimulation of CL or PnO alone was insufficient to achieve the same result. These findings support the "network inhibition hypothesis" that focal limbic seizures impair consciousness through widespread inhibition of subcortical arousal. Driving subcortical arousal function would be a novel therapeutic approach to some forms of refractory epilepsy and may be compatible with devices already in use for responsive neurostimulation. Multisite deep brain stimulation of subcortical arousal structures may benefit not only patients with epilepsy but also those with other disorders of consciousness.

  20. Exposure to HIV-1 Tat in brain impairs sensorimotor gating and activates microglia in limbic and extralimbic brain regions of male mice.

    PubMed

    Paris, Jason J; Singh, Harminder D; Carey, Amanda N; McLaughlin, Jay P

    2015-09-15

    Human immunodeficiency virus (HIV) infection is associated with mood disorders and behavioral disinhibition. Impairments in sensorimotor gating and associated neurocognitive disorders are reported, but the HIV-proteins and mechanisms involved are not known. The regulatory HIV-1 protein, Tat, is neurotoxic and its expression in animal models increases anxiety-like behavior concurrent with neuroinflammation and structural changes in limbic and extra-limbic brain regions. We hypothesized that conditional expression of HIV-1 Tat1-86 in the GT-tg bigenic mouse model would impair sensorimotor gating and increase microglial reactivity in limbic and extralimbic brain regions. Conditional Tat induction via doxycycline (Dox) treatment (0-125 mg/kg, i.p., for 1-14 days) significantly potentiated the acoustic startle reflex (ASR) of GT-tg mice and impaired prepulse inhibition (PPI) of this response in a dose-dependent manner when Dox (100mg/kg) was administered for brief (1 day) or prolonged (daily for 7 days) intervals. A greater proportion of active/reactive Iba1-labeled microglia was seen in the anterior cingulate cortex (ACC), dentate gyrus, and nucleus accumbens core when Tat protein was induced under either brief or prolonged expression conditions. Other subregions of the medial prefrontal cortex, amygdala, hippocampal formation, ventral tegmental area, and ventral pallidum also displayed Tat-induced microglial activation, but only the activation observed in the ACC recapitulated the pattern of ASR and PPI behaviors. Tat exposure also increased frontal cortex GFAP. Pretreatment with indomethacin attenuated the behavioral effects of brief (but not prolonged) Tat-exposure. Overall, exposure to HIV-1 Tat protein induced sensorimotor deficits associated with acute and persistent neuroinflammation in limbic/extralimbic brain regions. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Exposure to HIV-1 Tat in brain impairs sensorimotor gating and activates microglia in limbic and extralimbic brain regions of male mice

    PubMed Central

    Paris, Jason J.; Singh, Harminder D.; Carey, Amanda N.; McLaughlin, Jay P.

    2015-01-01

    Human immunodeficiency virus (HIV) infection is associated with mood disorders and behavioral disinhibition. Impairments in sensorimotor gating and associated neurocognitive disorders are reported, but the HIV-proteins and mechanisms involved are not known. The regulatory HIV-1 protein, Tat, is neurotoxic and its expression in animal models increases anxiety-like behavior concurrent with neuroinflammation and structural changes in limbic and extra-limbic brain regions. We hypothesized that conditional expression of HIV-1 Tat1–86 in the GT-tg bigenic mouse model would impair sensorimotor gating and increase microglial reactivity in limbic and extralimbic brain regions. Conditional Tat induction via doxycycline (Dox) treatment (0–125 mg/kg, i.p., for 1–14 days) significantly potentiated the acoustic startle reflex (ASR) of GT-tg mice and impaired prepulse inhibition (PPI) of this response in a dose-dependent manner when Dox (100 mg/kg) was administered for brief (1 day) or prolonged (daily for 7 days) intervals. A greater proportion of active/reactive Iba1-labeled microglia was seen in the anterior cingulate cortex (ACC), dentate gyrus, and nucleus accumbens core when Tat protein was induced under either brief or prolonged expression conditions. Other subregions of the medial prefrontal cortex, amygdala, hippocampal formation, ventral tegmental area, and ventral pallidum also displayed Tat-induced microglial activation, but only the activation observed in the ACC recapitulated the pattern of ASR and PPI behaviors. Tat exposure also increased frontal cortex GFAP. Pretreatment with indomethacin attenuated the behavioral effects of brief (but not prolonged) Tat-exposure. Overall, exposure to HIV-1 Tat protein induced sensorimotor deficits associated with acute and persistent neuroinflammation in limbic/extralimbic brain regions. PMID:26005128

  2. Acute injection of drugs with low addictive potential (delta(9)-tetrahydrocannabinol, 3,4-methylenedioxymethamphetamine, lysergic acid diamide) causes a much higher c-fos expression in limbic brain areas than highly addicting drugs (cocaine and morphine).

    PubMed

    Erdtmann-Vourliotis, M; Mayer, P; Riechert, U; Höllt, V

    1999-08-25

    It is regarded as a common pharmacological property responsible for the addictive potential of drugs of abuse that they are able to activate brain areas involved in the sensation of pleasure, especially the nucleus accumbens. To investigate the connection between addictive potential and stimulation of critical brain areas in more detail, we studied c-fos accumulation in response to various addicting drugs in direct comparison. The substances were injected into drug-naive rats, and c-fos mRNA levels were measured throughout the brain by in situ hybridization. Cocaine in a high dose of 50 mg/kg yielded only a discrete c-fos expression in the medial and central striatum. Morphine (50 mg/kg) caused a weak c-fos synthesis in the lateral septum. THC (delta(9)-tetrahydrocannabinol), 25 mg/kg, induced c-fos mRNA again in the lateral septum and furthermore in large parts of the striatum including the nucleus accumbens. LSD (lysergic acid diamide), 1 mg/kg, elicited a similar c-fos expression pattern as THC, but there was additionally a very strong hybridization signal in the cerebral cortex, especially in the upper layers, and in the ventral part of the periaqueductal gray. The widest range of brain areas was activated by MDMA (3, 4-methylenedioxymethamphetamine, 'ecstasy'), 6 mg/kg. In addition to the regions that responded to LSD, there was a very pronounced c-fos signal in the nucleus accumbens core and shell and in the mammillary nuclei. Taken together, our study revealed that the drugs with the highest addictive potential, cocaine and morphine, yielded a very low c-fos synthesis throughout the brain whereas the brain regions closely linked to pleasure (especially the nucleus accumbens) responded strongly to drugs with an apparently lower addictive potential (THC, LSD, MDMA).

  3. Mapping the connectivity of serotonin transporter immunoreactive axons to excitatory and inhibitory neurochemical synapses in the mouse limbic brain.

    PubMed

    Belmer, Arnauld; Klenowski, Paul M; Patkar, Omkar L; Bartlett, Selena E

    2017-04-01

    Serotonin neurons arise from the brainstem raphe nuclei and send their projections throughout the brain to release 5-HT which acts as a modulator of several neuronal populations. Previous electron microscopy studies in rats have morphologically determined the distribution of 5-HT release sites (boutons) in certain brain regions and have shown that 5-HT containing boutons form synaptic contacts that are either symmetric or asymmetric. In addition, 5-HT boutons can form synaptic triads with the pre- and postsynaptic specializations of either symmetrical or asymmetrical synapses. However, due to the labor intensive processing of serial sections required by electron microscopy, little is known about the neurochemical properties or the quantitative distribution of 5-HT triads within whole brain or discrete subregions. Therefore, we used a semi-automated approach that combines immunohistochemistry and high-resolution confocal microscopy to label serotonin transporter (SERT) immunoreactive axons and reconstruct in 3D their distribution within limbic brain regions. We also used antibodies against key pre- (synaptophysin) and postsynaptic components of excitatory (PSD95) or inhibitory (gephyrin) synapses to (1) identify putative 5-HTergic boutons within SERT immunoreactive axons and, (2) quantify their close apposition to neurochemical excitatory or inhibitory synapses. We provide a 5-HTergic axon density map and have determined the ratio of synaptic triads consisting of a 5-HT bouton in close proximity to either neurochemical excitatory or inhibitory synapses within different limbic brain areas. The ability to model and map changes in 5-HTergic axonal density and the formation of triadic connectivity within whole brain regions using this rapid and quantitative approach offers new possibilities for studying neuroplastic changes in the 5-HTergic pathway.

  4. Limbic brain activation for maternal acoustic perception and responding is different in mothers and virgin female mice.

    PubMed

    Geissler, Diana B; Sabine Schmidt, H; Ehret, Günter

    2013-01-01

    Mothers are primed to become maternal through hormonal changes during pregnancy and delivery of young, virgin females need experience with young for performing maternally. The activation of brain areas controlling maternal behavior can be studied by stimulus-induced expression of the immediate-early gene Fos and immunocytochemical labeling of the FOS protein in activated cells. With this technique we identified areas of the mouse limbic system stimulated by acoustically adequate or inadequate models of pup ultrasounds that, if perceived as adequate, direct the search for lost pups (phonotaxis). Behavioral observations and neural activation data suggest that adequate (50 kHz long tones) and inadequate ultrasound models (50 kHz short or 20 kHz long tones) are differently processed in limbic areas of mothers and virgin females with 1 or 5 days of pup-caring experience depending on the news value and the recognition of the stimuli: High numbers of FOS-positive cells in the medial preoptic area, lateral septum, and bed nucleus of the stria terminalis (mothers and virgins) relate to the salience (news value) of the perceived sounds; contextual stress may be reflected by high activation in parts of the amygdala and the ventromedial hypothalamus (virgins); high activation in the piriform cortex suggests associative learning of adequate sounds and in the entorhinal cortex remembering associations of adequate sounds with pups (virgins). Thus brain areas were differently activated in animals with maternal emotions, however different responses to pup cues depending on how they got primed to behave maternally and on how they evaluated the stimulation context. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Acupuncture, the Limbic System, and the Anticorrelated Networks of the Brain

    PubMed Central

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

    2013-01-01

    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

  6. 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

  7. Limbic areas are functionally decoupled and visual cortex takes a more central role during fear conditioning in humans

    PubMed Central

    Lithari, Chrysa; Moratti, Stephan; Weisz, Nathan

    2016-01-01

    Going beyond the focus on isolated brain regions (e.g. amygdala), recent neuroimaging studies on fear conditioning point to the relevance of a network of mutually interacting brain regions. In the present MEG study we used Graph Theory to uncover changes in the architecture of the brain functional network shaped by fear conditioning. Firstly, induced power analysis revealed differences in local cortical excitability (lower alpha and beta power) between CS+ and CS− localized to somatosensory cortex and insula. What is more striking however is that the graph theoretical measures unveiled a re-organization of brain functional connections, not evident using conventional power analysis. Subcortical fear-related structures exhibited reduced connectivity with temporal and frontal areas rendering the overall brain functional network more sparse during fear conditioning. At the same time, the calcarine took on a more central role in the network. Interestingly, the more the connectivity of limbic areas is reduced, the more central the role of the occipital cortex becomes. We speculated that both, the reduced coupling in some regions and the emerging centrality of others, contribute to the efficient processing of fear-relevant information during fear learning. PMID:27381479

  8. Limbic areas are functionally decoupled and visual cortex takes a more central role during fear conditioning in humans.

    PubMed

    Lithari, Chrysa; Moratti, Stephan; Weisz, Nathan

    2016-07-06

    Going beyond the focus on isolated brain regions (e.g. amygdala), recent neuroimaging studies on fear conditioning point to the relevance of a network of mutually interacting brain regions. In the present MEG study we used Graph Theory to uncover changes in the architecture of the brain functional network shaped by fear conditioning. Firstly, induced power analysis revealed differences in local cortical excitability (lower alpha and beta power) between CS+ and CS- localized to somatosensory cortex and insula. What is more striking however is that the graph theoretical measures unveiled a re-organization of brain functional connections, not evident using conventional power analysis. Subcortical fear-related structures exhibited reduced connectivity with temporal and frontal areas rendering the overall brain functional network more sparse during fear conditioning. At the same time, the calcarine took on a more central role in the network. Interestingly, the more the connectivity of limbic areas is reduced, the more central the role of the occipital cortex becomes. We speculated that both, the reduced coupling in some regions and the emerging centrality of others, contribute to the efficient processing of fear-relevant information during fear learning.

  9. Effects of lithium and aripiprazole on brain stimulation reward and neuroplasticity markers in the limbic forebrain.

    PubMed

    Mavrikaki, Maria; Schintu, Nicoletta; Kastellakis, Andreas; Nomikos, George G; Svenningsson, Per; Panagis, George

    2014-04-01

    Bipolar disorder (BD) is a severe pathological condition with impaired reward-related processing. The present study was designed to assess the effects of two commonly used BD medications, the mood stabilizer lithium chloride (LiCl) and the atypical antipsychotic and antimanic agent aripiprazole, in an animal model of reward and motivation and on markers of neuroplasticity in the limbic forebrain in rats. We utilized intracranial self-simulation (ICSS) to assess the effects of acute and chronic administration of LiCl and aripiprazole on brain stimulation reward, and phosphorylation studies to determine their effects on specific cellular neuroplasticity markers, i.e., the phosphorylation of CREB and crucial phosphorylation sites on the GluA1 subunit of AMPA receptors and the NA1 and NA2B subunits of NMDA receptors, in the limbic forebrain. Chronic LiCl induced tolerance to the anhedonic effect of the drug observed after acute administration, while chronic aripiprazole induced a sustained anhedonic effect. These distinct behavioral responses might be related to differences in molecular markers of neuroplasticity. Accordingly, we demonstrated that chronic LiCl, but not aripiprazole, decreased phosphorylation of CREB at the Ser133 site and NA1 at the Ser896 site in the prefrontal cortex and GluA1 at the Ser831 site and NA2B at the Ser1303 site in the ventral striatum. The present study provides evidence for BD medication-evoked changes in reward and motivation processes and in specific markers of neuronal plasticity in the limbic forebrain, promoting the notion that these drugs may blunt dysregulated reward processes in BD by counteracting neuronal plasticity deficits.

  10. [Disorders of neurogenesis of cortical and subcortical structures in rat brain limbic system during fetal alcohol syndrome formation].

    PubMed

    Svanidze, I K; Museridze, D P; Didimova, E V; Sanikidze, T V; Gegenava, L G; Gvinadze, N N

    2012-01-01

    Disorders of neurogenesis of cortical and subcortical structures in rat brain limbic system were studied in the offspring of rats that received ethanol during pregnancy. The methods used included the staining of histological sections with cresyl violet, in vitro culture, and electron paramagnetic resonance. Prenatal alcohol intoxication was shown to induce the disturbances in proliferative activity of granular layer cells in the hippocampal dentate gyrus, neuron- and glioblast migration, enhancement of free NO and lipoperoxide production and cell death. This resulted in the changes in the number of neurons in cortical and subcortical structures of rat brain limbic system and in fetal alcohol syndrome formation.

  11. 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.

  12. Peripherally Administered Non-peptide Oxytocin Antagonist, L368,899®, Accumulates in Limbic Brain Areas: A New Pharmacological Tool for the Study of Social Motivation in Non-Human Primates

    PubMed Central

    Boccia, Maria L.; Goursaud, Anne-Pierre S.; Bachevalier, Jocelyne; Anderson, Kenneth D.; Pedersen, Cort A.

    2009-01-01

    Central administration of oxytocin (OT) antagonists inhibits maternal and sexual behavior in non-primates, providing the strongest experimental evidence that endogenous OT facilitates these behaviors. While there have been a few reports that ICV administration of OT increases social behaviors in monkeys, no studies to date have assessed the effects of OT antagonists. Therefore, we studied in rhesus monkeys whether L368,899®, a non-peptide antagonist produced by Merck that selectively blocks the human uterine OT receptor, penetrates the CNS after peripheral administration and alters female maternal and sexual behavior. In two studies in four male monkeys, L368,899 was injected iv (1 mg/kg) after which (1) CSF samples were collected at intervals over 4 h and (2) brains were collected at 60 min. Assay of samples confirmed that iv-administered L368,899 entered CSF and accumulated in the hypothalamus, septum, orbitofrontal cortex, amygdala and hippocampus, but not other areas. An adult female monkey was tested for interest in either an infant or sexual behavior, receiving a different iv treatment prior to each test (1 or 3 mg/kg of L368,899 or saline) OT antagonist treatment reduced or eliminated interest in the infant and sexual behavior. These results, although preliminary, are the first to directly implicate endogenous OT in activation of primate maternal interest and sexual behavior. While it remains to be empirically demonstrated that peripherally administered L368,899 blocks central OT receptors, our behavioral findings suggest that this non-peptide antagonist may facilitate testing OT involvement in a variety of social and other behaviors in primates. PMID:17583705

  13. Loss of Microstructural Integrity in the Limbic-Subcortical Networks for Acute Symptomatic Traumatic Brain Injury

    PubMed Central

    Zhu, Yanan; Li, Zhengjun; Bai, Lijun; Tao, Yin; Sun, Chuanzhu; Li, Min; Zheng, Longmei; Zhu, Bao; Yao, Jun; Zhou, Heping; Zhang, Ming

    2014-01-01

    Previous studies reported discrepant white matter diffusivity in mild traumatic brain injury (mTBI) on the base of Glasgow Coma Scale, which are unreliable for some TBI severity indicators and the frequency of missing documentation in the medical record. In the present study, we adopted the Mayo classification system for TBI severity. In this system, the mTBI is also divided into two groups as “probable and symptomatic” TBI. We aimed to investigate altered microstructural integrity in symptomatic acute TBI (<1 week) by using tract-based spatial statics (TBSS) approach. A total of 12 patients and 13 healthy volunteers were involved and underwent MRI scans including conventional scan, and SWI and DTI. All the patients had no visible lesions by using conventional and SWI neuroimaging techniques, while showing widespread declines in the fractional anisotropy (FA) of gray matter and white matter throughout the TBSS skeleton, particularly in the limbic-subcortical structures. By contrast, symptomatic TBI patients showed no significant enhanced changes in FA compared to the healthy controls. A better understanding of the acute changes occurring following symptomatic TBI may increase our understanding of neuroplasticity and continuing degenerative change, which, in turn, may facilitate advances in management and intervention. PMID:24695757

  14. 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

    2017-02-28

    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.

  15. Mild Traumatic Brain Injury with Social Defeat Stress Alters Anxiety, Contextual Fear Extinction, and Limbic Monoamines in Adult Rats

    PubMed Central

    Davies, Daniel R.; Olson, Dawne; Meyer, Danielle L.; Scholl, Jamie L.; Watt, Michael J.; Manzerra, Pasquale; Renner, Kenneth J.; Forster, Gina L.

    2016-01-01

    Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes. PMID:27147992

  16. fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity.

    PubMed

    Paret, Christian; Ruf, Matthias; Gerchen, Martin Fungisai; Kluetsch, Rosemarie; Demirakca, Traute; Jungkunz, Martin; Bertsch, Katja; Schmahl, Christian; Ende, Gabriele

    2016-01-15

    Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: p<.05 at cluster-level). Task-dependent increases in amygdala-vmPFC connectivity were predicted by picture arousal (β=.59, p<.05). A dynamic causal modeling analysis with Bayesian model selection aimed at further characterizing the underlying causal structure and favored a bottom-up model assuming predominant information flow from the amygdala to the vmPFC (xp=.90). The results were complemented by the observation of task-dependent alterations in functional connectivity of the vmPFC with the visual cortex and the ventrolateral PFC in the experimental group (Condition t-contrast: p<.05 at cluster-level). Taken together, the results underscore the potential of amygdala fMRI neurofeedback to influence functional connectivity in key networks of emotion processing and regulation. This may be beneficial for patients suffering from severe emotion dysregulation by improving neural self-regulation.

  17. Differential developmental trajectories for CB1 cannabinoid receptor expression in limbic/associative and sensorimotor cortical areas

    PubMed Central

    Heng, Lijun; Beverley, Joel A.; Steiner, Heinz; Tseng, Kuei Y.

    2010-01-01

    Cannabis use during adolescence is associated with an increased risk for schizophrenia and other disorders. The neuronal basis is unclear, but prefrontal cortical mechanisms have been implicated. Here, we investigated developmental changes in the endocannabinoid system by assessing expression and function of the CB1 cannabinoid receptor in prefrontal and other cortical areas in juvenile (postnatal day 25, P25), adolescent (P40) and adult (P70) rats. Overall, the expression of CB1 receptors in the cortex is highest in juveniles and drops thereafter towards adult levels. However, CB1 receptor expression follows distinct developmental trajectories in different cortical areas. The most pronounced and progressive decrease in CB1 expression was observed in medial prefrontal and other limbic/associative regions. In contrast, major changes in sensorimotor cortices occurred only after P40. We also assessed electrophysiological measures of CB1 receptor function and found that CB1-dependent inhibition of synaptic transmission in the prefrontal cortex follows the same developmental trajectory as observed for receptor expression. Together, these findings indicate that CB1 receptor-mediated signaling decreases during development, but is differentially regulated in limbic/associative vs. sensorimotor systems. Therefore, cannabis use during adolescence likely differentially affects limbic/associative and sensorimotor cortical circuits. PMID:20687106

  18. Limbic brain responses in mothers with post-traumatic stress disorder and comorbid dissociation to video clips of their children.

    PubMed

    Moser, Dominik Andreas; Aue, Tatjana; Wang, Zhishun; Rusconi Serpa, Sandra; Favez, Nicolas; Peterson, Bradley Scott; Schechter, Daniel Scott

    2013-09-01

    Maternal dissociative symptoms which can be comorbid with interpersonal violence-related post-traumatic stress disorder (IPV-PTSD) have been linked to decreased sensitivity and responsiveness to children's emotional communication. This study examined the influence of dissociation on neural activation independently of IPV-PTSD symptom severity when mothers watch video-stimuli of their children during stressful and non-stressful mother-child interactions. Based on previous observations in related fields, we hypothesized that more severe comorbid dissociation in IPV-PTSD would be associated with lower limbic system activation and greater neural activity in regions of the emotion regulation circuit such as the medial prefrontal cortex and dorsolateral prefrontal cortex (dlPFC). Twenty mothers (of children aged 12-42 months), with and without IPV-PTSD watched epochs showing their child during separation and play while undergoing functional magnetic resonance imaging (fMRI). Multiple regression indicated that when mothers diagnosed with IPV-PTSD watched their children during separation compared to play, dissociative symptom severity was indeed linked to lowered activation within the limbic system, while greater IPV-PTSD symptom severity was associated with heightened limbic activity. Concerning emotion regulation areas, there was activation associated to dissociation in the right dlPFC. Our results are likely a neural correlate of affected mothers' reduced capacity for sensitive responsiveness to their young child following exposure to interpersonal stress, situations that are common in day-to-day parenting.

  19. 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.

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

    PubMed

    Widge, Alik S; Moritz, Chet T

    2014-04-01

    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). 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. 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. 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.

  1. Serotonergic modulation of the limbic system.

    PubMed

    Hensler, Julie G

    2006-01-01

    The limbic system is composed of cortical as well as subcortical structures, which are intimately interconnected. The resulting macrostructure is responsible for the generation and expression of motivational and affective states. Especially high levels of serotonin are found in limbic forebrain structures. Serotonin projections to these structures, which arise from serotonergic cell body groups in the midbrain, form a dense plexus of axonal processes. In many areas of the limbic system, serotonergic neurotransmission can best be described as paracrine or volume transmission, and thus serotonin is believed to play a neuromodulatory role in the brain. Serotonergic projections to limbic structures, arising primarily from the dorsal and median raphe nuclei, compose two distinct serotonergic systems differing in their topographic organization, electrophysiological characteristics, morphology, as well as sensitivity to neurotoxins and perhaps psychoactive or therapeutic agents. These differences may be extremely important in understanding the role of these two serotonergic systems in normal brain function and in mental illness. Central serotonergic neurons or receptors are targets for a variety of therapeutic agents used in the treatment of disorders of the limbic system.

  2. 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

  3. Ethanol-induced alterations of c-Fos immunoreactivity in specific limbic brain regions following ethanol discrimination training.

    PubMed

    Besheer, Joyce; Schroeder, Jason P; Stevenson, Rebekah A; Hodge, Clyde W

    2008-09-26

    The discriminative stimulus properties of ethanol are functionally regulated by ionotropic GABA(A) and NMDA receptors in specific limbic brain regions including the nucleus accumbens, amygdala, and hippocampus, as determined by microinjection studies. The purpose of the present work was to further investigate potential neural substrates of ethanol's discriminative stimulus effects by examining if ethanol discrimination learning produces changes in brain regional response to ethanol. To accomplish this goal, immunohistochemistry was used to assess the effects of ethanol (2 g/kg) on c-Fos immunoreactivity (Fos-IR). Comparisons in ethanol-induced Fos-IR were made between a group of rats that was trained to discriminate the stimulus properties of ethanol (2 g/kg, IG) from water (IG) and a drug/behavior-matched control group that did not receive differential reinforcement for lever selection, which precluded acquisition of discriminative stimulus control by ethanol. In some brain regions discrimination training had no effect on ethanol-induced Fos-IR changes (caudate putamen, bed nucleus of the stria terminalis, and CA1 region of the hippocampus). In contrast, discrimination training altered the pattern of ethanol-induced Fos-IR in the nucleus accumbens (core), medial septum, and the hippocampus (dentate and CA3). These results indicate that having behavior under the stimulus control of ethanol can change ethanol-induced Fos-IR in some brain regions. This suggests that learning about the subjective properties of ethanol produces adaptive changes in how the brain responds to acute ethanol exposure.

  4. 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

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

    PubMed

    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 21(st) century will continue in this three-part essay-editorial, exclusively researched and written for the readers of Surgical Neurology International.

  6. Increased Functional Activation of Limbic Brain Regions during Negative Emotional Processing in Migraine

    PubMed Central

    Wilcox, Sophie L.; Veggeberg, Rosanna; Lemme, Jordan; Hodkinson, Duncan J.; Scrivani, Steven; Burstein, Rami; Becerra, Lino; Borsook, David

    2016-01-01

    Pain is both an unpleasant sensory and emotional experience. This is highly relevant in migraine where cortical hyperexcitability in response to sensory stimuli (including pain, light, and sound) has been extensively reported. However, migraine may feature a more general enhanced response to aversive stimuli rather than being sensory-specific. To this end we used functional magnetic resonance imaging to assess neural activation in migraineurs interictaly in response to emotional visual stimuli from the International Affective Picture System. Migraineurs, compared to healthy controls, demonstrated increased neural activity in response to negative emotional stimuli. Most notably in regions overlapping in their involvement in both nociceptive and emotional processing including the posterior cingulate, caudate, amygdala, and thalamus (cluster corrected, p < 0.01). In contrast, migraineurs and healthy controls displayed no and minimal differences in response to positive and neutral emotional stimuli, respectively. These findings support the notion that migraine may feature more generalized altered cerebral processing of aversive/negative stimuli, rather than exclusively to sensory stimuli. A generalized hypersensitivity to aversive stimuli may be an inherent feature of migraine, or a consequential alteration developed over the duration of the disease. This proposed cortical-limbic hypersensitivity may form an important part of the migraine pathophysiology, including psychological comorbidity, and may represent an innate sensitivity to aversive stimuli that underpins attack triggers, attack persistence and (potentially) gradual headache chronification. PMID:27507939

  7. Imaging signatures of altered brain responses in small-fiber neuropathy: reduced functional connectivity of the limbic system after peripheral nerve degeneration.

    PubMed

    Hsieh, Paul-Chen; Tseng, Ming-Tsung; Chao, Chi-Chao; Lin, Yea-Huey; Tseng, Wen-Yih I; Liu, Kuan-Hong; Chiang, Ming-Chang; Hsieh, Sung-Tsang

    2015-05-01

    Small-fiber neuropathy (SFN) is hallmarked by degeneration of small unmyelinated peripheral nerve fibers in the skin. Traditionally, it has been considered as a pure disorder of the peripheral nervous system. Nevertheless, previous work found that dysfunction of skin nerves led to abnormal recruitment of pain-related regions, suggesting that the brain may be affected in SFN. This report combined structural and functional magnetic resonance imaging to identify structural and functional changes in the brain of 19 patients with SFN compared with 17 healthy controls. We applied tensor-based morphometry to detect brain structural alterations in SFN. Greater volume reduction in pain-processing regions, particularly the bilateral anterior cingulate cortices (ACCs), was associated with greater depletion of intraepidermal nerve fibers, a pathological biomarker of skin nerve degeneration. Based on the hypothesis that structural alterations in the pain-processing regions might impair their functional connectivity, we further applied psychophysiological interaction analysis to assess functional connectivity of the ACCs during noxious heat stimulation. There was significant reduction in functional connectivity from the ACCs to the limbic areas (the parahippocampal gyrus and the posterior cingulate cortex), pain-processing area (the insula), and visuospatial areas (the cuneus). Moreover, the degree of reduction in functional connectivity for the ACC to the amygdala and the precuneus was linearly correlated with the severity of intraepidermal nerve fiber depletion. Our findings suggest that SFN is not a pure peripheral nervous system disorder. The pain-related brain networks tend to break into functionally independent components, with severity linked to the degree of skin nerve degeneration.

  8. Divergent projections of catecholaminergic neurons in the nucleus of the solitary tract to limbic forebrain and medullary autonomic brain regions.

    PubMed

    Reyes, Beverly A S; Van Bockstaele, Elisabeth J

    2006-10-30

    The nucleus of the solitary tract (NTS) is a critical structure involved in coordinating autonomic and visceral activities. Previous independent studies have demonstrated efferent projections from the NTS to the nucleus paragigantocellularis (PGi) and the central nucleus of the amygdala (CNA) in rat brain. To further characterize the neural circuitry originating from the NTS with postsynaptic targets in the amygdala and medullary autonomic targets, distinct green or red fluorescent latex microspheres were injected into the PGi and the CNA, respectively, of the same rat. Thirty-micron thick tissue sections through the lower brainstem and forebrain were collected. Every fourth section through the NTS region was processed for immunocytochemical detection of tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Retrogradely labeled neurons from the PGi or CNA were distributed throughout the rostro-caudal segments of the NTS. However, the majority of neurons containing both retrograde tracers were distributed within the caudal third of the NTS. Cell counts revealed that approximately 27% of neurons projecting to the CNA in the NTS sent collateralized projections to the PGi while approximately 16% of neurons projecting to the PGi sent collateralized projections to the CNA. Interestingly, more than half of the PGi and CNA-projecting neurons in the NTS expressed TH immunoreactivity. These data indicate that catecholaminergic neurons in the NTS are poised to simultaneously coordinate activities in limbic and medullary autonomic brain regions.

  9. Lorazepam dose-dependently decreases risk-taking related activation in limbic areas.

    PubMed

    Arce, Estibaliz; Miller, Daniel A; Feinstein, Justin S; Stein, Murray B; Paulus, Martin P

    2006-11-01

    Several studies have examined the role of different neurotransmitter systems in modulating risk-taking behavior. This investigation was aimed to determine whether the benzodiazepine lorazepam dose-dependently alters risk-taking behavior and underlying neural substrates. Fifteen healthy, nonsmoking, individuals (six women, nine men), aged 18-39 years (mean 27.6 +/- 1.4 years) with 12-18 years of education (mean 15.6 +/- 0.3 years) underwent functional magnetic resonance imaging while performing a risk-taking decision-making task. Our results show that lorazepam did not affect risky behavior at 0.25 and 1 mg, but dose-dependently attenuated activation in (a) the amygdala and medial prefrontal cortex during the response selection phase, and in (b) the bilateral insular cortex and amygdala during the outcome (i.e., rewarded or punished) phase. Furthermore, a lorazepam-induced increase in insular cortex activation was associated with less risky responses. Taken together, our findings support the idea that GABAergic modulation in limbic and paralimbic structures is important during both the response selection and outcome phase of risk-taking decision-making.

  10. Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder.

    PubMed

    Monkul, E S; Hatch, J P; Nicoletti, M A; Spence, S; Brambilla, P; Lacerda, A L T; Sassi, R B; Mallinger, A G; Keshavan, M S; Soares, J C

    2007-04-01

    Our knowledge about the neurobiology of suicide is limited. It has been proposed that suicidal behavior generally requires biological abnormalities concomitant with the personality trait of impulsivity/aggression, besides an acute psychiatric illness or psychosocial stressor. We investigated fronto-limbic anatomical brain abnormalities in suicidal and non-suicidal adult female patients with unipolar depression. Our sample consisted of seven suicidal unipolar patients, 10 non-suicidal unipolar patients and 17 healthy female comparison subjects. The criterion for suicidality was one or more documented lifetime suicide attempts. A 1.5T GE Signa Imaging System running version Signa 5.4.3 software was used to acquire the magnetic resonance imaging images. All anatomical structures were measured blindly, with the subjects' identities and group assignments masked. We used analysis of covariance with age and intracranial volume as covariates and the Tukey-Kramer procedure to compare suicidal patients, non-suicidal patients and healthy comparison subjects. Suicidal patients had smaller right and left orbitofrontal cortex gray matter volumes compared with healthy comparison subjects. Suicidal patients had larger right amygdala volumes than non-suicidal patients. Abnormalities in the orbitofrontal cortex and amygdala in suicidal patients may impair decision-making and predispose these patients to act more impulsively and to attempt suicide.

  11. Systemic injection of kainic acid: Gliosis in olfactory and limbic brain regions quantified with ( sup 3 H)PK 11195 binding autoradiography

    SciTech Connect

    Altar, C.A.; Baudry, M. )

    1990-09-01

    Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of (3H)PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in (3H)PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in (3H)PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of (3H)PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in (3H)PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of (3H)PK 11195 is a valuable tool to quantify the extent of neuronal degeneration.

  12. Area Prostriata in the Human Brain.

    PubMed

    Mikellidou, Kyriaki; Kurzawski, Jan W; Frijia, Francesca; Montanaro, Domenico; Greco, Vincenzo; Burr, David C; Morrone, Maria Concetta

    2017-10-09

    Area prostriata is a cortical area at the fundus of the calcarine sulcus, described anatomically in humans [1-5] and other primates [6-9]. It is lightly myelinated and lacks the clearly defined six-layer structure evident throughout the cerebral cortex, with a thinner layer 4 and thicker layer 2 [10], characteristic of limbic cortex [11]. In the marmoset and rhesus monkey, area prostriata has cortical connections with MT+ [12], the cingulate motor cortex [8], the auditory cortex [13], the orbitofrontal cortex, and the frontal polar cortices [14]. Here we use functional magnetic resonance together with a wide-field projection system to study its functional properties in humans. With population receptive field mapping [15], we show that area prostriata has a complete representation of the visual field, clearly distinct from the adjacent area V1. As in the marmoset, the caudal-dorsal border of human prostriata-abutting V1-represents the far peripheral visual field, with eccentricities decreasing toward its rostral boundary. Area prostriata responds strongly to very fast motion, greater than 500°/s. The functional properties of area prostriata suggest that it may serve to alert the brain quickly to fast visual events, particularly in the peripheral visual field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Fronto-Limbic Brain Dysfunction during the Regulation of Emotion in Schizophrenia

    PubMed Central

    Eack, Shaun M.; Wojtalik, Jessica A.; Barb, Scott M.; Newhill, Christina E.; Keshavan, Matcheri S.; Phillips, Mary L.

    2016-01-01

    Schizophrenia is characterized by significant and widespread impairments in the regulation of emotion. Evidence is only recently emerging regarding the neural basis of these emotion regulation impairments, and few studies have focused on the regulation of emotion during effortful cognitive processing. To examine the neural correlates of deficits in effortful emotion regulation, schizophrenia outpatients (N = 20) and age- and gender-matched healthy volunteers (N = 20) completed an emotional faces n-back task to assess the voluntary attentional control subprocess of emotion regulation during functional magnetic resonance imaging. Behavioral measures of emotional intelligence and emotion perception were administered to examine brain-behavior relationships with emotion processing outcomes. Results indicated that patients with schizophrenia demonstrated significantly greater activation in the bilateral striatum, ventromedial prefrontal, and right orbitofrontal cortices during the effortful regulation of positive emotional stimuli, and reduced activity in these same regions when regulating negative emotional information. The opposite pattern of results was observed in healthy individuals. Greater fronto-striatal response to positive emotional distractors was significantly associated with deficits in facial emotion recognition. These findings indicate that abnormalities in striatal and prefrontal cortical systems may be related to deficits in the effortful emotion regulatory process of attentional control in schizophrenia, and may significantly contribute to emotion processing deficits in the disorder. PMID:26930284

  14. Musical Creativity “Revealed” in Brain Structure: Interplay between Motor, Default Mode, and Limbic Networks

    PubMed Central

    Bashwiner, David M.; Wertz, Christopher J.; Flores, Ranee A.; Jung, Rex E.

    2016-01-01

    Creative behaviors are among the most complex that humans engage in, involving not only highly intricate, domain-specific knowledge and skill, but also domain-general processing styles and the affective drive to create. This study presents structural imaging data indicating that musically creative people (as indicated by self-report) have greater cortical surface area or volume in a) regions associated with domain-specific higher-cognitive motor activity and sound processing (dorsal premotor cortex, supplementary and pre-supplementary motor areas, and planum temporale), b) domain-general creative-ideation regions associated with the default mode network (dorsomedial prefrontal cortex, middle temporal gyrus, and temporal pole), and c) emotion-related regions (orbitofrontal cortex, temporal pole, and amygdala). These findings suggest that domain-specific musical expertise, default-mode cognitive processing style, and intensity of emotional experience might all coordinate to motivate and facilitate the drive to create music. PMID:26888383

  15. Musical Creativity "Revealed" in Brain Structure: Interplay between Motor, Default Mode, and Limbic Networks.

    PubMed

    Bashwiner, David M; Wertz, Christopher J; Flores, Ranee A; Jung, Rex E

    2016-02-18

    Creative behaviors are among the most complex that humans engage in, involving not only highly intricate, domain-specific knowledge and skill, but also domain-general processing styles and the affective drive to create. This study presents structural imaging data indicating that musically creative people (as indicated by self-report) have greater cortical surface area or volume in a) regions associated with domain-specific higher-cognitive motor activity and sound processing (dorsal premotor cortex, supplementary and pre-supplementary motor areas, and planum temporale), b) domain-general creative-ideation regions associated with the default mode network (dorsomedial prefrontal cortex, middle temporal gyrus, and temporal pole), and c) emotion-related regions (orbitofrontal cortex, temporal pole, and amygdala). These findings suggest that domain-specific musical expertise, default-mode cognitive processing style, and intensity of emotional experience might all coordinate to motivate and facilitate the drive to create music.

  16. Development of axonal pathways in the human fetal fronto-limbic brain: histochemical characterization and diffusion tensor imaging.

    PubMed

    Vasung, Lana; Huang, Hao; Jovanov-Milošević, Nataša; Pletikos, Mihovil; Mori, Susumu; Kostović, Ivica

    2010-10-01

    The development of cortical axonal pathways in the human brain begins during the transition between the embryonic and fetal period, happens in a series of sequential events, and leads to the establishment of major long trajectories by the neonatal period. We have correlated histochemical markers (acetylcholinesterase (AChE) histochemistry, antibody against synaptic protein SNAP-25 (SNAP-25-immunoreactivity) and neurofilament 200) with the diffusion tensor imaging (DTI) database in order to make a reconstruction of the origin, growth pattern and termination of the pathways in the period between 8 and 34 postconceptual weeks (PCW). Histological sections revealed that the initial outgrowth and formation of joined trajectories of subcortico-frontal pathways (external capsule, cerebral stalk-internal capsule) and limbic bundles (fornix, stria terminalis, amygdaloid radiation) occur by 10 PCW. As early as 11 PCW, major afferent fibers invade the corticostriatal junction. At 13-14 PCW, axonal pathways from the thalamus and basal forebrain approach the deep moiety of the cortical plate, causing the first lamination. The period between 15 and 18 PCW is dominated by elaboration of the periventricular crossroads, sagittal strata and spread of fibers in the subplate and marginal zone. Tracing of fibers in the subplate with DTI is unsuccessful due to the isotropy of this zone. Penetration of the cortical plate occurs after 24-26 PCW. In conclusion, frontal axonal pathways form the periventricular crossroads, sagittal strata and 'waiting' compartments during the path-finding and penetration of the cortical plate. Histochemistry is advantageous in the demonstration of a growth pattern, whereas DTI is unique for demonstrating axonal trajectories. The complexity of fibers is the biological substrate of selective vulnerability of the fetal white matter.

  17. Brain areas and pathways in the regulation of glucose metabolism.

    PubMed

    Diepenbroek, Charlene; Serlie, Mireille J; Fliers, Eric; Kalsbeek, Andries; la Fleur, Susanne E

    2013-01-01

    Glucose is the most important source of fuel for the brain and its concentration must be kept within strict boundaries to ensure the organism's optimal fitness. To maintain glucose homeostasis, an optimal balance between glucose uptake and glucose output is required. Besides managing acute changes in plasma glucose concentrations, the brain controls a daily rhythm in glucose concentrations. The various nuclei within the hypothalamus that are involved in the control of both these processes are well known. However, novel studies indicate an additional role for brain areas that are originally appreciated in other processes than glucose metabolism. Therefore, besides the classic hypothalamic pathways, we will review cortico-limbic brain areas and their role in glucose metabolism.

  18. Immunohistochemical localization of CB1 cannabinoid receptors in frontal cortex and related limbic areas in obese Zucker rats: effects of chronic fluoxetine treatment.

    PubMed

    Zarate, J; Churruca, I; Echevarría, E; Casis, L; López de Jesús, M; Saenz del Burgo, L; Sallés, J

    2008-10-21

    In the present study, we report on the application of two specific polyclonal antibodies to different intracellular domains of the CB1 cannabinoid receptor to define the expression of the neural CB1 cannabinoid receptor at the histochemical level in frontal cortex and related limbic areas of the obese Zucker rats. Higher levels of CB1 receptor expression in frontal, cingulated and piriform cortex, without differences in temporal, parietal and occipital cortex, were observed in obese Zucker rats, with respect to their lean littermates. CB1 phosphorylated receptor (CB1-P) levels were also higher in frontal, temporal, parietal and occipital cortex in obese rats with respect to lean controls. Potential involvement of brain cortical CB1 cannabinoid receptors in the long-term effects of fluoxetine was studied. Experimental animals were administered with fluoxetine (10 mg/kg, i.p.) daily for 3 weeks, whereas the control group was given 0.9% NaCl solution. In obese Zucker rats, a significant decrease in CB1 receptor levels, measured by western blot, was observed in brain cortex after fluoxetine treatment. Immunostaining for CB1 receptor expression was also carried out, showing a significant decrease in the density of neural cells positive for CB1 receptor in frontal, cingulate and piriform cortex, without changes in parietal, temporal and occipital regions. Regional prosencephalic immunostaining for CB1-P receptor level showed a significant decrease in the density of stained neural cells in frontal, temporal and parietal cortex, without changes in cingulated, piriform and occipital cortex. These results suggest the involvement of endocannabinoid system in the chronic effects of fluoxetine, especially in the frontal cortex.

  19. 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.

  20. Immunohistochemical localization of the D1 dopamine receptor in rat brain reveals its axonal transport, pre- and postsynaptic localization, and prevalence in the basal ganglia, limbic system, and thalamic reticular nucleus.

    PubMed Central

    Huang, Q; Zhou, D; Chase, K; Gusella, J F; Aronin, N; DiFiglia, M

    1992-01-01

    D1 dopamine receptor localization was examined by immunohistochemistry using a polyclonal anti-peptide antibody which (i) immunoprecipitated a protein fragment encoded by a D1 receptor cDNA and (ii) on Western blots of solubilized striatal and hippocampal membranes recognized two proteins of approximately 50 kDa and 75 kDa, corresponding to reported sizes of D1 receptor proteins. Immunoreactivity overlapped with dopamine-containing pathways, patterns of D1 receptor binding, and mRNA expression. Staining was concentrated in prefrontal, cingulate, parietal, piriform, entorhinal, and hippocampal cortical areas and subcortically in the basal ganglia, amygdala, septal area, substantia inominata, thalamus, hypothalamus, and neurohypophysis. Prominent labeling was seen in the thalamic reticular nucleus, a region known to integrate ascending basal forebrain inputs with thalamocortical and corticothalamic pathways and in fiber bundles interconnecting limbic areas. In striatal neuropil, staining appeared in spines (heads and necks), at postsynaptic sites in dendrites, and in axon terminals; in the pars reticulata of the substantia nigra, labeling was prevalent in myelinated and unmyelinated axons and dendrites. These data provide direct evidence for the regional and subcellular distribution of D1 receptor protein in the brain and for its pre- and postsynaptic localization in the basal ganglia. The prominent immunoreactivity seen in the limbic system and thalamic reticular nucleus supports an important role for this receptor subtype in mediating integrative processes involved with learning, memory, and cognition. Images PMID:1281547

  1. Estrogen in the limbic system.

    PubMed

    ter Horst, Gert J

    2010-01-01

    Estrogens are a group of steroid hormones that function as the primary female sex hormone. Estrogens not only have an important role in the regulation of the estrous or menstrual cycle but also control, for example, bone formation, the cardiovascular system, and cognitive functions. Estradiol (E2), the main representative of the group, is highly lipophylic and can easily pass the blood-brain barrier to modulate neuronal activity. Particularly the limbic system, a group of tightly interconnected forebrain areas controlling mood and emotion, is rich in estrogen receptors. To date two cytoplasmatic and/or nuclear estrogen receptors named ER-alpha (ERalpha) and ER-beta (ERbeta) have been identified. In the brain, ERalpha plays a critical role in regulating reproductive neuroendocrine behavior and function. ERbeta appears to play an important role in nonreproductive behaviors, such as learning and memory, anxiety, and mood. Five splice variants of ERbeta, named Erb1, Erb2, Erb1d3, Erb2d3, and Erb1d4, have been identified with possibly different biological activities. There is evidence of a thus far not definitely characterized membrane-linked ER receptor named mER-X. In this review, the anatomy of the limbic system and the distribution of estrogen receptors (ERs) are described in relation to coping with stress and the higher prevalence of stress-related psychiatric disorders in women. Effects of cyclic estrogen administration and chronic stress on recovery and neuronal plasticity are illustrated with own results. Copyright 2010 Elsevier Inc. All rights reserved.

  2. 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.

  3. Psychosurgery and the limbic system

    PubMed Central

    Kelly, Desmond

    1973-01-01

    The limbic system can be considered to consist of a central ‘core’ from which three well-defined circuits emerge. These are the Papez or medial circuit, the basolateral circuit and the defence reaction circuit. The functions of the primitive limbic brain are modulated by a higher order control—the frontal lobe. Emotional responses and physiological changes have been obtained by stimulation of fronto-limbic pathways and limbic circuits and these have been used for location of target sites in psychosurgery. For the relief of intractable depression and anxiety, lesions are generally made in the lower medial quadrant or posteroorbital part of the frontal lobe, where there is a concentration of fronto-limbic connections. In primary obsessional neurosis lesions at this site produce less satisfactory results, but these illnesses may be helped by lesions in the cingulate gyrus, which is part of the Papez circuit. Patients with epilepsy and aggressive outbursts may respond to temporal lobotomy, or to operations, such as amygdalotomy, where lesions are placed in the defence reaction circuit. PMID:4618902

  4. Limbic Correlates of Fearlessness and Disinhibition in Incarcerated Youth: Exploring the Brain-Behavior Relationship with the Psychopathy Checklist: Youth Version

    PubMed Central

    Walters, Glenn D.; Kiehl, Kent A.

    2015-01-01

    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. PMID:26363777

  5. Androgen-induced sexual dimorphism in high affinity dopamine binding in the brain transcends the hypothalamic-limbic region.

    PubMed Central

    Jalilian-Tehrani, M. H.; Karakiulakis, G.; Le Blond, C. B.; Powell, R.; Thomas, P. J.

    1982-01-01

    1 High affinity binding of [3H]-dopamine and [3H]-5-hydroxytryptamine ([3H]-5-HT) was measured in membrane fractions prepared from cerebral cortex, amygdala, hypothalamus, thalamus and brain stem of rats of either sex and of rats which had been either neonatally castrated or androgenized. 2 Binding was measured in rats of 8, 20 and 30 days old as well as in adults. 3 [3H]-dopamine bound with approximately 30 nM affinity ahd [3H]-5-HT with approximately 10 nM affinity to all areas of the brain tested. The relative inhibitory effects of haloperidol, apomorphine, cis-flupenthixol, unlabelled dopamine, noradrenaline, spiroperone, (+)-butaclamol, fluphenazine, pimozide and 5-HT on [3H]-dopamine binding in the cerebral cortex was consistent with receptor status for the binding components there as were the relative inhibitory effects of methysergide, dopamine, fluoxetine and ouabain on [3H]-5-HT binding in the fore brain. 4 Neither [3H]-dopamine nor [3H]-5-HT binding varied with the state of the sexual cycle in females. 5 There were no sexual differences in [3H]-5-HT binding in any of the brain areas tested nor was it affected by neonatal androgenization or neonatal castration. 6 [3H]-dopamine binding was greater in the cerebral cortex and amygdala of male than of female rats. These differences could be mimicked artificially by neonatal castration of males (female type development) or neonatal androgenization of females (male type development). Sexual dimorphism did not become overt until 20 days of age and did not extend to hypothalamus, thalamus or brain stem. 7 It is concluded that neonatal sex differences in exposure to steroid hormones has permanent effects on the number of dopamine binding sites in the cerebral cortex and is suggested that this sexual dimorphism extends to the amygdala. PMID:7074286

  6. Amphetamine Withdrawal Differentially Increases the Expression of Organic Cation Transporter 3 and Serotonin Transporter in Limbic Brain Regions

    PubMed Central

    Solanki, Rajeshwari R.; Scholl, Jamie L.; Watt, Michael J.; Renner, Kenneth J.; Forster, Gina L.

    2016-01-01

    Amphetamine withdrawal increases anxiety and stress sensitivity related to blunted ventral hippocampus (vHipp) and enhances the central nucleus of the amygdala (CeA) serotonin responses. Extracellular serotonin levels are regulated by the serotonin transporter (SERT) and organic cation transporter 3 (OCT3), and vHipp OCT3 expression is enhanced during 24 hours of amphetamine withdrawal, while SERT expression is unaltered. Here, we tested whether OCT3 and SERT expression in the CeA is also affected during acute withdrawal to explain opposing regional alterations in limbic serotonergic neurotransmission and if respective changes continued with two weeks of withdrawal. We also determined whether changes in transporter expression were confined to these regions. Male rats received amphetamine or saline for two weeks followed by 24 hours or two weeks of withdrawal, with transporter expression measured using Western immunoblot. OCT3 and SERT expression increased in the CeA at both withdrawal timepoints. In the vHipp, OCT3 expression increased only at 24 hours of withdrawal, with an equivalent pattern seen in the dorsomedial hypothalamus. No changes were evident in any other regions sampled. These regionally specific changes in limbic OCT3 and SERT expression may partially contribute to the serotonergic imbalance and negative affect during amphetamine withdrawal. PMID:27478387

  7. Amphetamine Withdrawal Differentially Increases the Expression of Organic Cation Transporter 3 and Serotonin Transporter in Limbic Brain Regions.

    PubMed

    Solanki, Rajeshwari R; Scholl, Jamie L; Watt, Michael J; Renner, Kenneth J; Forster, Gina L

    2016-01-01

    Amphetamine withdrawal increases anxiety and stress sensitivity related to blunted ventral hippocampus (vHipp) and enhances the central nucleus of the amygdala (CeA) serotonin responses. Extracellular serotonin levels are regulated by the serotonin transporter (SERT) and organic cation transporter 3 (OCT3), and vHipp OCT3 expression is enhanced during 24 hours of amphetamine withdrawal, while SERT expression is unaltered. Here, we tested whether OCT3 and SERT expression in the CeA is also affected during acute withdrawal to explain opposing regional alterations in limbic serotonergic neurotransmission and if respective changes continued with two weeks of withdrawal. We also determined whether changes in transporter expression were confined to these regions. Male rats received amphetamine or saline for two weeks followed by 24 hours or two weeks of withdrawal, with transporter expression measured using Western immunoblot. OCT3 and SERT expression increased in the CeA at both withdrawal timepoints. In the vHipp, OCT3 expression increased only at 24 hours of withdrawal, with an equivalent pattern seen in the dorsomedial hypothalamus. No changes were evident in any other regions sampled. These regionally specific changes in limbic OCT3 and SERT expression may partially contribute to the serotonergic imbalance and negative affect during amphetamine withdrawal.

  8. Effects of Forced Swimming Stress on ERK and Histone H3 Phosphorylation in Limbic Areas of Roman High- and Low-Avoidance Rats

    PubMed Central

    Piludu, Maria Antonietta; Poddighe, Laura; Serra, Maria Pina; Quartu, Marina; Corda, Maria Giuseppa; Giorgi, Osvaldo

    2017-01-01

    Stressful events evoke molecular adaptations of neural circuits through chromatin remodeling and regulation of gene expression. However, the identity of the molecular pathways activated by stress in experimental models of depression is not fully understood. We investigated the effect of acute forced swimming (FS) on the phosphorylation of the extracellular signal-regulated kinase (ERK)1/2 (pERK) and histone H3 (pH3) in limbic brain areas of genetic models of vulnerability (RLA, Roman low-avoidance rats) and resistance (RHA, Roman high-avoidance rats) to stress-induced depression-like behavior. We demonstrate that FS markedly increased the density of pERK-positive neurons in the infralimbic (ILCx) and the prelimbic area (PrLCx) of the prefrontal cortex (PFCx), the nucleus accumbens, and the dorsal blade of the hippocampal dentate gyrus to the same extent in RLA and RHA rats. In addition, FS induced a significant increase in the intensity of pERK immunoreactivity (IR) in neurons of the PFCx in both rat lines. However, RHA rats showed stronger pERK-IR than RLA rats in the ILCx both under basal and stressed conditions. Moreover, the density of pH3-positive neurons was equally increased by FS in the PFCx of both rat lines. Interestingly, pH3-IR was higher in RHA than RLA rats in PrLCx and ILCx, either under basal conditions or upon FS. Finally, colocalization analysis showed that in the PFCx of both rat lines, almost all pERK-positive cells express pH3, whereas only 50% of the pH3-positive neurons is also pERK-positive. Moreover, FS increased the percentage of neurons that express exclusively pH3, but reduced the percentage of cells expressing exclusively pERK. These results suggest that (i) the distinctive patterns of FS-induced ERK and H3 phosphorylation in the PFCx of RHA and RLA rats may represent molecular signatures of the behavioural traits that distinguish the two lines and (ii) FS-induced H3 phosphorylation is, at least in part, ERK-independent. PMID:28107383

  9. Delta FosB and AP-1-mediated transcription modulate cannabinoid CB₁ receptor signaling and desensitization in striatal and limbic brain regions.

    PubMed

    Lazenka, Matthew F; David, Bethany G; Lichtman, Aron H; Nestler, Eric J; Selley, Dana E; Sim-Selley, Laura J

    2014-10-01

    Repeated Δ(9)-tetrahydrocannabinol (THC) administration produces cannabinoid type 1 receptor (CB₁R) desensitization and downregulation, as well as tolerance to its in vivo pharmacological effects. However, the magnitude of CB₁R desensitization varies by brain region, with CB₁Rs in the striatum and its output nuclei undergoing less desensitization than other regions. A growing body of data indicates that regional differences in CB₁R desensitization are produced, in part, by THC-mediated induction of the stable transcription factor, ΔFosB, and subsequent regulation of CB₁Rs. The purpose of the present study was to determine whether THC-mediated induction of ΔFosB in the striatum inhibits CB₁R desensitization in the striatum and output nuclei. This hypothesis was tested using bitransgenic mice with inducible expression of ΔFosB or ΔcJun, a dominant negative inhibitor of AP-1-mediated transcription, in specific forebrain regions. Mice were treated repeatedly with escalating doses of THC or vehicle for 6.5 days, and CB₁R-mediated G-protein activation was assessed using CP55,940-stimulated [(35)S]GTPγS autoradiography. Overexpression of ΔFosB in striatal dopamine type 1 receptor-containing (D1R) medium spiny neurons (MSNs) attenuated CB₁R desensitization in the substantia nigra, ventral tegmental area (VTA) and amygdala. Expression of ΔcJun in striatal D1R- and dopamine type 2 receptor (D2R)-containing MSNs enhanced CB₁R desensitization in the caudate-putamen and attenuated desensitization in the hippocampus and VTA. THC-mediated in vivo pharmacological effects were then assessed in ΔcJun-expressing mice. Tolerance to THC-mediated hypomotility was enhanced in ΔcJun-expressing mice. These data reveal that ΔFosB and possibly other AP-1 binding proteins regulate CB₁R signaling and adaptation in the striatum and limbic system. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Limbic Interference During Social Action Planning in Schizophrenia.

    PubMed

    Stegmayer, Katharina; Bohlhalter, Stephan; Vanbellingen, Tim; Federspiel, Andrea; Wiest, Roland; Müri, René M; Strik, Werner; Walther, Sebastian

    2017-05-30

    Schizophrenia is characterized by social interaction deficits contributing to poor functional outcome. Hand gesture use is particularly impaired, linked to frontal lobe dysfunction and frontal grey matter deficits. The functional neural correlates of impaired gesturing are currently unclear. We therefore investigated aberrant brain activity during impaired gesturing in schizophrenia. We included 22 patients with schizophrenia and 25 healthy control participants matched for age, gender, and education level. We obtained functional magnetic resonance imaging data using an event-related paradigm to assess brain activation during gesture planning and execution. Group differences in whole brain effects were calculated using factorial designs. Gesture ratings were performed by a single rater, blind to diagnoses and clinical presentation. During gesture planning and execution both groups activated brain areas of the praxis network. However, patients had reduced dorsolateral prefrontal cortex (DLPFC) and increased inferior parietal lobe (IPL) activity. Performance accuracy was associated with IPL activity in patients. Furthermore, patients activated temporal poles, amygdala and hippocampus during gesture planning, which was associated with delusion severity. Finally, patients demonstrated increased dorsomedial prefrontal cortex activity during planning of novel gestures. We demonstrate less prefrontal, but more IPL and limbic activity during gesturing in schizophrenia. IPL activity was associated with performance accuracy, whereas limbic activity was linked to delusion severity. These findings may reflect impaired social action planning and a limbic interference with gestures in schizophrenia contributing to poor gesture performance and consequently poor social functioning in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  11. Connections of the limbic network: a corticocortical evoked potentials study.

    PubMed

    Enatsu, Rei; Gonzalez-Martinez, Jorge; Bulacio, Juan; Kubota, Yuichi; Mosher, John; Burgess, Richard C; Najm, Imad; Nair, Dileep R

    2015-01-01

    Papez proposed a network for higher brain function, which is termed the limbic network. However, the in vivo human limbic network has not been established. We investigated the connectivity of the human limbic system using corticocortical evoked potential (CCEP). This retrospective analysis included 28 patients with medically intractable focal epilepsy who underwent stereoelectroencephalography (SEEG) and CCEP. Alternating 1 Hz electrical stimuli were delivered to parts of the limbic system [anterior and posterior hippocampus, temporal pole, parahippocampal gyrus (PHG), amygdala, anterior (ACG) and posterior cingulate gyrus (PCG), medial and lateral orbitofrontal cortex (OF)]. A total of 40-60 stimuli were averaged in each trial to obtain CCEP responses. CCEP distributions were evaluated by calculating the root mean square (RMS) of CCEP responses. Anterior hippocampal stimulation elicited prominent CCEP responses in medial and lateral temporal structures, PCG, medial OF and insula over the ipsilateral hemisphere. Posterior hippocampal stimulation induced CCEP responses in the ipsilateral medial and lateral temporal structures and PCG. The findings also revealed connections from temporal pole to the ipsilateral medial temporal structures, and connections from PHG to the ipsilateral hippocampus and PCG. The amygdala projected to broad areas including the ipsilateral medial and lateral temporal structures, medial and lateral frontal areas, the cingulate gyrus, insula and inferior parietal lobule. ACG and PCG showed connections to the ipsilateral medial fronto-parietal areas and connections to bilateral medial temporo-parieto-occipital and lateral parieto-occipital areas, respectively. Medial and lateral OF stimulation induced responses in the adjacent cortices. This study revealed that various regions within the limbic network are intimately connected in reverberating circuits and are linked to specific ipsilateral and contralateral regions, which may reflect

  12. Cortico-subthalamic inputs from the motor, limbic, and associative areas in normal and dopamine-depleted rats are not fully segregated.

    PubMed

    Janssen, Marcus L F; Temel, Yasin; Delaville, Claire; Zwartjes, Daphne G M; Heida, Tjitske; De Deurwaerdère, Philippe; Visser-Vandewalle, Veerle; Benazzouz, Abdelhamid

    2017-08-01

    The subthalamic nucleus (STN) receives monosynaptic glutamatergic afferents from different areas of the cortex, known as the "hyperdirect" pathway. The STN has been divided into three distinct subdivisions, motor, limbic, and associative parts in line with the concept of parallel information processing. The extent to which the parallel information processing coming from distinct cortical areas overlaps in the different territories of the STN is still a matter of debate and the proposed role of dopaminergic neurons in maintaining the coherence of responses to cortical inputs in each territory is not documented. Using extracellular electrophysiological approaches, we investigated to what degree the motor and non-motor regions in the STN are segregated in control and dopamine (DA) depleted rats. We performed electrical stimulation of different cortical areas and recorded STN neuronal responses. We showed that motor and non-motor cortico-subthalamic pathways are not fully segregated, but partially integrated in the rat. This integration was mostly present through the indirect pathway. The spatial distribution and response latencies were the same in sham and 6-hydroxydopamine lesioned animals. The inhibitory phase was, however, less apparent in the lesioned animals. In conclusion, this study provides the first evidence that motor and non-motor cortico-subthalamic pathways in the rat are not fully segregated, but partially integrated. This integration was mostly present through the indirect pathway. We also show that the inhibitory phase induced by GABAergic inputs from the external segment of the globus pallidus is reduced in the DA-depleted animals.

  13. Repeated unpredictable stress and antidepressants differentially regulate expression of the bcl-2 family of apoptotic genes in rat cortical, hippocampal, and limbic brain structures.

    PubMed

    Kosten, Therese A; Galloway, Matthew P; Duman, Ronald S; Russell, David S; D'Sa, Carrol

    2008-06-01

    Apoptosis has been proposed as a contributing cellular mechanism to the structural alterations that have been observed in stress-related mood disorders. Antidepressants, on the other hand, are hypothesized to exert trophic and/or neuroprotective actions. The present study examined the regulation of the major antiapoptotic (Bcl-2, Bcl-xl) and proapoptotic (Bax) genes by repeated unpredictable stress (an animal model of depression) and antidepressant treatments (ADT). In adult rats, exposure to unpredictable stress reduced Bcl-2 mRNA levels in the central nucleus of the amygdala (CeA), cingulate (Cg), and frontal (Fr) cortices. Bcl-xl mRNA was significantly decreased in hippocampal subfields. In contrast, chronic administration of clinically effective antidepressants from four different classes, ie fluoxetine, reboxetine, tranylcypromine, and electroconvulsive seizures (ECS) upregulated Bcl-2 mRNA expression in the Cg, Fr, and CeA. Reboxetine, tranylcypromine, and ECS selectively increased Bcl-xl, but not Bcl-2 mRNA expression in the hippocampus. Chemical ADT but not ECS, robustly enhanced Bcl-2 expression in the medial amygdaloid nucleus and ventromedial hypothalamus. Fluoxetine did not influence Bcl-xl expression in the hippocampus, but it was the only ADT that decreased Bax expression in this region. In the CeA, again in direct contrast to the stress effects, exposure to all classes of ADTs significantly increased Bcl-2 mRNA. The selective regulation of Bcl-xl and Bax in hippocampal subfields and of Bcl-2 in the Cg cortex, amygdala, and hypothalamus suggests that these cellular adaptations contribute to the long-term neural plastic adaptations to stress and ADTs in cortical, hypothalamic, and limbic brain structures.

  14. A variant on the kappa opioid receptor gene (OPRK1) is associated with stress response and related drug craving, limbic brain activation and cocaine relapse risk.

    PubMed

    Xu, K; Seo, D; Hodgkinson, C; Hu, Y; Goldman, D; Sinha, R

    2013-08-20

    Stress increases drug craving and relapse risk. The kappa opioid receptor gene (OPRK1) mediates stress responses. Here, we examined whether the OPRK1 rs6989250 C>G affects stress-induced cocaine craving and cortisol responses, subsequent cocaine relapse risk and the neural response to stress using functional magnetic resonance imaging (fMRI) in cocaine dependence. Sixty-seven treatment-engaged, abstinent cocaine-dependent African-Americans were genotyped (CG: N=10; CC: N=57) and participated in a 3-day experiment in which they were exposed to personalized script-driven imagery of stress, drug cues and neutral scenarios, one condition per day, randomly assigned and counterbalanced across subjects. Repeated measures of craving and cortisol were obtained. The subjects were followed prospectively for 90 days to assess relapse risk. A follow-up preliminary fMRI experiment assessed neural responses to stress, drug cue and neutral conditions in matched CG (N=5) and CC (N=8) subgroups. We found greater stress-induced craving (P=0.019), higher cortisol during stress and cue relative to the neutral condition (P's<0.003), and increased cocaine relapse risk (P=0.0075) in the CG compared with the CC group. The CG relative to the CC group also showed greater activation of limbic and midbrain regions during stress and cues relative to the neutral condition with additional stress-induced activation in the right amygdala/hippocampus (P<0.05, whole-brain corrected). These results suggest that OPRK1 is associated with stress-induced craving and cortisol, hyperactive hypothalamus/thalamus-midbrain-cerebellum responses, and also associated with greater subsequent cocaine relapse risk. Future studies to replicate these findings in a larger sample size are warranted.

  15. Seronegative Paraneoplastic Limbic Encephalitis Associated with Thymoma.

    PubMed

    Toro, Jaime; Cuellar-Giraldo, David; Duque, Alejandra; Minota, Karla; Patiño, Jorge; García, Manuel

    2017-09-01

    Paraneoplastic limbic encephalitis is an autoimmune syndrome characterized by the acute or subacute onset of encephalopathy, memory loss, confusion, temporal lobe seizures, and behavioral and mood changes. Although most patients with paraneoplastic limbic encephalitis have antineuronal antibodies, advances in the field now permit the diagnosis without autoantibody test results. In this case illustrating the new diagnostic criteria, we report a 70-year-old woman who was brought to the emergency room after the acute onset of cognitive impairment, altered mental status, and choreoathetoid movements. Brain magnetic resonance imaging showed hyperintense signals in both temporal lobes, and a chest computed tomogram revealed a thymoma. Because the patient met current diagnostic criteria for autoimmune limbic encephalitis, we were able to start treatment before her antibody tests were processed. The patient received immunotherapy and her tumor was resected. Her choreoathetoid movements disappeared and her other neurologic symptoms improved. Her cerebrospinal fluid proved to be negative for paraneoplastic limbic encephalitis antibodies. Most but not all patients with paraneoplastic limbic encephalitis associated with thymoma have evidence of paraneoplastic antibodies. Prompt management of the underlying malignancy determines whether patients survive and may minimize future cognitive and functional impairment. Practicing neurologists and psychiatrists should be aware of this diagnosis.

  16. Uppermost synchronized generators of spike-wave activity are localized in limbic cortical areas in late-onset absence status epilepticus.

    PubMed

    Piros, Palma; Puskas, Szilvia; Emri, Miklos; Opposits, Gabor; Spisak, Tamas; Fekete, Istvan; Clemens, Bela

    2014-03-01

    Absence status (AS) epilepticus with generalized spike-wave pattern is frequently found in severely ill patients in whom several disease states co-exist. The cortical generators of the ictal EEG pattern and EEG functional connectivity (EEGfC) of this condition are unknown. The present study investigated the localization of the uppermost synchronized generators of spike-wave activity in AS. Seven patients with late-onset AS were investigated by EEG spectral analysis, LORETA (Low Resolution Electromagnetic Tomography) source imaging, and LSC (LORETA Source Correlation) analysis, which estimates cortico-cortical EEGfC among 23 ROIs (regions of interest) in each hemisphere. All the patients showed generalized ictal EEG activity. Maximum Z-scored spectral power was found in the 1-6 Hz and 12-14 Hz frequency bands. LORETA showed that the uppermost synchronized generators of 1-6 Hz band activity were localized in frontal and temporal cortical areas that are parts of the limbic system. For the 12-14 Hz band, abnormally synchronized generators were found in the antero-medial frontal cortex. Unlike the rather stereotyped spectral and LORETA findings, the individual EEGfC patterns were very dissimilar. The findings are discussed in the context of nonconvulsive seizure types and the role of the underlying cortical areas in late-onset AS. The diversity of the EEGfC patterns remains an enigma. Localizing the cortical generators of the EEG patterns contributes to understanding the neurophysiology of the condition. Copyright © 2013 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  17. Neuropathology of the limbic system.

    PubMed

    Shaw, C M; Alvord, E C

    1997-02-01

    The history and development of the fanciful terminology concerning the structures of the limbic system are discussed. The diseases involving the limbic system are divided into three groups; (1) diseases in which the limbic system is more or less selectively involved, such as limbic encephalitis, herpes simplex encephalitis, cerebral confusions by the falx and tentorium, and internal herniations through the falx and tentorium; (2) diseases in which the limbic system is predominantly involved, such as arhinencephalia, holoprosencephaly, cyst of cavum septi pellucidi, Pick's disease, Alzheimer's disease, hippocampal sclerosis, and vascular diseases of the hippocampal formation; and (3) diseases in which the limbic system is randomly involved, such as various types of neoplasms and vascular and inflammatory lesions. The relationship between destructive lesions of the hippocampus and memory also is emphasized.

  18. Bilateral limbic system destruction in man.

    PubMed

    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.

  19. 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

  20. Limbic but not non-limbic kindling impairs conditioned fear and promotes plasticity of NPY and its Y2 receptor.

    PubMed

    Botterill, J J; Guskjolen, A J; Marks, W N; Caruncho, H J; Kalynchuk, L E

    2015-11-01

    Epileptic seizures negatively affect cognition. However, the mechanisms that contribute to cognitive impairments after seizures are largely unknown. Here, we examined the effects of long-term kindling (i.e., 99 stimulations) of limbic (basolateral amygdala, dorsal hippocampus) and non-limbic (caudate nucleus) brain sites on conditioned fear and hippocampal plasticity. We first showed that kindling had no effect on acquisition of a hippocampal-dependent trace fear-conditioning task but limbic kindling impaired the retrieval of these fear memories. To determine the relationship between memory and hippocampal neuronal activity, we examined the expression of Fos protein 90 min after memory retrieval (i.e., 4 days after the last kindling stimulation). We found that limbic kindling, but not non-limbic kindling, decreased Fos expression in the granule cell layer, hilus, CA3 pyramidal cell layer, and CA1 pyramidal cell layer. Next, to investigate a mechanism that could contribute to dampen hippocampal neuronal activity in limbic-kindled rats, we focused on the endogenous anticonvulsant neuropeptide Y (NPY), which is expressed in a subset of GABAergic interneurons and can prevent glutamate release through interactions with its Y2 receptor. We found that limbic kindling significantly decreased the number of NPY-immunoreactive cells in several hippocampal subfields despite minimal staining of the neurodegenerative marker Fluoro-Jade B. However, we also noted that limbic kindling enhanced NPY immunoreactivity throughout the mossy fiber pathway. In these same regions, we observed limbic kindling-induced de novo expression of the NPY Y2 receptor. These novel findings demonstrate the site-specific effects of kindling on cognition and NPY plasticity, and they provide evidence that altered hippocampal NPY after limbic seizures coincides with dampened neural activity and cognitive impairments.

  1. Connections of the macaque Granular Frontal Opercular (GrFO) area: a possible neural substrate for the contribution of limbic inputs for controlling hand and face/mouth actions.

    PubMed

    Gerbella, Marzio; Borra, Elena; Rozzi, Stefano; Luppino, Giuseppe

    2016-01-01

    We traced the connections of the macaque Granular Frontal Opercular (GrFO) area, located in the rostralmost part of the frontal opercular margin, and compared them with those of the caudally adjacent dorsal opercular (DO) and precentral opercular (PrCO) areas. Area GrFO displays strong connections with areas DO, PrCO, and ventrolateral prefrontal (VLPF) area 12l, and even more with the mostly hand-related ventral premotor (PMv) area F5a. Other connections involve the mostly face/mouth-related PMv area F5c, the arm-related area F6/pre-SMA, the hand-related fields of VLPF areas 46v and 12r, and area SII, mostly the hand representation. Furthermore, area GrFO shows rich connectivity with several components of the limbic system including orbitofrontal areas 12o, 12m, and 11, the agranular and dysgranular insula, the agranular cingulate area 24, and the amygdala. Thalamic afferents originate primarily from the parvocellular and the magnocellular subdivisions of the mediodorsal nucleus and from midline and intralaminar nuclei. This connectivity pattern clearly distinguishes area GrFO from areas DO and PrCO, characterized by a connectivity mostly involving oral sensorimotor and gustatory areas/subcortical structures. The present data suggest, based on connectivity patterns, an involvement of area GrFO in the cortical circuits for controlling goal-directed hand and face/mouth actions. In this context, area GrFO could represent a gateway for the access of limbic inputs, for example about subjective values, emotional significance of stimuli or internal states, to the PMv areas involved in selecting appropriate goal-directed hand and mouth/face actions.

  2. Lesion analysis for cingulotomy and limbic leucotomy: comparison and correlation with clinical outcomes

    PubMed Central

    Yang, Jimmy C.; Ginat, Daniel T.; Dougherty, Darin D.

    2014-01-01

    Object Cingulotomy and limbic leucotomy are lesioning surgeries with demonstrated benefit for medically intractable psychiatric illnesses. They represent significant refinements of the prefrontal lobotomy used from the 1930s through the 1950s. However, the associations between anatomical characterization of these lesions and outcome data are not well understood. To elucidate these procedures and associations, the authors sought to define and compare the neuroanatomy of cingulotomy and limbic leucotomy and to test a method that uses neuroanatomical data and voxel-based lesion–symptom mapping (VLSM) to reveal potential refinements to modern psychiatric neurosurgical procedures. Methods T1-weighted MR images of patients who had undergone cingulotomy and limbic leucotomy were segmented and registered onto the Montreal Neurological Institute T1-weighted template brain MNI152. Using an atlas-based approach, the authors calculated, by case, the percentage of each anatomical structure affected by the lesion. Because of the infrequency of modern lesion procedures and the requirement for higher-resolution clinical imaging, the sample size was small. The pilot study correlated cingulotomy and limbic leucotomy lesion characteristics with clinical outcomes for patients with obsessive-compulsive disorder. For this study, preoperative and postoperative Yale-Brown Obsessive Compulsive Scale scores for 11 cingulotomy patients and 8 limbic leucotomy patients were obtained, and lesion masks were defined and compared anatomically by using an atlas-based method. Statistically significant voxels were additionally calculated by using VLSM techniques that correlated lesion characteristics with postoperative scores. Results Mean lesion volumes were 13.3 ml for cingulotomy and 11.8 ml for limbic leucotomy. As expected, cingulotomy was isolated to the anterior cingulum. The subcaudate tractotomy portion of limbic leucotomy additionally affected Brodmann area 25, the medial orbitofrontal

  3. Intracranial Metastatic Disease Spares the Limbic Circuit: A Review of 697 Metastatic Lesions in 107 Patients

    SciTech Connect

    Marsh, James C.; Herskovic, Arnold M.; Gielda, Benjamin T.; Hughes, Frank F.; Hoeppner, Thomas; Turian, Julius; Abrams, Ross A.

    2010-02-01

    Purpose: We report the incidence of metastatic involvement of the limbic circuit in a retrospective review of patients treated at our institution. This review was performed to assess the feasibility of selectively sparing the limbic system during whole-brain radiotherapy and prophylactic cranial irradiation. Methods and Materials: We identified 697 intracranial metastases in 107 patients after reviewing contrast-enhanced CT and/or MR image sets for each patient. Lesions were localized to the limbic circuit or to the rest of the brain/brain stem. Patients were categorized by tumor histology (e.g., non-small-cell lung cancer, small-cell lung cancer, breast cancer, and other) and by total number of intracranial metastases (1-3, oligometastatic; 4 or more, nonoligometastatic). Results: Thirty-six limbic metastases (5.2% of all metastases) were identified in 22 patients who had a median of 16.5 metastases/patient (limbic metastases accounted for 9.9% of their lesions). Sixteen metastases (2.29%) involved the hippocampus, and 20 (2.86%) involved the rest of the limbic circuit; 86.2% of limbic metastases occurred in nonoligometastatic patients, and 13.8% occurred in oligometastatic patients. The incidence of limbic metastases by histologic subtype was similar. The incidence of limbic metastases in oligometastatic patients was 4.9% (5/103): 0.97%, hippocampus; 3.9%, remainder of the limbic circuit. One of 53 oligometastatic patients (1.9%) had hippocampal metastases, while 4/53 (7.5%) had other limbic metastases. Conclusions: Metastatic involvement of the limbic circuit is uncommon and limited primarily to patients with nonoligometastatic disease, supporting our hypothesis that it is reasonable to selectively exclude or reduce the dose to the limbic circuit when treating patients with prophylactic cranial irradiation or whole-brain radiotherapy for oligometastatic disease not involving these structures.

  4. Chronic intermittent ethanol exposure and withdrawal alters (3α,5α)-3-hydroxy-pregnan-20-one immunostaining in cortical and limbic brain regions of C57BL/6J mice

    PubMed Central

    Maldonado-Devincci, Antoniette M.; Cook, Jason B.; O'Buckley, Todd K.; Morrow, Danielle H.; McKinley, Raechel E.; Lopez, Marcelo F.; Becker, Howard C.; Morrow, A. Leslie

    2014-01-01

    Background The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP, allopregnanolone) has been studied during withdrawal from ethanol in humans, rats and mice. Serum 3α,5α-THP levels decreased and brain levels were not altered following acute ethanol administration (2 g/kg) in male C57BL/6J mice, however the effects of chronic intermittent ethanol (CIE) exposure on 3α,5α-THP levels have not been examined. Given that CIE exposure changes subsequent voluntary ethanol drinking in a time-dependent fashion following repeated cycles of ethanol exposure, we conducted a time-course analysis of CIE effects on 3α,5α-THP levels in specific brain regions known to influence drinking behavior. Methods Adult male C57BL/6J mice were exposed to four cycles of CIE to induce ethanol dependence. All mice were sacrificed and perfused at one of two time points, 8 hr or 72 hr following the final exposure cycle. Free floating brain sections (40 μm; 3-5 sections/region/animal) were immunostained and analyzed to determine relative levels of cellular 3α,5α-THP. Results Withdrawal from CIE exposure produced time-dependent and region-specific effects on immunohistochemical detection of 3α,5α-THP levels across cortical and limbic brain regions. A transient reduction in 3α,5α-THP immunoreactivity was observed in the central nucleus of the amygdala 8 hr after withdrawal from CIE (-31.4 ± 9.3). Decreases in 3α,5α-THP immunoreactivity were observed 72 hr following withdrawal in the medial prefrontal cortex (−25.0 ± 9.3%), nucleus accumbens core (−29.9 ± 6.6%), and dorsolateral striatum (−18.5 ± 6.0%), while an increase was observed in the CA3 pyramidal cell layer of the hippocampus (+42.8 ± 19.5%). Sustained reductions in 3α,5α-THP immunoreactivity were observed at both time points in the lateral amygdala (8 hr −28.3 ± 12.8%; 72 hr −27.5 ± 12.4%) and in the ventral tegmental area (8 hr −26.5 ± 9.9%; 72 hr −31.6 ± 13.8%). Conclusions

  5. Chronic intermittent ethanol exposure and withdrawal alters (3α,5α)-3-hydroxy-pregnan-20-one immunostaining in cortical and limbic brain regions of C57BL/6J mice.

    PubMed

    Maldonado-Devincci, Antoniette M; Cook, Jason B; O'Buckley, Todd K; Morrow, Danielle H; McKinley, Raechel E; Lopez, Marcelo F; Becker, Howard C; Morrow, A Leslie

    2014-10-01

    The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP; allopregnanolone) has been studied during withdrawal from ethanol (EtOH) in humans, rats, and mice. Serum 3α,5α-THP levels decreased, and brain levels were not altered following acute EtOH administration (2 g/kg) in male C57BL/6J mice; however, the effects of chronic intermittent ethanol (CIE) exposure on 3α,5α-THP levels have not been examined. Given that CIE exposure changes subsequent voluntary EtOH drinking in a time-dependent fashion following repeated cycles of EtOH exposure, we conducted a time-course analysis of CIE effects on 3α,5α-THP levels in specific brain regions known to influence drinking behavior. Adult male C57BL/6J mice were exposed to 4 cycles of CIE to induce EtOH dependence. All mice were sacrificed and perfused at 1 of 2 time points, 8 or 72 hours following the final exposure cycle. Free-floating brain sections (40 μm; 3 to 5 sections/region/animal) were immunostained and analyzed to determine relative levels of cellular 3α,5α-THP. Withdrawal from CIE exposure produced time-dependent and region-specific effects on immunohistochemical detection of 3α,5α-THP levels across cortical and limbic brain regions. A transient reduction in 3α,5α-THP immunoreactivity was observed in the central nucleus of the amygdala 8 hours after withdrawal from CIE (-31.4 ± 9.3%). Decreases in 3α,5α-THP immunoreactivity were observed 72 hours following withdrawal in the medial prefrontal cortex (-25.0 ± 9.3%), nucleus accumbens core (-29.9 ± 6.6%), and dorsolateral striatum (-18.5 ± 6.0%), while an increase was observed in the CA3 pyramidal cell layer of the hippocampus (+42.8 ± 19.5%). Sustained reductions in 3α,5α-THP immunoreactivity were observed at both time points in the lateral amygdala (8 hours -28.3 ± 12.8%; 72 hours -27.5 ± 12.4%) and in the ventral tegmental area (8 hours -26.5 ± 9.9%; 72 hours -31.6 ± 13.8%). These data

  6. Constrained spherical deconvolution analysis of the limbic network in human, with emphasis on a direct cerebello-limbic pathway

    PubMed Central

    Arrigo, Alessandro; Mormina, Enricomaria; Anastasi, Giuseppe Pio; Gaeta, Michele; Calamuneri, Alessandro; Quartarone, Angelo; De Salvo, Simona; Bruschetta, Daniele; Rizzo, Giuseppina; Trimarchi, Fabio; Milardi, Demetrio

    2014-01-01

    The limbic system is part of an intricate network which is involved in several functions like memory and emotion. Traditionally the role of the cerebellum was considered mainly associated to motion control; however several evidences are raising about a role of the cerebellum in learning skills, emotions control, mnemonic and behavioral processes involving also connections with limbic system. In 15 normal subjects we studied limbic connections by probabilistic Constrained Spherical Deconvolution (CSD) tractography. The main result of our work was to prove for the first time in human brain the existence of a direct cerebello-limbic pathway which was previously hypothesized but never demonstrated. We also extended our analysis to the other limbic connections including cingulate fasciculus, inferior longitudinal fasciculus, uncinated fasciculus, anterior thalamic connections and fornix. Although these pathways have been already described in the tractographic literature we provided reconstruction, quantitative analysis and Fractional Anisotropy (FA) right-left symmetry comparison using probabilistic CSD tractography that is known to provide a potential improvement compared to previously used Diffusion Tensor Imaging (DTI) techniques. The demonstration of the existence of cerebello-limbic pathway could constitute an important step in the knowledge of the anatomic substrate of non-motor cerebellar functions. Finally the CSD statistical data about limbic connections in healthy subjects could be potentially useful in the diagnosis of pathological disorders damaging this system. PMID:25538606

  7. Heritability of the limbic networks

    PubMed Central

    Kawadler, Jamie M.; Dell'Acqua, Flavio; Rijsdijk, Frühling V.; Kane, Fergus; Picchioni, Marco; McGuire, Philip; Toulopoulou, Timothea; Georgiades, Anna; Kalidindi, Sridevi; Kravariti, Eugenia; Murray, Robin M.; Murphy, Declan G.; Craig, Michael C.; Catani, Marco

    2016-01-01

    Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins. We explored the connections that contribute to the activity of three distinct functional limbic networks, namely the dorsal cingulum (‘medial default-mode network’), the ventral cingulum and the fornix (‘hippocampal-diencephalic-retrosplenial network’) and the uncinate fasciculus (‘temporo-amygdala-orbitofrontal network’). Genetic and environmental variances were mapped for multiple tract-specific measures that reflect different aspects of the underlying anatomy. We report the highest heritability for the uncinate fasciculus, a tract that underpins emotion processing, semantic cognition, and social behaviour. High to moderate genetic and shared environmental effects were found for pathways important for social behaviour and memory, for example, fornix, dorsal and ventral cingulum. These findings indicate that within the limbic system inheritance of specific traits may rely on the anatomy of distinct networks and is higher for fronto-temporal pathways dedicated to complex social behaviour and emotional processing. PMID:26714573

  8. Brain areas involved in synaesthesia: a review.

    PubMed

    Rouw, Romke; Scholte, H Steven; Colizoli, Olympia

    2011-09-01

    Despite a recent upsurge of research, much remains unknown about the neurobiological mechanisms underlying synaesthesia. By integrating results obtained so far in Magnetic Resonance Imaging (MRI) studies, this contribution sheds light on the role of particular brain regions in synaesthetic experiences. First, in accordance with its sensory nature, it seems that the sensory brain areas corresponding to the type of synaesthetic experience are activated. Synaesthetic colour experiences can activate colour regions in occipito-temporal cortex, but this is not necessarily restricted to V4. Furthermore, sensory and motor brain regions have been obtained that extend beyond the particular type of synaesthesia studied. Second, differences in experimental setup, number and type of synaesthetes tested, and method to delineate regions of interest may help explain inconsistent results obtained in the BOLD-MRI (Blood Oxygen Level Dependent functional MRI) studies. Third, an overview of obtained results shows that a network of brain areas rather than a single brain region underlies synaesthesia. Six brain regions of overlapping results emerge, these regions are in sensory and motor regions as well as 'higher level' regions in parietal and frontal lobe. We propose that these regions are related to three different cognitive processes inherently part of synaesthesia; the sensory processes, the (attentional) 'binding' processes, and cognitive control processes. Finally, we discuss how these functional and structural brain properties might relate to the development of synaesthesia. In particular, we believe this relationship is better understood by separating the question what underlies the presence of synaesthesia ('trait') from what determines particular synaesthetic associations ('type').

  9. Limbic systems for emotion and for memory, but no single limbic system.

    PubMed

    Rolls, Edmund T

    2015-01-01

    The concept of a (single) limbic system is shown to be outmoded. Instead, anatomical, neurophysiological, functional neuroimaging, and neuropsychological evidence is described that anterior limbic and related structures including the orbitofrontal cortex and amygdala are involved in emotion, reward valuation, and reward-related decision-making (but not memory), with the value representations transmitted to the anterior cingulate cortex for action-outcome learning. In this 'emotion limbic system' a computational principle is that feedforward pattern association networks learn associations from visual, olfactory and auditory stimuli, to primary reinforcers such as taste, touch, and pain. In primates including humans this learning can be very rapid and rule-based, with the orbitofrontal cortex overshadowing the amygdala in this learning important for social and emotional behaviour. Complementary evidence is described showing that the hippocampus and limbic structures to which it is connected including the posterior cingulate cortex and the fornix-mammillary body-anterior thalamus-posterior cingulate circuit are involved in episodic or event memory, but not emotion. This 'hippocampal system' receives information from neocortical areas about spatial location, and objects, and can rapidly associate this information together by the different computational principle of autoassociation in the CA3 region of the hippocampus involving feedback. The system can later recall the whole of this information in the CA3 region from any component, a feedback process, and can recall the information back to neocortical areas, again a feedback (to neocortex) recall process. Emotion can enter this memory system from the orbitofrontal cortex etc., and be recalled back to the orbitofrontal cortex etc. during memory recall, but the emotional and hippocampal networks or 'limbic systems' operate by different computational principles, and operate independently of each other except insofar as an

  10. Cue-induced reinstatement of alcohol-seeking behavior is associated with increased ERK1/2 phosphorylation in specific limbic brain regions: blockade by the mGluR5 antagonist MPEP.

    PubMed

    Schroeder, Jason P; Spanos, Marina; Stevenson, Jennie R; Besheer, Joyce; Salling, Michael; Hodge, Clyde W

    2008-09-01

    Relapse to alcohol use after periods of abstinence is a hallmark behavioral pathology of alcoholism and a major clinical problem. Emerging evidence indicates that metabotropic glutamate receptor 5 (mGluR5) antagonists attenuate relapse to alcohol-seeking behavior but the molecular mechanisms of this potential therapeutic effect remain unexplored. The extracellular signal-regulated kinase (ERK1/2) pathway is downstream of mGluR5 and has been implicated in addiction. We sought to determine if cue-induced reinstatement of alcohol-seeking behavior, and its reduction by an mGluR5 antagonist, is associated with changes in ERK1/2 activation in reward-related limbic brain regions. Selectively-bred alcohol-preferring (P) rats were trained to lever press on a concurrent schedule of alcohol (15% v/v) vs. water reinforcement. Following 9 days of extinction, rats were given an additional extinction trial or injected with the mGluR5 antagonist MPEP (0, 1, 3, or 10mg/kg) and tested for cue-induced reinstatement. Brains were removed 90-min later from the rats in the extinction and MPEP (0 or 10mg/kg) conditions for analysis of p-ERK1/2, total ERK1/2, and p-ERK5 immunoreactivity (IR). Cue-induced reinstatement of alcohol-seeking behavior was associated with a three to five-fold increase in p-ERK1/2 IR in the basolateral amygdala and nucleus accumbens shell. MPEP administration blocked both the relapse-like behavior and increase in p-ERK1/2 IR. p-ERK1/2 IR in the central amygdala and NAcb core was dissociated with the relapse-like behavior and the pharmacological effect of mGluR5 blockade. No changes in total ERK or p-ERK5 were observed. These results suggest that exposure to cues previously associated with alcohol self-administration is sufficient to produce concomitant increases in relapse-like behavior and ERK1/2 activation in specific limbic brain regions. Pharmacological compounds, such as mGluR5 antagonists, that reduce cue-induced ERK1/2 activation may be useful for treatment

  11. 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.

  12. Electroencephalography of autoimmune limbic encephalopathy.

    PubMed

    Kaplan, Peter W; Sutter, Raoul

    2013-10-01

    There is an increasing recognition of autoimmune limbic encephalopathy with the hope for earlier diagnosis and expedited and improved treatment. Although antibody testing remains the definitive clinical diagnostic feature, the presentation of a rapid dementia, behavioral changes, and seizures leads to investigation using cerebral imaging, electroencephalography, and cerebrospinal fluid to confirm the diagnosis and also to exclude similar disorders. The electroencephalographer may be asked to comment on the types of electroencephalography abnormality and provide input toward the diagnosis of limbic encephalopathy. This article reviews the literature on limbic paraneoplastic and nonparaneoplastic encephalopathies, providing descriptions and examples of the electroencephalography findings. Typically, there are patterns of slow theta and delta activity and different patterns of temporal and frontal epileptic activity.

  13. Expression variations of chromogranin A and α1,2,4 GABA(A)Rs in discrete limbic and brainstem areas rescue cardiovascular alterations.

    PubMed

    Avolio, Ennio; Facciolo, Rosa Maria; Alò, Raffaella; Mele, Maria; Carelli, Antonio; Canonaco, Alessia; Mosciaro, Lucia; Talani, Giuseppe; Biggio, Giovanni; Sanna, Enrico; Mahata, Sushil K; Canonaco, Marcello

    2013-01-01

    Recent interferences of hemodynamic functions via modified brain neuronal mechanisms have proven to be major causes of dementia and sleeping disorders. In this work, cerebral expression differences of the neuroactive vesicular chromogranin A (CgA) and distinct α GABA(A)R subunits were detected in the facultative hibernating hamster. In particular, damaged neuronal fields of hypotensive torpor (TORP) state were correlated to elevated CgA and GABA(A)R α1, α4 mRNA levels in the paraventricular hypothalamic nucleus (PVN), central amygdalar nucleus (CeA) plus solitary tractus nucleus (NTS). Conversely, few neurodegeneration signals of hypertensive arousal (AROU) state, accounted for mostly lower CgA levels in the same areas. This state also provided increased α2-containing sites in amygdala, hippocampal and NTS neurons together with elevated α4-containing receptors in the periventricular hypothalamic nucleus (Pe). Interestingly in our hibernating model, CgA appeared to preferentially feature inhibitory neurosignals as indicated by preliminary perfusion of amygdalar sites with its highly specific antihypertensive derived peptide (catestatin) promoting GABA-dependent sIPSCs. Overall, evident neuronal damages plus altered expression capacities of CgA and α1-, α2-, α4-GABA(A)Rs in CeA, Pe, PVN as well as NTS during both hibernating states corroborate for the first time key molecular switching events guaranteeing useful cardiovascular rescuing abilities of neurodegenerative disorders.

  14. Cortico-limbic circuitry and the airways: Insights from functional neuroimaging of respiratory afferents and efferents

    PubMed Central

    Evans, Karleyton C.

    2010-01-01

    After nearly two decades of active research, functional neuroimaging has demonstrated utility in the identification of cortical, limbic, and paralimbic (cortico-limbic) brain regions involved in respiratory control and respiratory perception. Before the recent boon of human neuroimaging studies, the location of the principal components of respiratory-related cortico-limbic circuitry had been unknown and their function had been poorly understood. Emerging neuroimaging evidence in both healthy and patient populations suggests that cognitive and emotional/affective processing within cortico-limbic circuitry modulates respiratory control and respiratory perception. This paper will review functional neuroimaging studies of respiration with a focus on whole brain investigations of sensorimotor pathways that have identified respiratory-related neural circuitry known to overlap emotional/affective cortico-limbic circuitry. To aid the interpretation of present and future findings, the complexities and challenges underlying neuroimaging methodologies will also be reviewed as applied to the study of respiration physiology. PMID:20211221

  15. Blockade of 5-Ht3 receptors in the septal area increases Fos expression in selected brain areas.

    PubMed

    Urzedo-Rodrigues, Lilia S; Ferreira, Hilda S; Santana, Rejane Conceição; Luz, Carla Patrícia; Perrone, Camila F; Fregoneze, Josmara B

    2014-04-01

    Serotonin is widely distributed throughout the brain and is involved in a multiplicity of visceral, cognitive and behavioral responses. It has been previously shown that injections of different doses of ondansetron, a 5-HT3 receptor antagonist, into the medial septum/vertical limb of the diagonal band complex (MS/vDB) induce a hypertensive response in rats. On the other hand, administration of m-CPBG, a 5-HT3 agonist, into the MS/vDB inhibits the increase of blood pressure during restraint stress. However, it is unclear which neuronal circuitry is involved in these responses. The present study investigated Fos immunoreactive nuclei (Fos-IR) in different brain areas following the blockade of 5-HT3 receptors located in the MS/vDB in sham and in sinoaortic denervated (SAD) rats. Ondansetron injection into the MS/vDB increases Fos-IR in different brain areas including the limbic system (central amygdala and ventral part of the bed nucleus of the stria terminalis), hypothalamus (medial parvocellular parts of the paraventricular nucleus, anterodorsal preoptic area, dorsomedial hypothalamic nucleus), mesencephalon (ventrolateral periaqueductal gray region) and rhombencephalon (lateral parabrachial nucleus) in sham rats. Barodenervation results in higher Fos expression at the parvocellular and magnocellular part of the paraventricular nucleus, the lateral parabrachial nucleus, the central nucleus of amygdala, the locus coeruleus, the medial part of the nucleus of the solitary tract, the rostral ventrolateral medulla and the caudal ventrolateral medulla following 5-HT3receptor blockade in the MS/vDB. Based on the present results and previous data showing a hypertensive response to ondansetron injected into the MS/vDB, it is reasonable to suggest that 5-HT3receptors in the MS/vDB exert an inhibitory drive that may oscillate as a functional regulatory part of the complex central neuronal network participating in the control of blood pressure.

  16. 5-Hydroxytryptamine2C receptor contribution to m-chlorophenylpiperazine and N-methyl-beta-carboline-3-carboxamide-induced anxiety-like behavior and limbic brain activation.

    PubMed

    Hackler, Elizabeth A; Turner, Greg H; Gresch, Paul J; Sengupta, Saikat; Deutch, Ariel Y; Avison, Malcolm J; Gore, John C; Sanders-Bush, Elaine

    2007-03-01

    Activation of 5-hydroxytryptamine2C (5-HT(2C)) receptors by the 5-HT(2) receptor agonist m-chlorophenylpiperazine (m-CPP) elicits anxiety in humans and anxiety-like behavior in animals. We compared the effects of m-CPP with the anxiogenic GABA(A) receptor inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142) on both anxiety-like behavior and regional brain activation using functional magnetic resonance imaging (fMRI) in the rat. We also determined whether the selective 5-HT(2C) receptor antagonist SB 242084 [6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride] would blunt m-CPP or FG-7142-induced neuronal activation. Both m-CPP (3 mg/kg i.p.) and FG-7142 (10 mg/kg i.p.) elicited anxiety-like behavior when measured in the social interaction test, and pretreatment with SB 242084 (1 mg/kg i.p.) completely blocked the behavioral effects of both anxiogenic drugs. Regional brain activation in vivo in response to anxiogenic drug challenge was determined by blood oxygen level-dependent (BOLD) fMRI using a powerful 9.4T magnet. Region of interest analyses revealed that m-CPP and FG-7142 significantly increased BOLD signals in brain regions that have been linked to anxiety, including the amygdala, dorsal hippocampus, and medial hypothalamus. These BOLD signal increases were blocked by pretreatment with SB 242084. In contrast, injection of m-CPP and FG-7142 resulted in BOLD signal decreases in the medial prefrontal cortex that were not blocked by SB 242084. In conclusion, the brain activation signals produced by anxiogenic doses of both m-CPP and FG-7142 are mediated at least partially by the 5-HT(2C) receptor, indicating that this receptor is a key component in anxiogenic neural circuitry.

  17. 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

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

    PubMed

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

    2014-11-01

    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.

  19. First episode drug-naïve major depressive disorder with panic disorder: gray matter deficits in limbic and default network structures.

    PubMed

    Lai, Chien-Han; Hsu, Yuan-Yu; Wu, Yu-Te

    2010-10-01

    This study was designed to investigate the structural differences in the brains of first episode, drug-naïve patients with major depressive disorder and panic disorder versus healthy control subjects. High-resolution brain magnetic resonance images were performed on patients and health control subjects (age, sex and handedness matched). Structural magnetic resonance images of brain were estimated by optimized voxel-based morphometry of FSL (FMRIB Software Library). Patients had deficits of gray matter volumes over right anterior cingulate cortex, right medial frontal gyrus, left posterior cingulate cortex, right parahippocampal gyrus, limbic areas, occipital lingual gyrus and bilateral cerebellums when compared to controls. These results suggested that this group of patients has possible deficits of gray matter volumes over the default-mode network, fronto-cingulate and limbic structures. The decline of gray matter volumes might have started since the first episode. Copyright 2010 Elsevier B.V. and ECNP. All rights reserved.

  20. Lesion Analysis of the Brain Areas Involved in Language Comprehension

    ERIC Educational Resources Information Center

    Dronkers, Nina F.; Wilkins, David P.; Van Valin, Robert D., Jr.; Redfern, Brenda B.; Jaeger, Jeri J.

    2004-01-01

    The cortical regions of the brain traditionally associated with the comprehension of language are Wernicke's area and Broca's area. However, recent evidence suggests that other brain regions might also be involved in this complex process. This paper describes the opportunity to evaluate a large number of brain-injured patients to determine which…

  1. Lesion Analysis of the Brain Areas Involved in Language Comprehension

    ERIC Educational Resources Information Center

    Dronkers, Nina F.; Wilkins, David P.; Van Valin, Robert D., Jr.; Redfern, Brenda B.; Jaeger, Jeri J.

    2004-01-01

    The cortical regions of the brain traditionally associated with the comprehension of language are Wernicke's area and Broca's area. However, recent evidence suggests that other brain regions might also be involved in this complex process. This paper describes the opportunity to evaluate a large number of brain-injured patients to determine which…

  2. Limbic grey matter changes in early Parkinson's disease.

    PubMed

    Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

    2017-05-02

    The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The

  3. In vivo magnetic resonance imaging of the human limbic white matter

    PubMed Central

    Mori, Susumu; Aggarwal, Manisha

    2014-01-01

    The limbic system mediates memory, behavior, and emotional output in the human brain, and is implicated in the pathology of Alzheimer’s disease and a wide spectrum of related neurological disorders. In vivo magnetic resonance imaging (MRI) of structural components comprising the limbic system and their interconnections via white matter pathways in the human brain has helped define current understanding of the limbic model based on the classical circuit proposed by Papez. MRI techniques, including diffusion MR imaging, provide a non-invasive method to characterize white matter tracts of the limbic system, and investigate pathological changes that affect these pathways in clinical settings. This review focuses on delineation of the anatomy of major limbic tracts in the human brain, namely, the cingulum, the fornix and fimbria, and the stria terminalis, based on in vivo MRI contrasts. The detailed morphology and intricate trajectories of these pathways that can be identified using relaxometry-based and diffusion-weighted MRI provide an important anatomical reference for evaluation of clinical disorders commonly associated with limbic pathology. PMID:25505883

  4. Reduced limbic metabolism and fronto-cortical volume in rats vulnerable to alcohol addiction

    PubMed Central

    Gozzi, Alessandro; Agosta, Federica; Massi, Maurizio; Ciccocioppo, Roberto; Bifone, Angelo

    2014-01-01

    Alcohol abuse is associated with long-term reductions in fronto-cortical volume and limbic metabolism. However, an unanswered question in alcohol research is whether these alterations are the sole consequence of chronic alcohol use, or contain heritable contributions reflecting biological propensity toward ethanol addiction. Animal models of genetic predisposition to alcohol dependence can be used to investigate the role of inborn brain abnormalities in the aetiology of alcoholism. Here we used magnetic resonance imaging (MRI) in e Marchigian Sardinian (msP) alcohol-preferring rats to assess the presence of inherited structural or functional brain alterations. Alcohol-naïve msP (N=22) and control rats (N=26) were subjected to basal cerebral blood volume (bCBV) mapping followed by voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics mapping of white matter fractional anisotropy. msP rats exhibited significantly reduced bCBV, an established marker of resting brain function, in focal cortico-limbic and thalamic areas, together with reduced gray matter volume in the thalamus, ventral tegmental area, insular and cingulate cortex. No statistically significant differences in fractional anisotropy were observed between groups. These findings highlight the presence of inborn gray matter and metabolic abnormalities in alcohol-naïve msP rats, the localization and sign of which are remarkably similar to those mapped in abstinent alcoholics and subjects at high risk for alcohol dependence. Collectively, these results point for a significant role of heritable neurofunctional brain alterations in biological propensity toward ethanol addiction, and support the translational use of advanced imaging methods to describe the circuital determinants of vulnerability to drug addiction. PMID:23261637

  5. Reduced limbic metabolism and fronto-cortical volume in rats vulnerable to alcohol addiction.

    PubMed

    Gozzi, Alessandro; Agosta, Federica; Massi, Maurizio; Ciccocioppo, Roberto; Bifone, Angelo

    2013-04-01

    Alcohol abuse is associated with long-term reductions in fronto-cortical volume and limbic metabolism. However, an unanswered question in alcohol research is whether these alterations are the sole consequence of chronic alcohol use, or contain heritable contributions reflecting biological propensity toward ethanol addiction. Animal models of genetic predisposition to alcohol dependence can be used to investigate the role of inborn brain abnormalities in the aetiology of alcoholism. Here we used magnetic resonance imaging (MRI) in the Marchigian-Sardinian (msP) alcohol-preferring rats to assess the presence of inherited structural or functional brain alterations. Alcohol-naïve msP (N=22) and control rats (N=26) were subjected to basal cerebral blood volume (bCBV) mapping followed by voxel-based morphometry (VBM) of grey matter and tract-based spatial statistics mapping of white matter fractional anisotropy. msP rats exhibited significantly reduced bCBV, an established marker of resting brain function, in focal cortico-limbic and thalamic areas, together with reduced grey matter volume in the thalamus, ventral tegmental area, insular and cingulate cortex. No statistically significant differences in fractional anisotropy were observed between groups. These findings highlight the presence of inborn grey matter and metabolic abnormalities in alcohol-naïve msP rats, the localization and sign of which are remarkably similar to those mapped in abstinent alcoholics and subjects at high risk for alcohol dependence. Collectively, these results point for a significant role of heritable neurofunctional brain alterations in biological propensity toward ethanol addiction, and support the translational use of advanced imaging methods to describe the circuital determinants of vulnerability to drug addiction. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Disgust and fear recognition in paraneoplastic limbic encephalitis.

    PubMed

    Sprengelmeyer, Reiner; Atkinson, Anthony P; Sprengelmeyer, Anke; Mair-Walther, Johanna; Jacobi, Christian; Wildemann, Brigitte; Dittrich, Winand H; Hacke, Werner

    2010-05-01

    Paraneoplastic limbic encephalitis (PNLE) affects limbic portions of the brain associated with recognition of social signals of emotions. Yet it is not known whether this perceptual ability is impaired in individuals with PNLE. We therefore conducted a single case study to explore possible impairments in recognising facially, vocally and bodily expressed emotions, using standardised emotion recognition tests. Facial expression recognition was tested with two forced-choice emotion-labelling tasks using static faces with either prototypical or morphed blends of basic emotions. Recognition of vocally and bodily expressed emotions was also tested with forced-choice labelling tasks, one based on prosodic cues, the other on whole-body movement cues. We found a deficit in fear and disgust recognition from both face and voice, while recognition of bodily expressed emotions was unaffected. These findings are consistent with data from previous studies demonstrating critical roles for certain brain regions - particularly the amygdala and insular cortex - in processing facially and vocally displayed basic emotions, and furthermore, suggest that recognition of bodily expressed emotions may not depend on neural structures involved in facial and vocal emotion recognition. Impaired facial and vocal emotion recognition may form a further neuropsychological marker of limbic encephalitis, in addition to the already well-described mnestic deficits.

  7. Cognitive and Emotional Modulation of Brain Default Operation

    ERIC Educational Resources Information Center

    Pallesen, Karen Johanne; Brattico, Elvira; Bailey, Christopher J.; Korvenoja, Antti; Gjedde, Albert

    2009-01-01

    Goal-directed behavior lowers activity in brain areas that include the medial frontal cortex, the medial and lateral parietal cortex, and limbic and paralimbic brain regions, commonly referred to as the "default network." These activity decreases are believed to reflect the interruption of processes that are ongoing when the mind is in a restful…

  8. Cognitive and Emotional Modulation of Brain Default Operation

    ERIC Educational Resources Information Center

    Pallesen, Karen Johanne; Brattico, Elvira; Bailey, Christopher J.; Korvenoja, Antti; Gjedde, Albert

    2009-01-01

    Goal-directed behavior lowers activity in brain areas that include the medial frontal cortex, the medial and lateral parietal cortex, and limbic and paralimbic brain regions, commonly referred to as the "default network." These activity decreases are believed to reflect the interruption of processes that are ongoing when the mind is in a restful…

  9. LIMBIC CIRCUITRY OF THE MIDLINE THALAMUS

    PubMed Central

    Vertes, Robert P.; Linley, Stephanie B.; Hoover, Walter B.

    2016-01-01

    The thalamus was subdivided into three major groups: sensorimotor nuclei (or principal/relay nuclei), limbic nuclei and nuclei bridging these two domains. Limbic nuclei of thalamus (or ‘limbic thalamus’) consist of the anterior nuclei, midline nuclei, medial division of the mediodorsal nucleus (MDm) and central medial nucleus (CM) of the intralaminar complex. The midline nuclei include the paraventricular (PV) and paratenial (PT) nuclei, dorsally, and the reuniens (RE) and rhomboid (RH) nuclei, ventrally. The ‘limbic’ thalamic nuclei predominantly connect with limbic-related structures and serve a direct role in limbic–associated functions. Regarding the midline nuclei, RE/RH mainly target limbic cortical structures, particularly the hippocampus and the medial prefrontal cortex. Accordingly, RE/RH participate in functions involving interactions of the HF and mPFC. By contrast, PV/PT mainly project to limbic subcortical structures, particularly the amygdala and nucleus accumbens, and hence are critically involved in affective behaviors such as stress/anxiety, feeding behavior, and drug seeking activities. The anatomical/functional characteristics of MDm and CM are very similar to those of the midline nuclei and hence the collection of nuclei extending dorsoventrally along the midline/paramidline of the thalamus constitute the core of the ‘limbic thalamus’. PMID:25616182

  10. Aberrant hippocampal neurogenesis after limbic kindling: Relationship to BDNF and hippocampal-dependent memory.

    PubMed

    Botterill, J J; Brymer, K J; Caruncho, H J; Kalynchuk, L E

    2015-06-01

    Seizures dramatically increase the number of adult generated neurons in the hippocampus. However, it is not known whether this effect depends on seizures that originate in specific brain regions or whether it is nonspecific to seizure activity regardless of origin. We used kindling of different brain sites to address this question. Rats received 99 kindling stimulations of the basolateral amygdala, dorsal hippocampus, or caudate nucleus over a 6-week period. After kindling, we counted the number of adult generated hippocampal neurons that were birth-dated with the proliferative marker bromodeoxyuridine (BrdU) to evaluate cell proliferation and survival under conditions of repeated seizures. Next, we counted the number of doublecortin immunoreactive (DCX-ir) cells and evaluated their dendritic complexity to determine if limbic and nonlimbic seizures have differential effects on neuronal maturation. We also quantified hippocampal brain-derived neurotrophin factor (BDNF) protein levels using an ELISA kit and assessed memory performance using a hippocampal-dependent fear conditioning paradigm. We found that limbic, but not nonlimbic, seizures dramatically increased hippocampal cell proliferation and the number of hilar-CA3 ectopic granule cells. Further, limbic kindling promoted dendritic outgrowth of DCX-ir cells and the number of DCX-ir cells containing basal dendrites. Limbic kindling also enhanced BDNF protein levels throughout the entire hippocampus and impaired the retrieval of fear memories. Collectively, our results suggest a relationship between limbic seizures, neurogenesis, BDNF protein, and cognition.

  11. Chronic myofascial temporomandibular pain is associated with neural abnormalities in the trigeminal and limbic systems

    PubMed Central

    Shen, Yoshi F.; Goddard, Greg; Mackey, Sean C.

    2010-01-01

    Myofascial pain of the temporomandibular region (M-TMD) is a common, but poorly understood chronic disorder. It is unknown whether the condition is a peripheral problem, or a disorder of the central nervous system (CNS). To investigate possible CNS substrates of M-TMD, we compared the brain morphology of 15 women with M-TMD to 15 age- and gender-matched healthy controls. High-resolution structural brain and brainstem scans were carried out using magnetic resonance imaging (MRI), and data were analyzed using a voxel-based morphometry approach. The M-TMD group evidenced decreased or increased gray matter volume compared to controls in several areas of the trigeminothalamocortical pathway, including brainstem trigeminal sensory nuclei, the thalamus, and the primary somatosensory cortex. In addition, M-TMD individuals showed increased gray matter volume compared to controls in limbic regions such as the posterior putamen, globus pallidus, and anterior insula. Within the M-TMD group, jaw pain, pain tolerance, and pain duration were differentially associated with brain and brainstem gray matter volume. Self-reported pain severity was associated with increased gray matter in the rostral anterior cingulate cortex and posterior cingulate. Sensitivity to pressure algometry was associated with decreased gray matter in the pons, corresponding to the trigeminal sensory nuclei. Longer pain duration was associated with greater gray matter in the posterior cingulate, hippocampus, midbrain, and cerebellum. The pattern of gray matter abnormality found in M-TMD individuals suggests the involvement of trigeminal and limbic system dysregulation, as well as potential somatotopic reorganization in the putamen, thalamus, and somatosensory cortex. PMID:20236763

  12. Common effects of fat, ethanol, and nicotine on enkephalin in discrete areas of the brain.

    PubMed

    Chang, G-Q; Karatayev, O; Barson, J R; Liang, S C; Leibowitz, S F

    2014-09-26

    Fat, ethanol, and nicotine share a number of properties, including their ability to reinforce behavior and produce overconsumption. To test whether these substances act similarly on the same neuronal populations in specific brain areas mediating these behaviors, we administered the substances short-term, using the same methods and within the same experiment, and measured their effects, in areas of the hypothalamus (HYPO), amygdala (AMYG), and nucleus accumbens (NAc), on mRNA levels of the opioid peptide, enkephalin (ENK), using in situ hybridization and on c-Fos immunoreactivity (ir) to indicate neuronal activity, using immunofluorescence histochemistry. In addition, we examined for comparison another reinforcing substance, sucrose, and also took measurements of stress-related behaviors and circulating corticosterone (CORT) and triglycerides (TG), to determine if they contribute to these substances' behavioral and physiological effects. Adult Sprague-Dawley rats were gavaged three times daily over 5 days with 3.5 mL of water, Intralipid (20% v/v), ethanol (12% v/v), nicotine (0.01% w/v) or sucrose (22% w/v) (approximately 7 kcal/dose), and tail vein blood was collected for measurements of circulating CORT and TG. On day five, animals were sacrificed, brains removed, and the HYPO, AMYG, and NAc processed for single- or double-labeling of ENK mRNA and c-Fos-ir. Fat, ethanol, and nicotine, but not sucrose, increased the single- and double-labeling of ENK and c-Fos-ir in precisely the same brain areas, the middle parvocellular but not lateral area of the paraventricular nucleus, central but not basolateral nucleus of the AMYG, and core but not shell of the NAc. While having little effect on stress-related behaviors or CORT levels, fat, ethanol, and nicotine all increased circulating levels of TG. These findings suggest that the overconsumption of these three substances and their potential for abuse are mediated by the same populations of ENK-expressing neurons in

  13. Cortical deactivation induced by subcortical network dysfunction in limbic seizures

    PubMed Central

    Englot, Dario J.; Modi, Badri; Mishra, Asht M.; DeSalvo, Matthew; Hyder, Fahmeed; Blumenfeld, Hal

    2009-01-01

    Normal human consciousness may be impaired by two possible routes: direct reduced function in widespread cortical regions, or indirect disruption of subcortical activating systems. The route through which temporal lobe limbic seizures impair consciousness is not known. We recently developed an animal model which, like human limbic seizures, exhibits neocortical deactivation including cortical slow waves and reduced cortical cerebral blood flow (CBF). We now find through functional MRI (fMRI) that electrically-stimulated hippocampal seizures in rats cause increased activity in subcortical structures including the septal area and mediodorsal thalamus, along with reduced activity in frontal, cingulate, and retrosplenial cortex. Direct recordings from the hippocampus, septum, and medial thalamus demonstrated fast poly-spike activity associated with increased neuronal firing and CBF, while frontal cortex showed slow oscillations with decreased neuronal firing and CBF. Stimulation of septal area, but not hippocampus or medial thalamus, in the absence of a seizure resulted in cortical deactivation with slow oscillations and behavioral arrest, resembling changes seen during limbic seizures. Transecting the fornix, the major route from hippocampus to subcortical structures, abolished the negative cortical and behavioral effects of seizures. Cortical slow oscillations and behavioral arrest could be reconstituted in fornix-lesioned animals by inducing synchronous activity in the hippocampus and septal area, implying involvement of a downstream region converged upon by both structures. These findings suggest that limbic seizures may cause neocortical deactivation indirectly, through impaired subcortical function. If confirmed, subcortical networks may represent a target for therapies aimed at preserving consciousness in human temporal lobe seizures. PMID:19828814

  14. [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.

  15. Compulsive sexual behavior: Prefrontal and limbic volume and interactions

    PubMed Central

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

    2016-01-01

    Abstract Background 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). Methods 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). Results 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. Conclusions 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. PMID:27787929

  16. Intrinsic Limbic and Paralimbic Networks Are Associated With Criminal Psychopathy

    PubMed Central

    Juárez, Michelle; Kiehl, Kent A.; Calhoun, Vince D.

    2014-01-01

    Background Psychopathy is a personality disorder associated with impairments in decision-making, empathy, and impulsivity. Recent brain imaging studies suggest that psychopathy is associated with abnormalities in limbic/paralimbic brain regions. To date, no studies have examined functional brain connectivity measures using independent component analyses (ICA) in adults with psychopathy. Here, we test hypotheses regarding paralimbic connectivity in adult incarcerated individuals stratified by psychopathy scores. Methods One hundred and two prison inmates were rated using the Hare Psychopathy Checklist-Revised (PCL-R). FMRI data were collected while subjects performed an auditory target detection “oddball” task. FMRI data were analyzed using group ICA to identify functional networks responding to the oddball task correlating with psychopathy scores. Results Components demonstrating significant correlations with psychopathy included a default mode network, a frontoparietal component, and a visual/posterior cingulate component. Modulation trends correlated strongly with factor 2 (impulsivity) and total PCL-R scores in the frontoparietal and visual/posterior cingulate networks, and with factor 1 (affective) scores within the default mode network. The posterior cingulate region factored significantly in the modulation trends observed. Conclusion Consistent with the hypothesis of limbic/paralimbic abnormalities associated with psychopathy, modulation trends correlated strongly with PCL-R scores. There is strong evidence to implicate the posterior cingulate in aberrant functional connectivity associated with the manifestation of psychopathic symptoms. Future investigations comparing functional trends associated with the posterior cingulate in psychopathic subjects may provide further insight into the manifestation of this disorder. PMID:22431294

  17. Broca's Area: A Problem in Language-Brain Relationships

    ERIC Educational Resources Information Center

    Whitaker, H. A.; Selnes, O. A.

    1975-01-01

    How significantly is Broca's Area related to speech? It is considered here to be definitely a component in the language mechanism of the brain. It is also stated that this area is unique to people and that it has no unitary function, yet it is specialized for certain expressive (motor) functions. (SCC)

  18. Characterizing the Input-Output Function of the Olfactory-Limbic Pathway in the Guinea Pig.

    PubMed

    Breschi, Gian Luca; Ciliberto, Carlo; Nieus, Thierry; Rosasco, Lorenzo; Taverna, Stefano; Chiappalone, Michela; Pasquale, Valentina

    2015-01-01

    Nowadays the neuroscientific community is taking more and more advantage of the continuous interaction between engineers and computational neuroscientists in order to develop neuroprostheses aimed at replacing damaged brain areas with artificial devices. To this end, a technological effort is required to develop neural network models which can be fed with the recorded electrophysiological patterns to yield the correct brain stimulation to recover the desired functions. In this paper we present a machine learning approach to derive the input-output function of the olfactory-limbic pathway in the in vitro whole brain of guinea pig, less complex and more controllable than an in vivo system. We first experimentally characterized the neuronal pathway by delivering different sets of electrical stimuli from the lateral olfactory tract (LOT) and by recording the corresponding responses in the lateral entorhinal cortex (l-ERC). As a second step, we used information theory to evaluate how much information output features carry about the input. Finally we used the acquired data to learn the LOT-l-ERC "I/O function," by means of the kernel regularized least squares method, able to predict l-ERC responses on the basis of LOT stimulation features. Our modeling approach can be further exploited for brain prostheses applications.

  19. Repeated interactions with females elevate metabolic capacity in the limbic system of male rats.

    PubMed

    Sakata, Jon T; Gonzalez-Lima, F; Gupta, Ajay; Crews, David

    2002-05-17

    The effect of heterosexual social experience on brain metabolic capacity was investigated by measuring the activity of cytochrome oxidase, a rate-limiting enzyme in oxidative metabolism. Male Sprague-Dawley rats were kept naïve or allowed to copulate with receptive females three (3 F males) or 16 times (16 F males). Throughout the vomeronasal system and other limbic areas, 16 F males had elevated metabolic capacity relative to naïve and 3 F males, whereas no significant differences in brain metabolism were found between 3 F and naïve males. Behavioral differences were also found between 3 F and 16 F males. In a second experiment, we assessed differences in brain metabolism between sexually active and inactive males given only one opportunity to copulate and found no significant difference in neural metabolism between these males. This suggests that the differences found in the first experiment were primarily driven by differences in repeated experience rather than by sexual performance between 16 F and 3 F males. We speculate that these changes in brain metabolic capacity could be related to immediate early gene expression during copulation and could underlie the long-term behavioral changes accompanying heterosexual social experience.

  20. Affective brain areas and sleep disordered breathing

    PubMed Central

    Harper, Ronald M.; Kumar, Rajesh; Macey, Paul M.; Woo, Mary A.; Ogren, Jennifer A.

    2014-01-01

    The neural damage accompanying the hypoxia, reduced perfusion, and other consequences of sleep-disordered breathing found in obstructive sleep apnea, heart failure (HF), and congenital central hypoventilation syndrome (CCHS), appears in areas that serve multiple functions, including emotional drives to breathe, and involve systems that serve affective, cardiovascular, and breathing roles. The damage, assessed with structural magnetic resonance imaging (MRI) procedures, shows tissue loss or water content and diffusion changes indicative of injury, and impaired axonal integrity between structures; damage is preferentially unilateral. Functional MRI responses in affected areas also are time- or amplitude- distorted to ventilatory or autonomic challenges. Among the structures injured are the insular, cingulate, and ventral medial prefrontal cortices, as well as cerebellar deep nuclei and cortex, anterior hypothalamus, raphé, ventrolateral medulla, basal ganglia and, in CCHS, the locus coeruleus. Raphé and locus coeruleus injury may modify serotonergic and adrenergic modulation of upper airway and arousal characteristics. Since both axons and gray matter show injury, the consequences to function, especially to autonomic, cognitive, and mood regulation, are major. Several affected rostral sites, including the insular and cingulate cortices and hippocampus, mediate aspects of dyspnea, especially in CCHS, while others, including the anterior cingulate and thalamus, participate in initiation of inspiration after central breathing pauses, and the medullary injury can impair baroreflex and breathing control. The ancillary injury associated with sleep-disordered breathing to central structures can elicit multiple other distortions in cardiovascular, cognitive, and emotional functions in addition to effects on breathing regulation. PMID:24746053

  1. Early neuronal responses in right limbic structures mediate harmony incongruity processing in musical experts.

    PubMed

    James, Clara E; Britz, Juliane; Vuilleumier, Patrik; Hauert, Claude-Alain; Michel, Christoph M

    2008-10-01

    In western tonal music, musical phrases end with an explicit harmonic consequent which is highly expected. As such expectation is a consequence of musical background, cerebral processing of incongruities of musical grammar might be a function of expertise. We hypothesized that a subtle incongruity of standard closure should evoke a profound and rapid reaction in an expert's brain. If such a reaction is due to neuroplasticity as a consequence of musical training, it should be correlated with distinctive activations in sensory, motor and/or cognitive function related brain areas in response to the incongruent closure. Using event related potential (ERP) source imaging, we determined the temporal dynamics of neuronal activity in highly trained pianists and musical laymen in response to syntactic harmonic incongruities in expressive music, which were easily detected by the experts but not by the laymen. Our results revealed that closure incongruity evokes a selective early response in musical experts, characterized by a strong, right lateralized negative ERP component. Statistical source analysis could demonstrate putative contribution to the generation of this component in right temporal-limbic areas, encompassing hippocampal complex and amygdala, and in right insula. Its early onset (approximately 200 ms) preceded responses in frontal areas that may reflect more conscious processing. These results go beyond previous work demonstrating that musical training can change activity of sensory and motor areas during musical or audio-motor tasks, and suggest that functional plasticity in right medial-temporal structures and insula also modulates processing of subtle harmonic incongruities.

  2. A brain area for visual numerals.

    PubMed

    Shum, Jennifer; Hermes, Dora; Foster, Brett L; Dastjerdi, Mohammad; Rangarajan, Vinitha; Winawer, Jonathan; Miller, Kai J; Parvizi, Josef

    2013-04-17

    Is there a distinct area within the human visual system that has a preferential response to numerals, as there is for faces, words, or scenes? We addressed this question using intracranial electrophysiological recordings and observed a significantly higher response in the high-frequency broadband range (high γ, 65-150 Hz) to visually presented numerals, compared with morphologically similar (i.e., letters and false fonts) or semantically and phonologically similar stimuli (i.e., number words and non-number words). Anatomically, this preferential response was consistently localized in the inferior temporal gyrus and anterior to the temporo-occipital incisure. This region lies within or close to the fMRI signal-dropout zone produced by the nearby auditory canal and venous sinus artifacts, an observation that may account for negative findings in previous fMRI studies of preferential response to numerals. Because visual numerals are culturally dependent symbols that are only learned through education, our novel finding of anatomically localized preferential response to such symbols provides a new example of acquired category-specific responses in the human visual system.

  3. Isolation of speech area from focal brain ischemia.

    PubMed

    Bogousslavsky, J; Regli, F; Assal, G

    1985-01-01

    A patient with atrial fibrillation and internal carotid artery occlusion developed mixed transcortical aphasia. The CT scan showed two recent distinct infarcts in the dominant hemisphere, one in the precentral artery area (pial artery infarct) and one in the borderzone area between the posterior and middle cerebral arteries territories (watershed infarct). The perisylvian speech areas were spared, but probably disconnected from other areas by the infarcts. The syndrome of isolation of speech area may be caused by vascular conditions which are able to produce simultaneous pial artery and watershed infarcts, and is not necessarily related to more extensive processes of the brain.

  4. Impact of Size and Delay on Neural Activity in the Rat Limbic Corticostriatal System

    PubMed Central

    Roesch, Matthew R.; Bryden, Daniel W.

    2011-01-01

    A number of factors influence an animal’s economic decisions. Two most commonly studied are the magnitude of and delay to reward. To investigate how these factors are represented in the firing rates of single neurons, we devised a behavioral task that independently manipulated the expected delay to and size of reward. Rats perceived the differently delayed and sized rewards as having different values and were more motivated under short delay and big-reward conditions than under long delay and small reward conditions as measured by percent choice, accuracy, and reaction time. Since the creation of this task, we have recorded from several different brain areas including, orbitofrontal cortex, striatum, amygdala, substantia nigra pars reticulata, and midbrain dopamine neurons. Here, we review and compare those data with a substantial focus on those areas that have been shown to be critical for performance on classic time discounting procedures and provide a potential mechanism by which they might interact when animals are deciding between differently delayed rewards. We found that most brain areas in the cortico-limbic circuit encode both the magnitude and delay to reward delivery in one form or another, but only a few encode them together at the single neuron level. PMID:22363252

  5. Impact of size and delay on neural activity in the rat limbic corticostriatal system.

    PubMed

    Roesch, Matthew R; Bryden, Daniel W

    2011-01-01

    A number of factors influence an animal's economic decisions. Two most commonly studied are the magnitude of and delay to reward. To investigate how these factors are represented in the firing rates of single neurons, we devised a behavioral task that independently manipulated the expected delay to and size of reward. Rats perceived the differently delayed and sized rewards as having different values and were more motivated under short delay and big-reward conditions than under long delay and small reward conditions as measured by percent choice, accuracy, and reaction time. Since the creation of this task, we have recorded from several different brain areas including, orbitofrontal cortex, striatum, amygdala, substantia nigra pars reticulata, and midbrain dopamine neurons. Here, we review and compare those data with a substantial focus on those areas that have been shown to be critical for performance on classic time discounting procedures and provide a potential mechanism by which they might interact when animals are deciding between differently delayed rewards. We found that most brain areas in the cortico-limbic circuit encode both the magnitude and delay to reward delivery in one form or another, but only a few encode them together at the single neuron level.

  6. [Deep brain stimulation. New target areas and new indications].

    PubMed

    Reich, M M; Kühn, A A; Volkmann, J

    2013-08-01

    Many patients with neurological movement disorders and psychiatric diseases cannot yet be adequately treated with conventional methods. Deep brain stimulation represents an important extension of therapeutic options by which invasive electrodes are implanted in various subcortical brain areas in order to achieve an improvement in motor and psychiatric symptoms by high frequency stimulation. Up to 2012 approximately 100,000 patients had been treated with deep brain stimulation worldwide. The indications for deep brain stimulation were essentially already established indications, such as idiopathic Parkinson's syndrome, dystonia and tremors. The newer indications which include in particular psychiatric symptoms, such as depression, obsessive diseases, addiction and Tourette syndrome, are as yet limited to approximately 5 % of treated patients. An increasingly better understanding of the system physiology of neurological and psychiatric diseases has promoted the search for new target areas and indications for treatment by neuromodulation. This article gives an overview of the latest developments in the established and also the developing application areas of deep brain stimulation.

  7. Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function

    PubMed Central

    Jiang, Heidi; Zhou, Guangyu; Arora, Nikita; Schuele, Stephan; Rosenow, Joshua; Gottfried, Jay A.

    2016-01-01

    The need to breathe links the mammalian olfactory system inextricably to the respiratory rhythms that draw air through the nose. In rodents and other small animals, slow oscillations of local field potential activity are driven at the rate of breathing (∼2–12 Hz) in olfactory bulb and cortex, and faster oscillatory bursts are coupled to specific phases of the respiratory cycle. These dynamic rhythms are thought to regulate cortical excitability and coordinate network interactions, helping to shape olfactory coding, memory, and behavior. However, while respiratory oscillations are a ubiquitous hallmark of olfactory system function in animals, direct evidence for such patterns is lacking in humans. In this study, we acquired intracranial EEG data from rare patients (Ps) with medically refractory epilepsy, enabling us to test the hypothesis that cortical oscillatory activity would be entrained to the human respiratory cycle, albeit at the much slower rhythm of ∼0.16–0.33 Hz. Our results reveal that natural breathing synchronizes electrical activity in human piriform (olfactory) cortex, as well as in limbic-related brain areas, including amygdala and hippocampus. Notably, oscillatory power peaked during inspiration and dissipated when breathing was diverted from nose to mouth. Parallel behavioral experiments showed that breathing phase enhances fear discrimination and memory retrieval. Our findings provide a unique framework for understanding the pivotal role of nasal breathing in coordinating neuronal oscillations to support stimulus processing and behavior. SIGNIFICANCE STATEMENT Animal studies have long shown that olfactory oscillatory activity emerges in line with the natural rhythm of breathing, even in the absence of an odor stimulus. Whether the breathing cycle induces cortical oscillations in the human brain is poorly understood. In this study, we collected intracranial EEG data from rare patients with medically intractable epilepsy, and found evidence

  8. Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function.

    PubMed

    Zelano, Christina; Jiang, Heidi; Zhou, Guangyu; Arora, Nikita; Schuele, Stephan; Rosenow, Joshua; Gottfried, Jay A

    2016-12-07

    The need to breathe links the mammalian olfactory system inextricably to the respiratory rhythms that draw air through the nose. In rodents and other small animals, slow oscillations of local field potential activity are driven at the rate of breathing (∼2-12 Hz) in olfactory bulb and cortex, and faster oscillatory bursts are coupled to specific phases of the respiratory cycle. These dynamic rhythms are thought to regulate cortical excitability and coordinate network interactions, helping to shape olfactory coding, memory, and behavior. However, while respiratory oscillations are a ubiquitous hallmark of olfactory system function in animals, direct evidence for such patterns is lacking in humans. In this study, we acquired intracranial EEG data from rare patients (Ps) with medically refractory epilepsy, enabling us to test the hypothesis that cortical oscillatory activity would be entrained to the human respiratory cycle, albeit at the much slower rhythm of ∼0.16-0.33 Hz. Our results reveal that natural breathing synchronizes electrical activity in human piriform (olfactory) cortex, as well as in limbic-related brain areas, including amygdala and hippocampus. Notably, oscillatory power peaked during inspiration and dissipated when breathing was diverted from nose to mouth. Parallel behavioral experiments showed that breathing phase enhances fear discrimination and memory retrieval. Our findings provide a unique framework for understanding the pivotal role of nasal breathing in coordinating neuronal oscillations to support stimulus processing and behavior. Animal studies have long shown that olfactory oscillatory activity emerges in line with the natural rhythm of breathing, even in the absence of an odor stimulus. Whether the breathing cycle induces cortical oscillations in the human brain is poorly understood. In this study, we collected intracranial EEG data from rare patients with medically intractable epilepsy, and found evidence for respiratory entrainment

  9. 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.

  10. Evidence for evolutionary specialization in human limbic structures

    PubMed Central

    Barger, Nicole; Hanson, Kari L.; Teffer, Kate; Schenker-Ahmed, Natalie M.; Semendeferi, Katerina

    2014-01-01

    Increasingly, functional and evolutionary research has highlighted the important contribution emotion processing makes to complex human social cognition. As such, it may be asked whether neural structures involved in emotion processing, commonly referred to as limbic structures, have been impacted in human brain evolution. To address this question, we performed an extensive evolutionary analysis of multiple limbic structures using modern phylogenetic tools. For this analysis, we combined new volumetric data for the hominoid (human and ape) amygdala and 4 amygdaloid nuclei, hippocampus, and striatum, collected using stereological methods in complete histological series, with previously published datasets on the amygdala, orbital and medial frontal cortex, and insula, as well as a non-limbic structure, the dorsal frontal cortex, for contrast. We performed a parallel analysis using large published datasets including many anthropoid species (human, ape, and monkey), but fewer hominoids, for the amygdala and 2 amygdaloid subdivisions, hippocampus, schizocortex, striatum, and septal nuclei. To address evolutionary change, we compared observed human values to values predicted from regressions run through (a) non-human hominoids and (b) non-human anthropoids, assessing phylogenetic influence using phylogenetic generalized least squares regression. Compared with other hominoids, the volumes of the hippocampus, the lateral nucleus of the amygdala, and the orbital frontal cortex were, respectively, 50, 37, and 11% greater in humans than predicted for an ape of human hemisphere volume, while the medial and dorsal frontal cortex were, respectively, 26 and 29% significantly smaller. Compared with other anthropoids, only human values for the striatum fell significantly below predicted values. Overall, the data present support for the idea that regions involved in emotion processing are not necessarily conserved or regressive, but may even be enhanced in recent human evolution

  11. Functional reorganization of motor and limbic circuits after exercise training in a rat model of bilateral parkinsonism.

    PubMed

    Wang, Zhuo; Myers, Kalisa G; Guo, Yumei; Ocampo, Marco A; Pang, Raina D; Jakowec, Michael W; Holschneider, Daniel P

    2013-01-01

    Exercise training is widely used for neurorehabilitation of Parkinson's disease (PD). However, little is known about the functional reorganization of the injured brain after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise in a rat model of dopaminergic deafferentation (bilateral, dorsal striatal 6-hydroxydopamine lesions). One week after training, cerebral perfusion was mapped during treadmill walking or at rest using [(14)C]-iodoantipyrine autoradiography. Regional cerebral blood flow-related tissue radioactivity (rCBF) was analyzed in three-dimensionally reconstructed brains by statistical parametric mapping. In non-exercised rats, lesions resulted in persistent motor deficits. Compared to sham-lesioned rats, lesioned rats showed altered functional brain activation during walking, including: 1. hypoactivation of the striatum and motor cortex; 2. hyperactivation of non-lesioned areas in the basal ganglia-thalamocortical circuit; 3. functional recruitment of the red nucleus, superior colliculus and somatosensory cortex; 4. hyperactivation of the ventrolateral thalamus, cerebellar vermis and deep nuclei, suggesting recruitment of the cerebellar-thalamocortical circuit; 5. hyperactivation of limbic areas (amygdala, hippocampus, ventral striatum, septum, raphe, insula). These findings show remarkable similarities to imaging findings reported in PD patients. Exercise progressively improved motor deficits in lesioned rats, while increasing activation in dorsal striatum and rostral secondary motor cortex, attenuating a hyperemia of the zona incerta and eliciting a functional reorganization of regions participating in the cerebellar-thalamocortical circuit. Both lesions and exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral striatum, laterodorsal tegmental n., ventral pallidum), as well as in related paralimbic regions (septum, raphe, insula). Exercise, but not lesioning, resulted in decreases

  12. Functional Reorganization of Motor and Limbic Circuits after Exercise Training in a Rat Model of Bilateral Parkinsonism

    PubMed Central

    Wang, Zhuo; Myers, Kalisa G.; Guo, Yumei; Ocampo, Marco A.; Pang, Raina D.; Jakowec, Michael W.; Holschneider, Daniel P.

    2013-01-01

    Exercise training is widely used for neurorehabilitation of Parkinson’s disease (PD). However, little is known about the functional reorganization of the injured brain after long-term aerobic exercise. We examined the effects of 4 weeks of forced running wheel exercise in a rat model of dopaminergic deafferentation (bilateral, dorsal striatal 6-hydroxydopamine lesions). One week after training, cerebral perfusion was mapped during treadmill walking or at rest using [14C]-iodoantipyrine autoradiography. Regional cerebral blood flow-related tissue radioactivity (rCBF) was analyzed in three-dimensionally reconstructed brains by statistical parametric mapping. In non-exercised rats, lesions resulted in persistent motor deficits. Compared to sham-lesioned rats, lesioned rats showed altered functional brain activation during walking, including: 1. hypoactivation of the striatum and motor cortex; 2. hyperactivation of non-lesioned areas in the basal ganglia-thalamocortical circuit; 3. functional recruitment of the red nucleus, superior colliculus and somatosensory cortex; 4. hyperactivation of the ventrolateral thalamus, cerebellar vermis and deep nuclei, suggesting recruitment of the cerebellar-thalamocortical circuit; 5. hyperactivation of limbic areas (amygdala, hippocampus, ventral striatum, septum, raphe, insula). These findings show remarkable similarities to imaging findings reported in PD patients. Exercise progressively improved motor deficits in lesioned rats, while increasing activation in dorsal striatum and rostral secondary motor cortex, attenuating a hyperemia of the zona incerta and eliciting a functional reorganization of regions participating in the cerebellar-thalamocortical circuit. Both lesions and exercise increased activation in mesolimbic areas (amygdala, hippocampus, ventral striatum, laterodorsal tegmental n., ventral pallidum), as well as in related paralimbic regions (septum, raphe, insula). Exercise, but not lesioning, resulted in decreases

  13. The Limbic-Prefrontal Network Modulated by Electroacupuncture at CV4 and CV12

    PubMed Central

    Fang, Jiliang; Wang, Xiaoling; Liu, Hesheng; Wang, Yin; Zhou, Kehua; Hong, Yang; Liu, Jun; Wang, Lei; Xue, Chao; Song, Ming; Liu, Baoyan; Zhu, Bing

    2012-01-01

    fMRI studies showed that acupuncture could induce hemodynamic changes in brain networks. Many of these studies focused on whether specific acupoints could activate specific brain regions and were often limited to manual acupuncture at acupoints on the limbs. In this fMRI study, we investigated acupuncture's modulation effects on brain functional networks by electroacupuncture (EA) at acupoints on the midline of abdomen. Acupoints Guanyuan (CV4) and Zhongwan (CV12) were stimulated in 21 healthy volunteers. The needling sensations, brain activation, and functional connectivity were studied. We found that the limbic-prefrontal functional network was deactivated by EA at CV4 and CV12. More importantly, the local functional connectivity was significantly changed during EA stimulation, and the change persisted during the period after the stimulation. Although minor differences existed, both acupoints similarly modulated the limbic-prefrontal functional network, which is overlapped with the functional circuits associated with emotional and cognitive regulation. PMID:22291848

  14. 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)

  15. 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.

  16. Paraneoplastic limbic encephalitis: clinico-pathological correlations.

    PubMed Central

    Bakheit, A M; Kennedy, P G; Behan, P O

    1990-01-01

    Three new cases of limbic encephalitis in association with malignancy are reported. The literature on this condition is reviewed and the clinical, laboratory and histopathological features of cases proven at necropsy are correlated. The possible pathogenic mechanism of this disorder is discussed. PMID:1963440

  17. Stereotactic limbic leucotomy: surgical technique

    PubMed Central

    Richardson, Alan

    1973-01-01

    The requirements for modern psychosurgery are safety and accuracy. Stereotactic techniques give the geometric accuracy and stimulation gives physiological information, which is important in determining lesion sites or at least lesion symmetry. The process whereby focal brain destruction is produced is ideally by a freezing probe, but equally effectively by coagulation. A number of small lesions is thus required. This at present is unavoidable if side effects are to be obviated. Careful continuing assessment of results is necessary to validate any surgical procedure. ImagesFig. 1Fig. 2Fig. 3Fig. 4 PMID:4618905

  18. Impaired White Matter Connections of the Limbic System Networks Associated with Impaired Emotional Memory in Alzheimer's Disease

    PubMed Central

    Li, Xiaoshu; Wang, Haibao; Tian, Yanghua; Zhou, Shanshan; Li, Xiaohu; Wang, Kai; Yu, Yongqiang

    2016-01-01

    Background: Discrepancies persist regarding retainment of emotional enhancement of memory (EEM) in mild cognitive impairment (MCI) and early Alzheimer's disease (AD) patients.In addition, the neural mechanisms are still poorly understood, little is known about emotional memory related changes in white matter (WM). Objective: To observe whether EEM is absent in amnestic MCI (aMCI) and AD patients, and to investigate if emotional memory is associated with WM connections and gray matters (GM) of the limbic system networks. Methods: Twenty-one AD patients, 20 aMCI patients and 25 normal controls participated in emotional picture recognition tests and MRI scanning. Tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM) methods were used to determine white and gray matter changes of patients. Fourteen regions of interest (ROI) of WM and 20 ROIs of GM were then selected for the correlation analyses with behavioral scores. Results: The EEM effect was lost in AD patients. Both white and gray matter of the limbic system networks were impaired in AD patients. Significant correlations or tendencies between the bilateral uncinate fasciculus, corpus callosum (genu and body), left cingulum bundle, left parahippocampal WM and the recognition sensitivity of emotional valence pictures, and significant correlations or tendencies between the splenium of corpus callosum, left cingulum bundle, left crus of fornix and stria terminalis and the recognition sensitivity of EEM were found. The volume of left amygdala, bilateral insula, medial frontal lobe, anterior and middle cingulum gyrus were positively correlated with the recognition sensitivity of emotional photos, and the right precuneus was positively correlated with the negative EEM effect. However, the affected brain areas of aMCI patients were more localized, and aMCI patients benefited only from positive stimuli. Conclusion: There are impairments of the limbic system networks of AD patients. Damaged WM connections

  19. Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study.

    PubMed

    Qi, Ji; Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Qu, Shanshan

    2014-02-01

    Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revealed activation in right parietal lobe (Brodmann areas 7 and 19), the right temporal lobe (Brodmann area 39), the right limbic lobe (Brodmann area 23) and bilateral occipital lobes (Brodmann area 18). Furthermore, inhibition of bilateral frontal lobes (Brodmann area 4, 6, and 45), right parietal lobe (Brodmann areas 1 and 5) and left temporal lobe (Brodmann area 21) were observed in the true point group. Activation in the precuneus of right parietal lobe (Brodmann area 7) and inhibition of the left superior frontal gyrus (Brodmann area 10) was observed in the sham group. Compared with sham acupuncture, acupuncture at Waiguan in stroke patients inhibited Brodmann area 5 on the healthy side. Results indicated that the altered specificity of sensation-associated cortex (Brodmann area 5) is possibly associated with a central mechanism of acupuncture at Waiguan for stroke patients.

  20. Brain Areas Responsible for Vigilance: An EEG Source Imaging Study.

    PubMed

    Kim, Jung-Hoon; Kim, Do-Won; Im, Chang-Hwan

    2017-01-04

    Vigilance, sometimes referred to as sustained attention, is an important type of human attention as it is closely associated with cognitive activities required in various daily-life situations. Although many researchers have investigated which brain areas control the maintenance of vigilance, findings have been inconsistent. We hypothesized that this inconsistency might be due to the use of different experimental paradigms in the various studies. We found that most of the previous studies used paradigms that included specific cognitive tasks requiring a high cognitive load, which could complicate identification of brain areas associated only with vigilance. To minimize the influence of cognitive processes other than vigilance on the analysis results, we adopted the d2-test of attention, which is a well-known neuropsychological test of attention that does not require high cognitive load, and searched for brain areas at which EEG source activities were temporally correlated with fluctuation of vigilance over a prolonged period of time. EEG experiments conducted with 31 young adults showed that left prefrontal cortex activity was significantly correlated with vigilance variation in the delta, beta1, beta2, and gamma frequency bands, but not the theta and alpha frequency bands. Our study results suggest that the left prefrontal cortex plays a key role in vigilance modulation, and can therefore be used to monitor individual vigilance changes over time or serve as a potential target of noninvasive brain stimulation.

  1. How Localized are Language Brain Areas? A Review of Brodmann Areas Involvement in Oral Language.

    PubMed

    Ardila, Alfredo; Bernal, Byron; Rosselli, Monica

    2016-02-01

    The interest in understanding how language is "localized" in the brain has existed for centuries. Departing from seven meta-analytic studies of functional magnetic resonance imaging activity during the performance of different language activities, it is proposed here that there are two different language networks in the brain: first, a language reception/understanding system, including a "core Wernicke's area" involved in word recognition (BA21, BA22, BA41, and BA42), and a fringe or peripheral area ("extended Wernicke's area:" BA20, BA37, BA38, BA39, and BA40) involved in language associations (associating words with other information); second, a language production system ("Broca's complex:" BA44, BA45, and also BA46, BA47, partially BA6-mainly its mesial supplementary motor area-and extending toward the basal ganglia and the thalamus). This paper additionally proposes that the insula (BA13) plays a certain coordinating role in interconnecting these two brain language systems.

  2. 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.

  3. Wired for behaviors: from development to function of innate limbic system circuitry

    PubMed Central

    Sokolowski, Katie; Corbin, Joshua G.

    2012-01-01

    The limbic system of the brain regulates a number of behaviors that are essential for the survival of all vertebrate species including humans. The limbic system predominantly controls appropriate responses to stimuli with social, emotional, or motivational salience, which includes innate behaviors such as mating, aggression, and defense. Activation of circuits regulating these innate behaviors begins in the periphery with sensory stimulation (primarily via the olfactory system in rodents), and is then processed in the brain by a set of delineated structures that primarily includes the amygdala and hypothalamus. While the basic neuroanatomy of these connections is well-established, much remains unknown about how information is processed within innate circuits and how genetic hierarchies regulate development and function of these circuits. Utilizing innovative technologies including channel rhodopsin-based circuit manipulation and genetic manipulation in rodents, recent studies have begun to answer these central questions. In this article we review the current understanding of how limbic circuits regulate sexually dimorphic behaviors and how these circuits are established and shaped during pre- and post-natal development. We also discuss how understanding developmental processes of innate circuit formation may inform behavioral alterations observed in neurodevelopmental disorders, such as autism spectrum disorders, which are characterized by limbic system dysfunction. PMID:22557946

  4. Metallothionein-I induction by stress in specific brain areas.

    PubMed

    Hidalgo, J; Campmany, L; Martí, O; Armario, A

    1991-10-01

    The distribution of metallothionein-I (MT) in several areas of the brain and its induction by immobilization stress has been studied in the rat. MT content was highest in hippocampus and midbrain and lowest in frontal cortex and pons plus medulla oblongata. Immobilization stress for 18 hours (which was accompanied by food and water deprivation) significantly increased MT levels in the frontal cortex, pons plus medulla oblongata and hypothalamus, but not in midbrain and hippocampus. The effect of stress on MT levels was specific as food and water deprivation along had no significant effect on MT levels in any of the brain areas studied. The effect of stress on MT levels was independent of changes in cytosolic Zn content; this was generally unaffected by stress or food and water deprivation but decreased in pons plus medulla oblongata from stressed rats. The results suggest that MT is induced more significantly in the brain areas that are usually involved in the response of animals to stress.

  5. Activated and deactivated functional brain areas in the Deqi state

    PubMed Central

    Huang, Yong; Zeng, Tongjun; Zhang, Guifeng; Li, Ganlong; Lu, Na; Lai, Xinsheng; Lu, Yangjia; Chen, Jiarong

    2012-01-01

    We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects during acupuncture. Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, thalamus and red nucleus. True needling also deactivated Brodmann areas 1, 2, 3, 4, 5, 6, 7, 9, 10, 18, 24, 31, 40 and 46. PMID:25538761

  6. Maternal sensitivity, infant limbic structure volume and functional connectivity: a preliminary study

    PubMed Central

    Rifkin-Graboi, A; Kong, L; Sim, L W; Sanmugam, S; Broekman, B F P; Chen, H; Wong, E; Kwek, K; Saw, S-M; Chong, Y-S; Gluckman, P D; Fortier, M V; Pederson, D; Meaney, M J; Qiu, A

    2015-01-01

    Mechanisms underlying the profound parental effects on cognitive, emotional and social development in humans remain poorly understood. Studies with nonhuman models suggest variations in parental care affect the limbic system, influential to learning, autobiography and emotional regulation. In some research, nonoptimal care relates to decreases in neurogenesis, although other work suggests early-postnatal social adversity accelerates the maturation of limbic structures associated with emotional learning. We explored whether maternal sensitivity predicts human limbic system development and functional connectivity patterns in a small sample of human infants. When infants were 6 months of age, 20 mother–infant dyads attended a laboratory-based observational session and the infants underwent neuroimaging at the same age. After considering age at imaging, household income and postnatal maternal anxiety, regression analyses demonstrated significant indirect associations between maternal sensitivity and bilateral hippocampal volume at six months, with the majority of associations between sensitivity and the amygdala demonstrating similar indirect, but not significant results. Moreover, functional analyses revealed direct associations between maternal sensitivity and connectivity between the hippocampus and areas important for emotional regulation and socio-emotional functioning. Sensitivity additionally predicted indirect associations between limbic structures and regions related to autobiographical memory. Our volumetric results are consistent with research indicating accelerated limbic development in response to early social adversity, and in combination with our functional results, if replicated in a larger sample, may suggest that subtle, but important, variations in maternal care influence neuroanatomical trajectories important to future cognitive and emotional functioning. PMID:26506054

  7. [Paraneoplastic limbic encephalitis with positive anti-RI antibodies and mediastinal seminoma].

    PubMed

    Launay, M; Bozzolo, E; Venissac, N; Delmont, E; Fredenrich, A; Thomas, P

    2008-01-01

    We report the case of a 49-year-old man who was admitted for progressive behaviorial disorders with frontal elements. There was no sensorial nor motor deficiency. Clinical examination revealed android obesity, cutaneous and mucous paleness, pubic and axillary depilation and gynecomastia. Encephalic MRI found a lesion of the left amygdalian region with high T2 intensity and low T1 intensity associated with gadolinium-enhancement. Cerebrospinal fluid analysis showed a lymphocytic meningitis. Panhypopituitarism was found on the endocrine investigations. Anti-RI antibodies were positive, leading to the diagnosis of paraneoplastic limbic encephalitis. The CT-scan showed a node of the lower part of the thymic area. Surgical resection revealed an ectopic mediastinal seminoma. The evolution consisted of paraneoplastic fever and crossed-syndrome with right hemiparesia and left common oculomotor nerve paralysis. Treatment was completed by two cycles of carboplatin, corticosteroids and substitutive opotherapy. Paraneoplastic fever disappeared, but behavioral disorders and palsy remain unchanged. The patient died two years later in a bedridden state. This case of paraneoplastic limbic encephalitis associated with positive anti-RI antibodies and mediastinal seminoma is exceptional and has not to our knowledge been described in the literature. Cancers usually associated with anti-RI antibody are breast and lung cancer. Paraneoplastic limbic encephalitis is not the classical clinical presentation, which usually is brainstem encephalitis. Hypothalamic involvement, uncommon in paraneoplastic limbic encephalitis is mainly associated with positive antineuronal anti-Ma2 antibodies. Finally, the gadolinium enhancement on encephalic MRI is unusual in paraneoplastic limbic encephalitis.

  8. Testosterone affects language areas of the adult human brain.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc.

  9. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  10. Neurocognitive Brain Response to Transient Impairment of Wernicke's Area

    PubMed Central

    Mason, Robert A.; Prat, Chantel S.; Just, Marcel Adam

    2014-01-01

    This study examined how the brain system adapts and reconfigures its information processing capabilities to maintain cognitive performance after a key cortical center [left posterior superior temporal gyrus (LSTGp)] is temporarily impaired during the performance of a language comprehension task. By applying repetitive transcranial magnetic stimulation (rTMS) to LSTGp and concurrently assessing the brain response with functional magnetic resonance imaging, we found that adaptation consisted of 1) increased synchronization between compensating regions coupled with a decrease in synchronization within the primary language network and 2) a decrease in activation at the rTMS site as well as in distal regions, followed by their recovery. The compensatory synchronization included 3 centers: The contralateral homolog (RSTGp) of the area receiving rTMS, areas adjacent to the rTMS site, and a region involved in discourse monitoring (medial frontal gyrus). This approach reveals some principles of network-level adaptation to trauma with potential application to traumatic brain injury, stroke, and seizure. PMID:23322403

  11. Selectivity to Translational Egomotion in Human Brain Motion Areas

    PubMed Central

    Pitzalis, Sabrina; Sdoia, Stefano; Bultrini, Alessandro; Committeri, Giorgia; Di Russo, Francesco; Fattori, Patrizia; Galletti, Claudio; Galati, Gaspare

    2013-01-01

    The optic flow generated when a person moves through the environment can be locally decomposed into several basic components, including radial, circular, translational and spiral motion. Since their analysis plays an important part in the visual perception and control of locomotion and posture it is likely that some brain regions in the primate dorsal visual pathway are specialized to distinguish among them. The aim of this study is to explore the sensitivity to different types of egomotion-compatible visual stimulations in the human motion-sensitive regions of the brain. Event-related fMRI experiments, 3D motion and wide-field stimulation, functional localizers and brain mapping methods were used to study the sensitivity of six distinct motion areas (V6, MT, MST+, V3A, CSv and an Intra-Parietal Sulcus motion [IPSmot] region) to different types of optic flow stimuli. Results show that only areas V6, MST+ and IPSmot are specialized in distinguishing among the various types of flow patterns, with a high response for the translational flow which was maximum in V6 and IPSmot and less marked in MST+. Given that during egomotion the translational optic flow conveys differential information about the near and far external objects, areas V6 and IPSmot likely process visual egomotion signals to extract information about the relative distance of objects with respect to the observer. Since area V6 is also involved in distinguishing object-motion from self-motion, it could provide information about location in space of moving and static objects during self-motion, particularly in a dynamically unstable environment. PMID:23577096

  12. A Novel Human Body Area Network for Brain Diseases Analysis.

    PubMed

    Lin, Kai; Xu, Tianlang

    2016-10-01

    Development of wireless sensor and mobile communication technology provide an unprecedented opportunity for realizing smart and interactive healthcare systems. Designing such systems aims to remotely monitor the health and diagnose the diseases for users. In this paper, we design a novel human body area network for brain diseases analysis, which is named BABDA. Considering the brain is one of the most complex organs in the human body, the BABDA system provides four function modules to ensure the high quality of the analysis result, which includes initial data collection, data correction, data transmission and comprehensive data analysis. The performance evaluation conducted in a realistic environment with several criteria shows the availability and practicability of the BABDA system.

  13. Chronic stress disrupts neural coherence between cortico-limbic structures

    PubMed Central

    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. PMID:23390414

  14. 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'.

  15. The electrophysiology of the olfactory-hippocampal circuit in the isolated and perfused adult mammalian brain in vitro.

    PubMed

    de Curtis, M; Paré, D; Llinás, R R

    1991-10-01

    The viability and general electrophysiological properties of the limbic system in the adult mammalian brain isolated and maintained in vitro by arterial perfusion are described. The isolated brain preparation combines the advantages of intact synaptic connectivity and accessibility of different areas of the encephalic mass with those of the in vitro approach, i.e., stability and control of the ionic environment. Extracellular field potential as well as intracellular recordings were performed at different levels in the limbic system of isolated adult guinea pig brains. The results demonstrate that in the piriform, entorhinal, and hippocampal cortices, the intrinsic electrical properties of individual cells as well as the spontaneous and evoked electrical activity in the neuronal ensembles they comprise, were virtually identical to those observed in vivo. The properties of the limbic system loop were determined.

  16. Limbic system pathologies associated with deficiencies and excesses of the trace elements iron, zinc, copper, and selenium.

    PubMed

    Torres-Vega, Adriana; Pliego-Rivero, Bernardo F; Otero-Ojeda, Gloria A; Gómez-Oliván, Leobardo M; Vieyra-Reyes, Patricia

    2012-12-01

    Deficiencies of nutrients such as amino acids, vitamins, lipids, and trace elements during gestation and early infanthood have strong deleterious effects on the development of the limbic system; these effects may be irreversible, even when adequate supplementation is provided at later developmental stages. Recent advances in the neurochemistry of biometals are increasingly establishing the roles of the trace elements iron, copper, zinc, and selenium in a variety of cell functions and are providing insight into the repercussions of deficiencies and excesses of these elements on the development of the central nervous system, especially the limbic system. The limbic system comprises diverse areas with high metabolic demands and differential storage of iron, copper, zinc, and selenium. This review summarizes available evidence suggesting the involvement of these trace elements in pathological disorders of the limbic system. © 2012 International Life Sciences Institute.

  17. Early life stress modulates oxytocin effects on limbic system during acute psychosocial stress.

    PubMed

    Grimm, Simone; Pestke, Karin; Feeser, Melanie; Aust, Sabine; Weigand, Anne; Wang, Jue; Wingenfeld, Katja; Pruessner, Jens C; La Marca, Roberto; Böker, Heinz; Bajbouj, Malek

    2014-11-01

    Early life stress (ELS) is associated with altered stress responsivity, structural and functional brain changes and an increased risk for the development of psychopathological conditions in later life. Due to its behavioral and physiological effects, the neuropeptide oxytocin (OXT) is a useful tool to investigate stress responsivity, even though the neurobiological underpinnings of its effects are still unknown. Here we investigate the effects of OXT on cortisol stress response and neural activity during psychosocial stress. Using functional magnetic resonance imaging in healthy subjects with and without a history of ELS, we found attenuated hormonal reactivity and significantly reduced limbic deactivation after OXT administration in subjects without a history of ELS. Subjects who experienced ELS showed both blunted stress reactivity and limbic deactivation during stress. Furthermore, in these subjects OXT had opposite effects with increased hormonal reactivity and increased limbic deactivation. Our results might implicate that reduced limbic deactivation and hypothalamic-pituitary-adrenal axis responsivity during psychosocial stress are markers for biological resilience after ELS. Effects of OXT in subjects with a history of maltreatment could therefore be considered detrimental and suggest careful consideration of OXT administration in such individuals. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Early life stress as an influence on limbic epilepsy: an hypothesis whose time has come?

    PubMed

    Koe, Amelia S; Jones, Nigel C; Salzberg, Michael R

    2009-01-01

    The pathogenesis of mesial temporal lobe epilepsy (MTLE), the most prevalent form of refractory focal epilepsy in adults, is thought to begin in early life, even though seizures may not commence until adolescence or adulthood. Amongst the range of early life factors implicated in MTLE causation (febrile seizures, traumatic brain injury, etc.), stress may be one important contributor. Early life stress is an a priori agent deserving study because of the large amount of neuroscientific data showing enduring effects on structure and function in hippocampus and amygdala, the key structures involved in MTLE. An emerging body of evidence directly tests hypotheses concerning early life stress and limbic epilepsy: early life stressors, such as maternal separation, have been shown to aggravate epileptogenesis in both status epilepticus and kindling models of limbic epilepsy. In addition to elucidating its influence on limbic epileptogenesis itself, the study of early life stress has the potential to shed light on the psychiatric disorder that accompanies MTLE. For many years, psychiatric comorbidity was viewed as an effect of epilepsy, mediated psychologically and/or neurobiologically. An alternative - or complementary - perspective is that of shared causation. Early life stress, implicated in the pathogenesis of several psychiatric disorders, may be one such causal factor. This paper aims to critically review the body of experimental evidence linking early life stress and epilepsy; to discuss the direct studies examining early life stress effects in current models of limbic seizures/epilepsy; and to suggest priorities for future research.

  19. Night-vision brain area in migratory songbirds

    PubMed Central

    Mouritsen, Henrik; Feenders, Gesa; Liedvogel, Miriam; Wada, Kazuhiro; Jarvis, Erich D.

    2005-01-01

    Twice each year, millions of night-migratory songbirds migrate thousands of kilometers. To find their way, they must process and integrate spatiotemporal information from a variety of cues including the Earth's magnetic field and the night-time starry sky. By using sensory-driven gene expression, we discovered that night-migratory songbirds possess a tight cluster of brain regions highly active only during night vision. This cluster, here named “cluster N,” is located at the dorsal surface of the brain and is adjacent to a known visual pathway. In contrast, neuronal activation of cluster N was not increased in nonmigratory birds during the night, and it disappeared in migrants when both eyes were covered. We suggest that in night-migratory songbirds cluster N is involved in enhanced night vision, and that it could be integrating vision-mediated magnetic and/or star compass information for night-time navigation. Our findings thus represent an anatomical and functional demonstration of a specific night-vision brain area. PMID:15928090

  20. Grey matter abnormalities within cortico-limbic-striatal circuits in acute and weight-restored anorexia nervosa patients.

    PubMed

    Friederich, Hans-Christoph; Walther, Stephan; Bendszus, Martin; Biller, Armin; Thomann, Philipp; Zeigermann, Susanne; Katus, Tobias; Brunner, Romuald; Zastrow, Arne; Herzog, Wolfgang

    2012-01-16

    Functional disturbances within cortico-striatal control systems have been implicated in the psychobiology (i.e. impaired cognitive-behavioral flexibility, perfectionist personality) of anorexia nervosa. The aim of the present study was to investigate the morphometry of brain regions within cortico-striatal networks in acute anorexia nervosa (AN) as well as long-term weight-restored anorexia nervosa (AN-WR) patients. A total of 39 participants: 12 AN, 13 AN-WR patients, and 14 healthy controls (HC) underwent high-resolution, T1-weighted magnetic resonance imaging (MRI), a cognitive-behavioral flexibility task, and a psychometric assessment. Group differences in local grey matter volume (GMV) were analyzed using whole brain voxel-based morphometry (VBM) and brain-atlas based automatic volumetry computation (IBASPM). Individual differences in total GMV were considered as a covariate in all analyses. In the regional brain morphometry, AN patients, as compared to HC, showed decreased GMVs (VBM and volumetry) in the anterior cingulate cortex (ACC), the supplementary motor area (SMA), and in subcortical regions (amygdala, putamen: VBM only). AN-WR compared to HC showed decreased GMV (VBM and volumetry) in the ACC and SMA, whereas GMV of the subcortical region showed no differences. The findings of the study suggest that structural abnormalities of the ACC and SMA were independent of the disease stage, whereas subcortical limbic-striatal changes were state dependent. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. 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 Central

    Lee, Tae-Ho; Telzer, Eva H.

    2016-01-01

    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. PMID:27344035

  2. Pilomotor seizures: an autonomic semiology of limbic encephalitis?

    PubMed

    Rocamora, Rodrigo; Becerra, Juan L; Fossas, Pilar; Gomez, María; Vivanco-Hidalgo, Rosa M; Mauri, José A; Molins, Albert

    2014-09-01

    Ictal piloerection is an infrequent seizure semiology that is commonly overlooked as an ictal epileptic manifestation. Piloerection is considered to be principally caused by temporal lobe activity although frontal and hypothalamic seizure origins have been reported. The described etiology has shown a wide variety of structural causes such as mesial temporal sclerosis, tumors, posttraumatic, cavernomas and cryptogenic epilepsies. We retrospectively reviewed the incidence of ictal piloerection in the clinical records of patients who underwent video-EEG monitoring (VEEGM) between 2007 and 2013 in a multicenter cooperative study. All patients presented refractory epilepsies and were evaluated with a protocol that included brain MRI, neuropsychology and VEEGM. A total of 766 patients were evaluated in four tertiary centers in Spain. Five patients showed piloerection as principal seizure semiology (prevalence 0.65%). The mean age at seizure onset was 39.6 years and the average epilepsy duration was 5.2 years (range 2-14) before diagnosis. Four patients were additionally examined with FDG-PET and/or SPECT-SISCOM. All presented temporal lobe epilepsy (TLE), three right-sided and two left-sided. A typical unilateral hippocampal sclerosis was described in 3 cases. The etiology detected in all cases was limbic encephalitis. Three had LGI1, one anti-Hu, and another Ma2 antibodies. Our series describes a so far not well-recognized autoimmune association of pilomotor seizures to limbic encephalitis. This etiology should be ruled out through a comprehensive diagnostic work-up even in cases of long-lasting TLE with typical hippocampal atrophy on MRI. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  3. 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.

  4. 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.

  5. Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro.

    PubMed

    Avoli, Massimo; D'Antuono, Margherita; Louvel, Jacques; Köhling, Rüdiger; Biagini, Giuseppe; Pumain, René; D'Arcangelo, Giovanna; Tancredi, Virginia

    2002-10-01

    Seizures in patients presenting with mesial temporal lobe epilepsy result from the interaction among neuronal networks in limbic structures such as the hippocampus, amygdala and entorhinal cortex. Mesial temporal lobe epilepsy, one of the most common forms of partial epilepsy in adulthood, is generally accompanied by a pattern of brain damage known as mesial temporal sclerosis. Limbic seizures can be mimicked in vitro using preparations of combined hippocampus-entorhinal cortex slices perfused with artificial cerebrospinal fluid containing convulsants or nominally zero Mg(2+), in order to produce epileptiform synchronization. Here, we summarize experimental evidence obtained in such slices from rodents. These data indicate that in control animals: (i) prolonged, NMDA receptor-dependent epileptiform discharges, resembling electrographic limbic seizures, originate in the entorhinal cortex from where they propagate to the hippocampus via the perforant path-dentate gyrus route; (ii) the initiation and maintenance of these ictal discharges is paradoxically contributed by GABA (mainly type A) receptor-mediated mechanisms; and (iii) CA3 outputs, which relay a continuous pattern of interictal discharge at approximately 1Hz, control rather than sustain ictal discharge generation in entorhinal cortex. Recent work indicates that such a control is weakened in the pilocarpine model of epilepsy (presumably as a result of CA3 cell damage). In addition, in these experiments electrographic seizure activity spreads directly to the CA1-subiculum regions through the temporoammonic pathway. Studies reviewed here indicate that these changes in network interactions, along with other mechanisms of synaptic plasticity (e.g. axonal sprouting, decreased activation of interneurons, upregulation of bursting neurons) can confer to the epileptic, damaged limbic system, the ability to produce recurrent limbic seizures as seen in patients with mesial temporal lobe epilepsy.

  6. Encoding-based brain-computer interface controlled by non-motor area of rat brain.

    PubMed

    Lang, Yiran; Du, Ping; Shin, Hyung-Cheul

    2011-09-01

    As the needs of disabled patients are increasingly recognized in society, researchers have begun to use single neuron activity to construct brain-computer interfaces (BCI), designed to facilitate the daily lives of individuals with physical disabilities. BCI systems typically allow users to control computer programs or external devices via signals produced in the motor or pre-motor areas of the brain, rather than producing actual motor movements. However, impairments in these brain areas can hinder the application of BCI. The current paper demonstrates the feasibility of a one-dimensional (1D) machine controlled by rat prefrontal cortex (PFC) neurons using an encoding method. In this novel system, rats are able to quench thirst by varying neuronal firing rate in the PFC to manipulate a water dish that can rotate in 1D. The results revealed that control commands generated by an appropriate firing frequency in rat PFC exhibited performance improvements with practice, indicated by increasing water-drinking duration and frequency. These results demonstrated that it is possible for rats to understand an encoding-based BCI system and control a 1D machine using PFC activity to obtain reward.

  7. Age-Related Differences in the Brain Areas outside the Classical Language Areas among Adults Using Category Decision Task

    ERIC Educational Resources Information Center

    Cho, Yong Won; Song, Hui-Jin; Lee, Jae Jun; Lee, Joo Hwa; Lee, Hui Joong; Yi, Sang Doe; Chang, Hyuk Won; Berl, Madison M.; Gaillard, William D.; Chang, Yongmin

    2012-01-01

    Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that…

  8. Age-Related Differences in the Brain Areas outside the Classical Language Areas among Adults Using Category Decision Task

    ERIC Educational Resources Information Center

    Cho, Yong Won; Song, Hui-Jin; Lee, Jae Jun; Lee, Joo Hwa; Lee, Hui Joong; Yi, Sang Doe; Chang, Hyuk Won; Berl, Madison M.; Gaillard, William D.; Chang, Yongmin

    2012-01-01

    Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that…

  9. Neurophysiological responses to stressful motion and anti-motion sickness drugs as mediated by the limbic system

    NASA Technical Reports Server (NTRS)

    Kohl, R. L.; Odell, S.

    1982-01-01

    Performance is characterized in terms of attention and memory, categorizing extrinsic mechanism mediated by ACTH, norepinephrine and dopamine, and intrinsic mechanisms as cholinergic. The cholinergic role in memory and performance was viewed from within the limbic system and related to volitional influences of frontal cortical afferents and behavioral responses of hypothalamic and reticular system efferents. The inhibitory influence of the hippocampus on the autonomic and hormonal responses mediated through the hypothalamus, pituitary, and brain stem are correlated with the actions of such anti-motion sickness drugs as scopolamine and amphetamine. These drugs appear to exert their effects on motion sickness symptomatology through diverse though synergistic neurochemical mechanisms involving the septohippocampal pathway and other limbic system structures. The particular impact of the limbic system on an animal's behavioral and hormonal responses to stress is influenced by ACTH, cortisol, scopolamine, and amphetamine.

  10. NCAN Cross-Disorder Risk Variant Is Associated With Limbic Gray Matter Deficits in Healthy Subjects and Major Depression.

    PubMed

    Dannlowski, Udo; Kugel, Harald; Grotegerd, Dominik; Redlich, Ronny; Suchy, Janina; Opel, Nils; Suslow, Thomas; Konrad, Carsten; Ohrmann, Patricia; Bauer, Jochen; Kircher, Tilo; Krug, Axel; Jansen, Andreas; Baune, Bernhard T; Heindel, Walter; Domschke, Katharina; Forstner, Andreas J; Nöthen, Markus M; Treutlein, Jens; Arolt, Volker; Hohoff, Christa; Rietschel, Marcella; Witt, Stephanie H

    2015-10-01

    Genome-wide association studies have reported an association between NCAN rs1064395 genotype and bipolar disorder. This association was later extended to schizophrenia and major depression. However, the neurobiological underpinnings of these associations are poorly understood. NCAN is implicated in neuronal plasticity and expressed in subcortical brain areas, such as the amygdala and hippocampus, which are critically involved in dysfunctional emotion processing and regulation across diagnostic boundaries. We hypothesized that the NCAN risk variant is associated with reduced gray matter volumes in these areas. Gray matter structure was assessed by voxel-based morphometry on structural MRI data in two independent German samples (healthy subjects, n=512; depressed inpatients, n=171). All participants were genotyped for NCAN rs1064395. Hippocampal and amygdala region-of-interest analyses were performed within each sample. In addition, whole-brain data from the combined sample were analyzed. Risk (A)-allele carriers showed reduced amygdala and hippocampal gray matter volumes in both cohorts with a remarkable spatial overlap. In the combined sample, genotype effects observed for the amygdala and hippocampus survived correction for entire brain volume. Further effects were also observed in the left orbitofrontal cortex and the cerebellum/fusiform gyrus. We conclude that NCAN genotype is associated with limbic gray matter alterations in healthy and depressed subjects in brain areas implicated in emotion perception and regulation. The present data suggest that NCAN forms susceptibility to neurostructural deficits in the amygdala, hippocampus, and prefrontal areas independent of disease, which might lead to disorder onset in the presence of other genetic or environmental risk factors.

  11. NCAN Cross-Disorder Risk Variant Is Associated With Limbic Gray Matter Deficits in Healthy Subjects and Major Depression

    PubMed Central

    Dannlowski, Udo; Kugel, Harald; Grotegerd, Dominik; Redlich, Ronny; Suchy, Janina; Opel, Nils; Suslow, Thomas; Konrad, Carsten; Ohrmann, Patricia; Bauer, Jochen; Kircher, Tilo; Krug, Axel; Jansen, Andreas; Baune, Bernhard T; Heindel, Walter; Domschke, Katharina; Forstner, Andreas J; Nöthen, Markus M; Treutlein, Jens; Arolt, Volker; Hohoff, Christa; Rietschel, Marcella; Witt, Stephanie H

    2015-01-01

    Genome-wide association studies have reported an association between NCAN rs1064395 genotype and bipolar disorder. This association was later extended to schizophrenia and major depression. However, the neurobiological underpinnings of these associations are poorly understood. NCAN is implicated in neuronal plasticity and expressed in subcortical brain areas, such as the amygdala and hippocampus, which are critically involved in dysfunctional emotion processing and regulation across diagnostic boundaries. We hypothesized that the NCAN risk variant is associated with reduced gray matter volumes in these areas. Gray matter structure was assessed by voxel-based morphometry on structural MRI data in two independent German samples (healthy subjects, n=512; depressed inpatients, n=171). All participants were genotyped for NCAN rs1064395. Hippocampal and amygdala region-of-interest analyses were performed within each sample. In addition, whole-brain data from the combined sample were analyzed. Risk (A)-allele carriers showed reduced amygdala and hippocampal gray matter volumes in both cohorts with a remarkable spatial overlap. In the combined sample, genotype effects observed for the amygdala and hippocampus survived correction for entire brain volume. Further effects were also observed in the left orbitofrontal cortex and the cerebellum/fusiform gyrus. We conclude that NCAN genotype is associated with limbic gray matter alterations in healthy and depressed subjects in brain areas implicated in emotion perception and regulation. The present data suggest that NCAN forms susceptibility to neurostructural deficits in the amygdala, hippocampus, and prefrontal areas independent of disease, which might lead to disorder onset in the presence of other genetic or environmental risk factors. PMID:25801500

  12. 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.

  13. Diurnal cortisol amplitude and fronto-limbic activity in response to stressful stimuli.

    PubMed

    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

    2009-06-01

    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.

  14. Individual Human Brain Areas Can Be Identified from Their Characteristic Spectral Activation Fingerprints

    PubMed Central

    Keitel, Anne; Gross, Joachim

    2016-01-01

    The human brain can be parcellated into diverse anatomical areas. We investigated whether rhythmic brain activity in these areas is characteristic and can be used for automatic classification. To this end, resting-state MEG data of 22 healthy adults was analysed. Power spectra of 1-s long data segments for atlas-defined brain areas were clustered into spectral profiles (“fingerprints”), using k-means and Gaussian mixture (GM) modelling. We demonstrate that individual areas can be identified from these spectral profiles with high accuracy. Our results suggest that each brain area engages in different spectral modes that are characteristic for individual areas. Clustering of brain areas according to similarity of spectral profiles reveals well-known brain networks. Furthermore, we demonstrate task-specific modulations of auditory spectral profiles during auditory processing. These findings have important implications for the classification of regional spectral activity and allow for novel approaches in neuroimaging and neurostimulation in health and disease. PMID:27355236

  15. Alcoholism and Dampened Temporal Limbic Activation to Emotional Faces

    PubMed Central

    Marinkovic, Ksenija; Oscar-Berman, Marlene; Urban, Trinity; O’Reilly, Cara E.; Howard, Julie A.; Sawyer, Kayle; Harris, Gordon J.

    2013-01-01

    Background Excessive chronic drinking is accompanied by a broad spectrum of emotional changes ranging from apathy and emotional flatness to deficits in comprehending emotional information, but their neural bases are poorly understood. Methods Emotional abnormalities associated with alcoholism were examined with functional magnetic resonance imaging in abstinent long-term alcoholic men in comparison to healthy demographically matched controls. Participants were presented with emotionally valenced words and photographs of faces during deep (semantic) and shallow (perceptual) encoding tasks followed by recognition. Results Overall, faces evoked stronger activation than words, with the expected material-specific laterality (left hemisphere for words, and right for faces) and depth of processing effects. However, whereas control participants showed stronger activation in the amygdala and hippocampus when viewing faces with emotional (relative to neutral) expressions, the alcoholics responded in an undifferentiated manner to all facial expressions. In the alcoholic participants, amygdala activity was inversely correlated with an increase in lateral prefrontal activity as a function of their behavioral deficits. Prefrontal modulation of emotional function as a compensation for the blunted amygdala activity during a socially relevant face appraisal task is in agreement with a distributed network engagement during emotional face processing. Conclusions Deficient activation of amygdala and hippocampus may underlie impaired processing of emotional faces associated with long-term alcoholism and may be a part of the wide array of behavioral problems including disinhibition, concurring with previously documented interpersonal difficulties in this population. Furthermore, the results suggest that alcoholics may rely on prefrontal rather than temporal limbic areas in order to compensate for reduced limbic responsivity and to maintain behavioral adequacy when faced with emotionally

  16. Targeted areas for improving health literacy after traumatic brain injury.

    PubMed

    Moore, Megan; Kiatchai, Taniga; Ayyagari, Rajiv C; Vavilala, Monica S

    2017-08-17

    To develop a framework to identify targeted areas for improving health literacy for caregivers after traumatic brain injury (TBI). Qualitative study using inductive and deductive qualitative content analysis was conducted in a large, urban, level I trauma centre. Interviews were conducted with 23 caregivers of persons with TBI. Participants' perspectives on communication and preparation for discharge were explored and understanding of commonly used words and discharge instructions were assessed. Four types of communication patterns were identified: formal, informal, indirect and caregiver-initiated. Informal and caregiver-initiated communication were the most common. All caregivers reported confusion about their family member's condition, care plan or discharge plan. Caregivers were not able to define commonly used terms in discharge instructions, and were confused by formatting and medical language. Caregivers were not aware of expected caregiving roles upon discharge. Conceptualizing findings within a family-centred care model, we offer specific strategies to improve health communication and caregiver capacity building to enhance health literacy. Health literacy and caregiver capacity to care for loved ones with TBI after hospital discharge is low. We offer specific target areas for improvement in verbal and written communication and capacity building that take into account provider, patient and family characteristics.

  17. Mapping the visual brain areas susceptible to phosphene induction through brain stimulation.

    PubMed

    Schaeffner, Lukas F; Welchman, Andrew E

    2017-01-01

    Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique whose effects on neural activity can be uncertain. Within the visual cortex, phosphenes are a useful marker of TMS: They indicate the induction of neural activation that propagates and creates a conscious percept. However, we currently do not know how susceptible different areas of the visual cortex are to TMS-induced phosphenes. In this study, we systematically map out locations in the visual cortex where stimulation triggered phosphenes. We relate this to the retinotopic organization and the location of object- and motion-selective areas, identified by functional magnetic resonance imaging (fMRI) measurements. Our results show that TMS can reliably induce phosphenes in early (V1, V2d, and V2v) and dorsal (V3d and V3a) visual areas close to the interhemispheric cleft. However, phosphenes are less likely in more lateral locations (hMT+/V5 and LOC). This suggests that early and dorsal visual areas are particularly amenable to TMS and that TMS can be used to probe the functional role of these areas.

  18. [The typological characteristics of higher nervous activity in dogs and the maxima of the cross-correlation function between the electrical activities of the frontal cortex and the brain limbic systems].

    PubMed

    Chilingarian, L I

    1999-01-01

    Electrical activity of the frontal cortex, dorsal hippocampus, basolateral amygdala and lateral hypothalamus was recorded in eight dogs with chronically implanted electrodes. Mean values of the maxima of crosscorrelation function (MCCF) between electrical potentials in the theta, alpha and beta-2 ranges were used as a basis for assessment of conditions for interaction between these structures. Typological features of the higher nervous activity were assessed by the animal performance under conditions of free choice of the reinforcement mode of a conditioned stimulus: either high probable but of low alimentary quality or with low probability but more valuable. The mean MCCF values in the theta range were higher than in the other ranges. The brain structure which had the high MCCF in the theta-range, at least, with two of the structures under study was considered as "dominant". It was shown that hippocampus was the dominant structure for melancholic dogs, the frontal cortex was in phlegmatics. The hypothalamus was shown to be the "dominant structure" in both sanguine and choleric animals, but, for the most part, its activity was correlated with different structures. Thus, conditions for interaction between the frontal cortex, hippocampus, amygdala and hypothalamus seem to be an important factor, which determines typological features of the higher nervous activity of dogs.

  19. 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.

  20. Can memories kindle nonconvulsive behavioral seizures in humans? Case report exemplifying the "limbic psychotic trigger reaction".

    PubMed

    Pontius, Anneliese A; Wieser, Heinz-Gregor

    2004-10-01

    We present three hypotheses-(1) the limbic psychotic trigger reaction (LPTR) is a form of nonconvulsive behavioral seizures (NCBS), (2) kindling may occur in the LPTR, and (3) kindling may occur with memory stimuli-and report a case that may exemplify a LPTR kindled by memory and triggered by light and smell. The LPTR has a primate model, in which NCBS are kindled by intermittent exposure to actual subthreshold stimuli. In humans, we propose that such triggering stimuli can be revived by memory alone. Thus, individualized stimuli can trigger partial limbic seizures or seizure-like bizarre episodes with a transient loss of frontal control functions. We present a case of paroxysmal episodes of out-of-character, bizarre, unplanned nonvoluntary acts that occurred with flat affect and without drive motivation (e.g., "fire setting"). Implicated is a transient state of limbic "paleo-consciousness" with preserved memory, autonomic arousal, and first-time brief psychosis (e.g., olfactory, visual hallucinations and depersonalization with olfactory attributes). As in kindled primates, LPTR patients do not show a consistent pattern of morphological brain abnormality; half have had an abnormal electroencephalogram, computed tomography scan, or magnetic resonance image at some time during their lives, and half (including the new patient) have had closed head injuries.

  1. Dynamics of rabbit brain edema in focal lesion and perilesion area after traumatic brain injury: a MRI study.

    PubMed

    Wei, Xiao-Er; Zhang, Yu-Zhen; Li, Yue-Hua; Li, Ming-Hua; Li, Wen-Bin

    2012-09-20

    To understand the dynamics of brain edema in different areas after traumatic brain injury (TBI) in rabbit, we used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) to monitor blood-brain barrier (BBB) permeability and cytotoxic brain edema after weight drop-induced TBI in rabbit. The dynamics of BBB permeability and brain edema were quantified using K(trans) and apparent diffusion coefficient (ADC) in the focal and perifocal lesion areas, as well as the area contralateral to the lesion. In the focal lesion area, K(trans) began to increase at 3 h post-TBI, peaked at 3 days, and decreased gradually while remaining higher than sham injury animals at 7 and 30 days. ADC was more variable, increased slightly at 3 h, decreased to its lowest value at 7 days, then increased to a peak at 30 days. In the perifocal lesion area, K(trans) began to increase at 1 day, peaked at 3-7 days, and returned to control level by 30 days. ADC showed a trend to increase at 1 day, followed by a continuous increase thereafter. In the contralateral area, no changes in K(trans) and ADC were observed at any time-point. These data demonstrate that different types of brain edema predominate in the focal and perifocal lesion areas. Specifically cytotoxic edema was predominant in the focal lesion area while vasogenic edema predominated in the perifocal area in acute phase. Furthermore, secondary opening of the BBB after TBI may appear if secondary injury is not controlled. BBB damage may be a driving force for cytotoxic brain edema and could be a new target for TBI intervention.

  2. 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.

  3. 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.

  4. Effects of Swimming Exercise on Limbic and Motor Cortex Neurogenesis in the Kainate-Lesion Model of Temporal Lobe Epilepsy

    PubMed Central

    Gorantla, Vasavi R.; Sirigiri, Amulya; Volkova, Yulia A.; Millis, Richard M.

    2016-01-01

    Temporal lobe epilepsy (TLE) is a common neurological disease and antiseizure medication is often inadequate for preventing apoptotic cell death. Aerobic swimming exercise (EX) augments neurogenesis in rats when initiated immediately in the postictal period. This study tests the hypothesis that aerobic exercise also augments neurogenesis over the long term. Male Wistar rats (age of 4 months) were subjected to chemical lesioning using KA and to an EX intervention consisting of a 30 d period of daily swimming for 15 min, in one experiment immediately after KA lesioning (immediate exposure) and in a second experiment after a 60 d period of normal activity (delayed exposure). Morphometric counting of neuron numbers (NN) and dendritic branch points and intersections (DDBPI) was performed in the CA1, CA3, and dentate regions of hippocampus, in basolateral nucleus of amygdala, and in several areas of motor cortex. EX increased NN and DDBPI in the normal control and the KA-lesioned rats in all four limbic and motor cortex areas studied, after both immediate and 60 d delayed exposures to exercise. These findings suggest that, after temporal lobe epileptic seizures in rats, swimming exercise may improve neural plasticity in areas of the brain involved with emotional regulation and motor coordination, even if the exercise treatment is delayed. PMID:27313873

  5. Effects of Swimming Exercise on Limbic and Motor Cortex Neurogenesis in the Kainate-Lesion Model of Temporal Lobe Epilepsy.

    PubMed

    Gorantla, Vasavi R; Sirigiri, Amulya; Volkova, Yulia A; Millis, Richard M

    2016-01-01

    Temporal lobe epilepsy (TLE) is a common neurological disease and antiseizure medication is often inadequate for preventing apoptotic cell death. Aerobic swimming exercise (EX) augments neurogenesis in rats when initiated immediately in the postictal period. This study tests the hypothesis that aerobic exercise also augments neurogenesis over the long term. Male Wistar rats (age of 4 months) were subjected to chemical lesioning using KA and to an EX intervention consisting of a 30 d period of daily swimming for 15 min, in one experiment immediately after KA lesioning (immediate exposure) and in a second experiment after a 60 d period of normal activity (delayed exposure). Morphometric counting of neuron numbers (NN) and dendritic branch points and intersections (DDBPI) was performed in the CA1, CA3, and dentate regions of hippocampus, in basolateral nucleus of amygdala, and in several areas of motor cortex. EX increased NN and DDBPI in the normal control and the KA-lesioned rats in all four limbic and motor cortex areas studied, after both immediate and 60 d delayed exposures to exercise. These findings suggest that, after temporal lobe epileptic seizures in rats, swimming exercise may improve neural plasticity in areas of the brain involved with emotional regulation and motor coordination, even if the exercise treatment is delayed.

  6. 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

  7. Real-time classification of activated brain areas for fMRI-based human-brain-interfaces

    NASA Astrophysics Data System (ADS)

    Moench, Tobias; Hollmann, Maurice; Grzeschik, Ramona; Mueller, Charles; Luetzkendorf, Ralf; Baecke, Sebastian; Luchtmann, Michael; Wagegg, Daniela; Bernarding, Johannes

    2008-03-01

    Functional MR imaging (fMRI) enables to detect different activated brain areas according to the performed tasks. However, data are usually evaluated after the experiment, which prohibits intra-experiment optimization or more sophisticated applications such as biofeedback experiments. Using a human-brain-interface (HBI), subjects are able to communicate with external programs, e.g. to navigate through virtual scenes, or to experience and modify their own brain activation. These applications require the real-time analysis and classification of activated brain areas. Our paper presents first results of different strategies for real-time pattern analysis and classification realized within a flexible experiment control system that enables the volunteers to move through a 3D virtual scene in real-time using finger tapping tasks, and alternatively only thought-based tasks.

  8. Within brain area tractography suggests local modularity using high resolution connectomics

    PubMed Central

    Taylor, Peter N.; Wang, Yujiang; Kaiser, Marcus

    2017-01-01

    Previous structural brain connectivity studies have mainly focussed on the macroscopic scale of around 1,000 or fewer brain areas (network nodes). However, it has recently been demonstrated that high resolution structural connectomes of around 50,000 nodes can be generated reproducibly. In this study, we infer high resolution brain connectivity matrices using diffusion imaging data from the Human Connectome Project. With such high resolution we are able to analyse networks within brain areas in a single subject. We show that the global network has a scale invariant topological organisation, which means there is a hierarchical organisation of the modular architecture. Specifically, modules within brain areas are spatially localised. We find that long range connections terminate between specific modules, whilst short range connections via highly curved association fibers terminate within modules. We suggest that spatial locations of white matter modules overlap with cytoarchitecturally distinct grey matter areas and may serve as the structural basis for function specialisation within brain areas. Future studies might elucidate how brain diseases change this modular architecture within brain areas. PMID:28054634

  9. Communication between Brain Areas Based on Nested Oscillations

    PubMed Central

    Kastner, Sabine

    2017-01-01

    Abstract Unraveling how brain regions communicate is crucial for understanding how the brain processes external and internal information. Neuronal oscillations within and across brain regions have been proposed to play a crucial role in this process. Two main hypotheses have been suggested for routing of information based on oscillations, namely communication through coherence and gating by inhibition. Here, we propose a framework unifying these two hypotheses that is based on recent empirical findings. We discuss a theory in which communication between two regions is established by phase synchronization of oscillations at lower frequencies (<25 Hz), which serve as temporal reference frame for information carried by high-frequency activity (>40 Hz). Our framework, consistent with numerous recent empirical findings, posits that cross-frequency interactions are essential for understanding how large-scale cognitive and perceptual networks operate. PMID:28374013

  10. Neuroimaging of frontal-limbic dysfunction in schizophrenia and epilepsy-related psychosis: toward a convergent neurobiology.

    PubMed

    Butler, Tracy; Weisholtz, Daniel; Isenberg, Nancy; Harding, Elizabeth; Epstein, Jane; Stern, Emily; Silbersweig, David

    2012-02-01

    Psychosis is a devastating, prevalent condition considered to involve dysfunction of frontal and medial temporal limbic brain regions as key nodes in distributed brain networks involved in emotional regulation. The psychoses of epilepsy represent an important, though understudied, model relevant to understanding the pathophysiology of psychosis in general. In this review, we (1) discuss the classification of epilepsy-related psychoses and relevant neuroimaging and other studies; (2) review structural and functional neuroimaging studies of schizophrenia focusing on evidence of frontal-limbic dysfunction; (3) report our laboratory's PET, fMRI, and electrophysiological findings; (4) describe a theoretical framework in which frontal hypoactivity and intermittent medial temporal hyperactivity play a critical role in the etiopathology of psychosis both associated and unassociated with epilepsy; and (5) suggest avenues for future research. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Corticotropin-releasing hormone activates ERK1/2 MAPK in specific brain areas.

    PubMed

    Refojo, Damián; Echenique, Carlos; Müller, Marianne B; Reul, Johannes M H M; Deussing, Jan M; Wurst, Wolfgang; Sillaber, Inge; Paez-Pereda, Marcelo; Holsboer, Florian; Arzt, Eduardo

    2005-04-26

    Corticotropin-releasing hormone (CRH) coordinates hormonal and behavioral responses to stress. The mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2) mediates several functions in different forebrain structures and recently has been implicated in CRH signaling in cultured cells. To study in vivo CRH-mediated activation of central ERK1/2, we investigated the expression pattern of the phosphorylated ERK1/2(p-ERK1/2) in the mouse brain after intracerebroventricular CRH injections. As shown by immunohistochemistry and confocal microscopy analysis, CRH administration increased p-ERK1/2 levels specifically in the CA3 and CA1 hippocampal subfields and basolateral complex of the amygdala, both structures related to external environmental information processing and behavioral aspects of stress. Other regions such as hypothalamic nuclei and the central nucleus of the amygdala, also related to central CRH system but involved in the processing of the ascending visceral information and neuroendocrine-autonomic response to stress, did not show CRH-mediated ERK1/2 activation. To dissect the involvement of CRH receptor 1 (CRHR1) and CRHR2, we used conditional knockout mice in which Crhr1 is inactivated in the anterior forebrain and limbic structures. The conditional genetic ablation of Crhr1 inhibited the p-ERK1/2 increase, underlining the involvement of CRHR1 in the CRH-mediated activation. These findings underscore the fact that CRH activates p-ERK1/2 through CRHR1 only in selected brain regions, pointing to a specific role of this pathway in mediating behavioral adaptation to stress.

  12. [Following sensory neuropathy, anti-Hu antibody-positive paraneoplastic neurological syndrome presenting with limbic encephalitis occurs after complete remission].

    PubMed

    Fukami, Yuki; Umemura, Toshitaka; Shimono, Tetufumi; Yokoi, Takamasa; Kamijo, Mikiko; Sakakibara, Toshimasa

    2013-01-01

    Paraneoplastic limbic encephalitis is a rare neurological disorder that frequently precedes the detection of malignancy. We report the case of a 68-year-old male with small-cell lung cancer who developed paraneoplastic limbic encephalitis associated with presence of the anti-Hu antibody, after achieving complete remission of the tumor by chemotherapy. The patient visited our hospital because of progressive sensory disturbance of the distal extremities at 65 years of age. Though paraneoplastic sensory neuropathy was suspected, we could not find any tumor and he did not improve with steroids or immunoglobulin therapy. Chest computed tomography (CT) revealed large mediastinal lymphadenopathy. He was subsequently diagnosed with small cell lung cancer at one year and three months after the neurological symptoms occurred. As his serum analysis was positive for the anti-Hu antibody, we diagnosed paraneoplastic sensory neuropathy. The lung cancer disappeared with chemotherapy, but he had developed short-term memory loss six months later. Brain fluid attenuated inversion recovery (FLAIR) imaging showed an abnormal high-intensity lesion in the left medial temporal lobe including the hippocampus. We therefore made the diagnosis of paraneoplastic limbic encephalitis following subacute sensory neuropathy associated with the anti-Hu antibody. To our knowledge, this is the first report of a patient presenting with paraneoplastic neurological syndrome in which limbic encephalitis developed after tumor disappearance. So we must recognize the possibility of neurological symptoms occurring during remission. As the mechanism of pathogenesis, delayed neuronal cell damage due to immune responses against the tumor is implicated.

  13. Environmental enrichment delays limbic epileptogenesis and restricts pathologic synaptic plasticity.

    PubMed

    Yang, Meng; Ozturk, Ezgi; Salzberg, Michael R; Rees, Sandra; Morris, Margaret; O'Brien, Terence J; Jones, Nigel C

    2016-03-01

    Environmental exposures impart powerful effects on vulnerability to many brain diseases, including epilepsy. Mesial temporal lobe epilepsy (MTLE) is a common form of epilepsy, and it is often accompanied by neuropsychiatric comorbidities. This study tests the hypothesis that environmental enrichment (EE) confers antiepileptogenic, psychoprotective, and neuroprotective effects in the amygdala kindling model of MTLE, and explores potential neurobiologic mechanisms. At weaning, male Wistar rats were allocated into either EE (large cages containing running wheels and toys; n = 43) or standard housing (SH; standard laboratory cages; n = 39) conditions. At P56, a bipolar electrode was implanted into the left amygdala, and rats underwent rapid amygdala kindling until experiencing five class V seizures (Racine scale, fully kindled). The elevated plus maze was used to assess anxiety. Postmortem histologic and molecular analyses investigated potential biologic mediators of effects. EE significantly delayed kindling epileptogenesis, with EE rats requiring a significantly greater number of kindling stimulations to reach a fully kindled state compared to SH rats (p < 0.05). EE and kindling both reduced anxiety (p < 0.05). Timm's staining revealed significant reductions in aberrant mossy fiber sprouting in EE rats (p < 0.05), and these effects of EE were accompanied by reduced expression of TrkB and CRH genes. We identify beneficial effects of EE on vulnerability to limbic epileptogenesis and anxiety, and identify reduced pathologic neuroplasticity and plasticity-related gene expression as potential underlying mechanisms. Enhanced environmental stimulation represents a potential antiepileptogenic strategy that might also mitigate the common psychiatric comorbidities of MTLE. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  14. 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

  15. Childhood maltreatment, altered limbic neurobiology, and substance use relapse severity via trauma-specific reductions in limbic gray matter volume.

    PubMed

    Van Dam, Nicholas T; Rando, Kenneth; Potenza, Marc N; Tuit, Keri; Sinha, Rajita

    2014-08-01

    Substance use disorders (SUDs) are among the most common sequelae of childhood maltreatment, yet the independent contributions of SUDs and childhood maltreatment to neurobiological changes and the effect of the latter on relapse risk (a critical variable in addiction treatment) are relatively unknown. To identify structural neural characteristics independently associated with childhood maltreatment (CM; a common type of childhood adversity), comparing a sample with SUD with a demographically comparable control sample, and to examine the relationship between CM-related structural brain changes and subsequent relapse. Structural magnetic resonance imaging study comparing 79 treatment-engaged participants with SUD in acute remission in inpatient treatment at a community mental health center vs 98 healthy control participants at an outpatient research center at an academic medical center. Both groups included individuals with a range of CM experiences. Participants with SUD were followed up prospectively for 90 days to assess relapse and relapse severity. Standard 12-step, recovery-based, inpatient addiction treatment for all participants with SUD. Gray matter volume (GMV), subsequent substance use relapse, days to relapse, and severity of relapse. Controlling for SUD and psychiatric comorbidity, CM (dichotomously classified) was uniquely associated with lower GMV across all participants in the left hippocampus (cornu ammonis 1-3, dentate gyrus), parahippocampus (presubiculum, parasubiculum, prosubiculum, subiculum, and entorhinal cortex), and anterior fusiform gyrus (corrected P < .05; uncorrected P = .001). Among the sample with SUD, CM prospectively predicted a shorter relapse to use of any drug (P = .048), while CM-related GMV reductions predicted severity of substance use relapse (P = .04). Findings indicate that CM was related to decreased GMV in limbic regions, which in turn predicted increased risk of relapse in SUD. These results suggest that

  16. Childhood Maltreatment, Altered Limbic Neurobiology, and Substance Use Relapse Severity via Trauma-Specific Reductions in Limbic Gray Matter Volume

    PubMed Central

    Van Dam, Nicholas T.; Rando, Kenneth; Potenza, Marc N.; Tuit, Keri; Sinha, Rajita

    2015-01-01

    IMPORTANCE Substance use disorders (SUDs) are among the most common sequelae of childhood maltreatment, yet the independent contributions of SUDs and childhood maltreatment to neurobiological changes and the effect of the latter on relapse risk (a critical variable in addiction treatment) are relatively unknown. OBJECTIVES To identify structural neural characteristics independently associated with childhood maltreatment (CM; a common type of childhood adversity), comparing a sample with SUD with a demographically comparable control sample, and to examine the relationship between CM-related structural brain changes and subsequent relapse. DESIGN, SETTING, AND PARTICIPANTS Structural magnetic resonance imaging study comparing 79 treatment-engaged participants with SUD in acute remission in inpatient treatment at a community mental health center vs 98 healthy control participants at an outpatient research center at an academic medical center. Both groups included individuals with a range of CM experiences. Participants with SUD were followed up prospectively for 90 days to assess relapse and relapse severity. INTERVENTION Standard 12-step, recovery-based, inpatient addiction treatment for all participants with SUD. MAIN OUTCOMES AND MEASURES Gray matter volume (GMV), subsequent substance use relapse, days to relapse, and severity of relapse. RESULTS Controlling for SUD and psychiatric comorbidity, CM (dichotomously classified) was uniquely associated with lower GMV across all participants in the left hippocampus (cornu ammonis 1-3, dentate gyrus), parahippocampus (presubiculum, parasubiculum, prosubiculum, subiculum, and entorhinal cortex), and anterior fusiform gyrus (corrected P < .05; uncorrected P = .001). Among the sample with SUD, CM prospectively predicted a shorter relapse to use of any drug (P = .048), while CM-related GMV reductions predicted severity of substance use relapse (P = .04). CONCLUSIONS AND RELEVANCE Findings indicate that CM was related to

  17. 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.

  18. Limbic Tract Integrity Contributes to Pattern Separation Performance Across the Lifespan.

    PubMed

    Bennett, Ilana J; Huffman, Derek J; Stark, Craig E L

    2015-09-01

    Accurate memory for discrete events is thought to rely on pattern separation to orthogonalize the representations of similar events. Previously, we reported that a behavioral index of pattern separation was correlated with activity in the hippocampus (dentate gyrus, CA3) and with integrity of the perforant path, which provides input to the hippocampus. If the hippocampus operates as part of a broader neural network, however, pattern separation would likely also relate to integrity of limbic tracts (fornix, cingulum bundle, and uncinate fasciculus) that connect the hippocampus to distributed brain regions. In this study, healthy adults (20-89 years) underwent diffusion tensor imaging and completed the Behavioral Pattern Separation Task-Object Version (BPS-O) and Rey Auditory Verbal Learning Test (RAVLT). After controlling for global effects of brain aging, exploratory skeleton-wise and targeted tractography analyses revealed that fornix integrity (fractional anisotropy, mean diffusivity, and radial diffusivity; but not mode) was significantly related to pattern separation (measured using BPS-O and RAVLT tasks), but not to recognition memory. These data suggest that hippocampal disconnection, via individual- and age-related differences in limbic tract integrity, contributes to pattern separation performance. Extending our earlier work, these results also support the notion that pattern separation relies on broad neural networks interconnecting the hippocampus.

  19. Limbic Tract Integrity Contributes to Pattern Separation Performance Across the Lifespan

    PubMed Central

    Bennett, Ilana J.; Huffman, Derek J.; Stark, Craig E.L.

    2015-01-01

    Accurate memory for discrete events is thought to rely on pattern separation to orthogonalize the representations of similar events. Previously, we reported that a behavioral index of pattern separation was correlated with activity in the hippocampus (dentate gyrus, CA3) and with integrity of the perforant path, which provides input to the hippocampus. If the hippocampus operates as part of a broader neural network, however, pattern separation would likely also relate to integrity of limbic tracts (fornix, cingulum bundle, and uncinate fasciculus) that connect the hippocampus to distributed brain regions. In this study, healthy adults (20–89 years) underwent diffusion tensor imaging and completed the Behavioral Pattern Separation Task-Object Version (BPS-O) and Rey Auditory Verbal Learning Test (RAVLT). After controlling for global effects of brain aging, exploratory skeleton-wise and targeted tractography analyses revealed that fornix integrity (fractional anisotropy, mean diffusivity, and radial diffusivity; but not mode) was significantly related to pattern separation (measured using BPS-O and RAVLT tasks), but not to recognition memory. These data suggest that hippocampal disconnection, via individual- and age-related differences in limbic tract integrity, contributes to pattern separation performance. Extending our earlier work, these results also support the notion that pattern separation relies on broad neural networks interconnecting the hippocampus. PMID:24825784

  20. Magnesium, aluminum and lead in various brain areas

    SciTech Connect

    Zumkley, H.; Bertram, H.P.; Brandt, M.; Roedig, M.; Spieker, C.

    1986-01-01

    Whereas the lead concentrations were increased in brain tissue of patients with chronic alcoholism, the aluminum concentrations remained within the normal range. The magnesium concentrations were found decreased in patients with chronic alcoholism compared to normal controls. The sources for the elevated lead levels seem to be the increased intake of alcohol. The decreased magnesium levels are probably caused by an increased loss of magnesium with the urine, malnutrition, malabsorption, hormonal factors and drugs. Various neurological disorders which often accompanied chronic alcoholism may be caused or aggravated by lead encephalopathy and hypomagnesemia. Therapeutical implications may be the early substitution of magnesium deficiency in chronic alcoholism. 10 references, 5 figures.

  1. Areas of Brain Damage Underlying Increased Reports of Behavioral Disinhibition.

    PubMed

    Knutson, Kristine M; Dal Monte, Olga; Schintu, Selene; Wassermann, Eric M; Raymont, Vanessa; Grafman, Jordan; Krueger, Frank

    2015-01-01

    Disinhibition, the inability to inhibit inappropriate behavior, is seen in frontal-temporal degeneration, Alzheimer's disease, and stroke. Behavioral disinhibition leads to social and emotional impairments, including impulsive behavior and disregard for social conventions. The authors investigated the effects of lesions on behavioral disinhibition measured by the Neuropsychiatric Inventory in 177 veterans with traumatic brain injuries. The authors performed voxel-based lesion-symptom mapping using MEDx. Damage in the frontal and temporal lobes, gyrus rectus, and insula was associated with greater behavioral disinhibition, providing further evidence of the frontal lobe's involvement in behavioral inhibition and suggesting that these regions are necessary to inhibit improper behavior.

  2. [The language area of the brain: a functional reassessment].

    PubMed

    Ardila, Alfredo; Bernal, Byron; Rosselli, Monica

    2016-02-01

    Introduccion. Hacia finales del siglo XIX y comienzos del siglo XX, y basandose en observaciones clinicas, se propuso que existe un 'area del lenguaje' en el cerebro que corresponde, en general, a la region perisilviana del hemisferio izquierdo. Tal idea ha continuado existiendo desde entonces. Objetivo. Partiendo de los estudios contemporaneos de imagenes cerebrales, reanalizar la localizacion y extension del area del lenguaje con relacion a las diferentes areas de Brodmann. Materiales y metodos. Utilizando la metodologia conocida como metaanalytic connectivity modeling, se revisan varios estudios metaanaliticos en los cuales se analizan las imagenes de resonancia magnetica funcional durante la realizacion de tareas linguisticas. Resultados. Se encontro que existen dos sistemas linguisticos diferentes en el cerebro: un sistema lexico/semantico, relacionado con el area de Wernicke, y que incluye un area de Wernicke central (reconocimiento de palabras) y un area de Wernicke extendida (asociaciones linguisticas); y un sistema gramatical, dependiente del complejo de Broca (produccion del lenguaje y gramatica), en el lobulo frontal, y que se extiende subcorticalmente. Se propone tambien que la insula desempeña un papel de coordinacion de estos dos sistemas linguisticos cerebrales. Conclusion. Los estudios contemporaneos de neuroimagen sugieren que el area del lenguaje en el cerebro es notoriamente mas amplia de lo que se supuso hace un siglo basandose en observaciones clinicas. Tal como se consideraba durante el siglo XIX, la insula parece desempeñar un papel critico en el lenguaje.

  3. Mapping orbitofrontal-limbic maturation in non-human primates: A longitudinal magnetic resonance imaging study.

    PubMed

    Uematsu, Akiko; Hata, Junichi; Komaki, Yuji; Seki, Fumiko; Yamada, Chihoko; Okahara, Norio; Kurotaki, Yoko; Sasaki, Erika; Okano, Hideyuki

    2017-09-18

    Brain development involves spatiotemporally complex microstructural changes. A number of neuropsychiatric disorders are linked to the neural processes of development and aging. Thus, it is important to understanding the typical developmental patterns of various brain structures, which will help to define critical periods of vulnerability for neural maturation, as well as anatomical mechanisms of brain structure-related neuropathology. In this study, we used magnetic resonance imaging to assess development of the orbitofrontal cortex, cingulate cortex, amygdala, and hippocampus in a non-human primate species, the common marmoset (Callithrix jacchus). We collected a total of 114 T2-weighted and 91 diffusion-weighted scans from 23 animals from infancy to early adulthood. Quantitative and qualitative evaluation of age-related brain growth patterns showed non-linear structural developmental changes in all measured brain regions, consistent with reported human data. Overall, robust volumetric growth was observed from 1 to 3 months of age (from infancy to the early juvenile period). This rapid brain growth was associated with the largest decrease in mean, axial, and radial diffusivities of diffusion tensor imaging in all brain regions, suggesting an increase in the number and size of cells, dendrites, and spines during this period. After this developmental period, the volume of various brain regions steadily increased until adolescence (7-13 months of age, depending on the region). Further, structural connectivity derived from tractography data in various brain regions continuously changed from infancy to adolescence, suggesting that the increase in brain volume was related to continued axonal myelination during adolescence. Thereafter, the volume of the cortical regions decreased considerably, while there was no change in subcortical regions. Familial factors, rather than sex, contributed the development of the front-limbic brain regions. Overall, this study provides

  4. Preservation of mitochondrial functional integrity in mitochondria isolated from small cryopreserved mouse brain areas.

    PubMed

    Valenti, Daniela; de Bari, Lidia; De Filippis, Bianca; Ricceri, Laura; Vacca, Rosa Anna

    2014-01-01

    Studies of mitochondrial bioenergetics in brain pathophysiology are often precluded by the need to isolate mitochondria immediately after tissue dissection from a large number of brain biopsies for comparative studies. Here we present a procedure of cryopreservation of small brain areas from which mitochondrial enriched fractions (crude mitochondria) with high oxidative phosphorylation efficiency can be isolated. Small mouse brain areas were frozen and stored in a solution containing glycerol as cryoprotectant. Crude mitochondria were isolated by differential centrifugation from both cryopreserved and freshly explanted brain samples and were compared with respect to their ability to generate membrane potential and produce ATP. Intactness of outer and inner mitochondrial membranes was verified by polarographic ascorbate and cytochrome c tests and spectrophotometric assay of citrate synthase activity. Preservation of structural integrity and oxidative phosphorylation efficiency was successfully obtained in crude mitochondria isolated from different areas of cryopreserved mouse brain samples. Long-term cryopreservation of small brain areas from which intact and phosphorylating mitochondria can be isolated for the study of mitochondrial bioenergetics will significantly expand the study of mitochondrial defects in neurological pathologies, allowing large comparative studies and favoring interlaboratory and interdisciplinary analyses.

  5. Area V5—a microcosm of the visual brain

    PubMed Central

    Zeki, Semir

    2015-01-01

    Area V5 of the visual brain, first identified anatomically in 1969 as a separate visual area, is critical for the perception of visual motion. As one of the most intensively studied parts of the visual brain, it has yielded many insights into how the visual brain operates. Among these are: the diversity of signals that determine the functional capacities of a visual area; the relationship between single cell activity in a specialized visual area and perception of, and preference for, attributes of a visual stimulus; the multiple asynchronous inputs into, and outputs from, an area as well as the multiple operations that it undertakes asynchronously; the relationship between activity at given, specialized, areas of the visual brain and conscious awareness; and the mechanisms used to “bind” signals from one area with those from another, with a different specialization, to give us our unitary perception of the visual world. Hence V5 is, in a sense, a microcosm of the visual world and its study gives important insights into how the whole visual brain is organized—anatomically, functionally and perceptually. PMID:25883556

  6. Methylphenidate reduces functional connectivity of nucleus accumbens in brain reward circuit.

    PubMed

    Ramaekers, J G; Evers, E A; Theunissen, E L; Kuypers, K P C; Goulas, A; Stiers, P

    2013-09-01

    Release of dopamine in the nucleus accumbens (NAcc) is essential for acute drug reward. The present study was designed to trace the reinforcing effect of dopamine release by measuring the functional connectivity (FC) between the NAcc and brain regions involved in a limbic cortical-subcortical circuit during a dopaminergic challenge. Twenty healthy volunteers received single doses of methylphenidate (40 mg) and placebo on separate test days according to a double-blind, cross-over study design. Resting state functional magnetic resonance imaging (fMRI) was measured between 1.5 and 2 h postdosing. FC between regions of interest (ROI) in the NAcc, the medial dorsal nucleus (MDN) of the thalamus and remote areas within the limbic circuit was explored. Methylphenidate significantly reduced FC between the NAcc and the basal ganglia (i.e., subthalamic nucleus and ventral pallidum (VP)), relative to placebo. Methylphenidate also decreased FC between the NAcc and the medial prefrontal cortex (mPFC) as well as the temporal cortex. Methylphenidate did not affect FC between MDN and the limbic circuit. It is concluded that methylphenidate directly affects the limbic reward circuit. Drug-induced changes in FC of the NAcc may serve as a useful marker of drug activity in in the brain reward circuit.

  7. The time-course of cortico-limbic neural responses to air hunger.

    PubMed

    Binks, Andrew P; Evans, Karleyton C; Reed, Jeffrey D; Moosavi, Shakeeb H; Banzett, Robert B

    2014-12-01

    Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (∼ 45 mm Hg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (V(T)) was alternated every 90 s between high VT (0.96 ± 0.23 L) that provided respiratory comfort (12 ± 6% full scale) and low V(T) (0.48 ± 0.08 L) which evoked air hunger (56 ± 11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak <30s and (2) slow, BOLD signal peak >40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research.

  8. One century of brain mapping using Brodmann areas.

    PubMed

    Strotzer, Michael

    2009-08-01

    100 years after their publication, Brodmann's maps of the cerebral cortex are universally used to locate neuropsychological functions. On the occasion of this jubilee the life and work of Korbinian Brodmann are reported. The core functions of each single Brodmann area are described and Brodmann's views on neuropsychological processes are depicted.

  9. [OCD: when limbic systems start looping...].

    PubMed

    Flores Alves dos Santos, João; Mallet, Luc

    2013-05-01

    Obsessive Compulsive Disorder (OCD) is a disease that affects 2-3% of the population with high comorbidity and a negative impact on the person overall functioning. About 30% of patients have severe and persistent symptoms despite the combination of pharmacological and psychotherapeutic treatments. In these cases, deep brain stimulation (DBS) of the subthalamic nucleus allows both the reduction of symptoms severity and the improvement in overall functioning. A clinical case is presented by integrating the latest data research to show not only the result of DBS therapy but also its contribution to a better understanding of the pathophysiology of OCD.

  10. Electrical stimulation of a small brain area reversibly disrupts consciousness.

    PubMed

    Koubeissi, Mohamad Z; Bartolomei, Fabrice; Beltagy, Abdelrahman; Picard, Fabienne

    2014-08-01

    The neural mechanisms that underlie consciousness are not fully understood. We describe a region in the human brain where electrical stimulation reproducibly disrupted consciousness. A 54-year-old woman with intractable epilepsy underwent depth electrode implantation and electrical stimulation mapping. The electrode whose stimulation disrupted consciousness was between the left claustrum and anterior-dorsal insula. Stimulation of electrodes within 5mm did not affect consciousness. We studied the interdependencies among depth recording signals as a function of time by nonlinear regression analysis (h(2) coefficient) during stimulations that altered consciousness and stimulations of the same electrode at lower current intensities that were asymptomatic. Stimulation of the claustral electrode reproducibly resulted in a complete arrest of volitional behavior, unresponsiveness, and amnesia without negative motor symptoms or mere aphasia. The disruption of consciousness did not outlast the stimulation and occurred without any epileptiform discharges. We found a significant increase in correlation for interactions affecting medial parietal and posterior frontal channels during stimulations that disrupted consciousness compared with those that did not. Our findings suggest that the left claustrum/anterior insula is an important part of a network that subserves consciousness and that disruption of consciousness is related to increased EEG signal synchrony within frontal-parietal networks. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Specific EEG frequencies at specific brain areas and performance.

    PubMed

    Fernández, T; Harmony, T; Silva-Pereyra, J; Fernández-Bouzas, A; Gersenowies, J; Galán, L; Carbonell, F; Marosi, E; Otero, G; Valdés, S I

    2000-08-21

    In this study it was shown that in adults, the frequency characteristics of EEG preceding stimuli that were followed by incorrect responses were different from the characteristics of EEG preceding stimuli that were followed by correct responses. In the recording during three different tasks that explore different neuronal networks, higher values of current preceding incorrect performance in those areas directly related to the task were found in frequencies within the delta (1.56 and 3.12 Hz) and beta bands (13.26, 14.04, 14.82, 15.6, 17.16 and 17.94 Hz), suggesting that these frequencies signal inhibition. Frequencies within the alpha band (9.36 and 12.48 Hz) showed greater energy preceding correct responses in task-specific areas, supporting previous results observed in children.

  12. Functional connectivity between brain areas estimated by analysis of gamma waves.

    PubMed

    Kheiri, Farshad; Bragin, Anatol; Engel, Jerome

    2013-04-15

    The goal of this study is to investigate functional connectivity between different brain regions by analyzing the temporal relationship of the maxima of gamma waves recorded in multiple brain areas. Local field potentials were recorded from motor cortex, hippocampus, entorhinal cortex and piriform cortex of rats. Gamma activity was filtered and separated into two bands; high (65-90Hz) and low (30-55Hz) gamma. Maxima for gamma activity waves were detected and functional connectivity between different brain regions was determined using Shannon entropy for perievent histograms for each pair channels. Significant Shannon entropy values were reported as connectivity factors. We defined a connectivity matrix based the connectivity factors between different regions. We found that maxima of low and high frequency gamma occur in strong temporal relationship between some brain areas, indicating the existence of functional connections between these areas. The spatial pattern of functional connections between brain areas was different for slow wave sleep and waking states. However for each behavioral state in the same animal the pattern of functional connections was stable over time within 30min of continuous analysis and over a 5 day period. With the same electrode montage the pattern of functional connectivity varied from one subject to another. Analysis of the temporal relationship of maxima of gamma waves between various brain areas could be a useful tool for investigation of functional connections between these brain areas. This approach could be applied for analysis of functional alterations occurring in these connections during different behavioral tasks and during processes related to learning and memory. The specificity in the connectivity pattern from one subject to another can be explained by the existence of unique functional networks for each subject. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis.

    PubMed

    Vincent, Angela; Buckley, Camilla; Schott, Jonathan M; Baker, Ian; Dewar, Bonnie-Kate; Detert, Niels; Clover, Linda; Parkinson, Abigail; Bien, Christian G; Omer, Salah; Lang, Bethan; Rossor, Martin N; Palace, Jackie

    2004-03-01

    Patients presenting with subacute amnesia are frequently seen in acute neurological practice. Amongst the differential diagnoses, herpes simplex encephalitis, Korsakoff's syndrome and limbic encephalitis should be considered. Limbic encephalitis is typically a paraneoplastic syndrome with a poor prognosis; thus, identifying those patients with potentially reversible symptoms is important. Voltage-gated potassium channel antibodies (VGKC-Ab) have recently been reported in three cases of reversible limbic encephalitis. Here we review the clinical, immunological and neuropsychological features of 10 patients (nine male, one female; age range 44-79 years), eight of whom were identified in two centres over a period of 15 months. The patients presented with 1-52 week histories of memory loss, confusion and seizures. Low plasma sodium concentrations, initially resistant to treatment, were present in eight out of 10. Brain MRI at onset showed signal change in the medial temporal lobes in eight out of 10 cases. Paraneoplastic antibodies were negative, but VGKC-Ab ranged from 450 to 5128 pM (neurological and healthy controls <100 pM). CSF oligoclonal bands were found in only one, but bands matched with those in the serum were found in six other patients. VGKC-Abs in the CSF, tested in five individuals, varied between <1 and 10% of serum values. Only one patient had neuromyotonia, which was excluded by electromyography in seven of the others. Formal neuropsychology testing showed severe and global impairment of memory, with sparing of general intellect in all but two patients, and of nominal functions in all but one. Variable regimes of steroids, plasma exchange and intravenous immunoglobulin were associated with variable falls in serum VGKC-Abs, to values between 2 and 88% of the initial values, together with marked improvement of neuropsychological functioning in six patients, slight improvement in three and none in one. The improvement in neuropsychological functioning in

  14. [Brodmann Areas 17, 18, and 19 in the Human Brain: An Overview].

    PubMed

    Kawachi, Juro

    2017-04-01

    Brodmann areas 17, 18, and 19 in the human brain are visual cortices of the occipital lobe. Each area has its own retinotopic representations, particulary area 19, which has many small retinotopic areas representing half or all of the contralateral visual field, several functional areas, and nine cytoarchitectonic areas. Several fasciculi are known as occipital fiber connections, but their precise endpoints are not clear. Lesions in the visual cortices cause several visual disorders including visual field defect, visual hallucinations, metamorphopsia, and different kinds of visual agnosia.

  15. GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

    PubMed Central

    Avoli, Massimo; de Curtis, Marco

    2016-01-01

    GABA is the main inhibitory neurotransmitter in the adult forebrain, where it activates ionotropic type A and metabotropic type B receptors. Early studies have shown that GABAA receptor-mediated inhibition controls neuronal excitability and thus the occurrence of seizures. However, more complex, and at times unexpected, mechanisms of GABAergic signaling have been identified during epileptiform discharges over the last few years. Here, we will review experimental data that point at the paradoxical role played by GABAA receptor-mediated mechanisms in synchronizing neuronal networks, and in particular those of limbic structures such as the hippocampus, the entorhinal and perirhinal cortices, or the amygdala. After having summarized the fundamental characteristics of GABAA receptor-mediated mechanisms, we will analyze their role in the generation of network oscillations and their contribution to epileptiform synchronization. Whether and how GABAA receptors influence the interaction between limbic networks leading to ictogenesis will be also reviewed. Finally, we will consider the role of altered inhibition in the human epileptic brain along with the ability of GABAA receptor-mediated conductances to generate synchronous depolarizing events that may lead to ictogenesis in human epileptic disorders as well. PMID:21802488

  16. 5HTTLPR polymorphism and enlargement of the pulvinar: unlocking the backdoor to the limbic system.

    PubMed

    Young, Keith A; Holcomb, Leigh A; Bonkale, Willy L; Hicks, Paul B; Yazdani, Umar; German, Dwight C

    2007-03-15

    The 5HTTLPR genetic variant of the serotonin transporter (SERT), which consists of a long (SERT-l) and short (SERT-s) allele, has emerged as a major factor influencing emotional behavior and brain anatomy. The pulvinar nucleus of the thalamus projects to important limbic nuclei including the amygdala and cingulate cortex, is involved in the processing of stimuli with emotional content, and contains an abundance of SERT. Stereological methods were used to measure pulvinar neuron number in postmortem tissue from major depressive disorder (n = 11), bipolar disorder (n = 11), schizophrenia (n = 12), and control (n = 15) specimens from the Stanley Foundation Neuropathology Consortium. The effect of SERT genotype on pulvinar volume and neuron number was investigated by using analysis of covariance. Analysis of covariance with diagnosis, SERT genotype, age, hemisphere, postmortem interval, and time-in-formalin covariates identified a 20% increase in pulvinar neuron number and volume in SERT-ss subjects. The elevated number of pulvinar neurons in subjects with a SERT-ss genotype may serve to enhance subcortical input of emotionally relevant stimuli to the limbic system, providing a mechanism for the 5HTTLPR genetic variant to affect predisposition to conditions such as major depression.

  17. 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.

  18. 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

  19. Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons.

    PubMed

    Tan, Guo-He; Liu, Yuan-Yuan; Hu, Xiao-Ling; Yin, Dong-Min; Mei, Lin; Xiong, Zhi-Qi

    2011-12-11

    Epilepsy is a common and refractory neurological disorder, but the neuronal regulatory mechanisms of epileptogenesis remain largely unclear. Activity-dependent transcription of genes for neurotrophins such as brain-derived neurotrophic factor (BDNF) has been shown to promote epileptogenesis; however, little is known about factors that may act as intrinsic, homeostatic or counterbalancing mechanisms. Using rodent models, here we show that limbic seizure activity upregulated NRG1-ErbB4 signaling and that epileptogenesis was inhibited by infusing NRG1 intracerebrally but exacerbated by neutralizing endogenous NRG1 with soluble ErbB4 extracellular domain, by inhibiting ErbB4 activation or by deleting the Erbb4 gene. Furthermore, specific depletion of ErbB4 in parvalbumin-expressing interneurons abolished NRG1-mediated inhibition of epileptogenesis and promoted kindling progression, resulting in increased spontaneous seizures and exuberant mossy fiber sprouting. In contrast, depleting ErbB4 in CaMKIIα-positive pyramidal neurons had no effect. Thus, NRG1-induced activation of ErbB4 in parvalbumin-expressing inhibitory interneurons may serve as a critical endogenous negative-feedback mechanism to suppress limbic epileptogenesis.

  20. Voltage-gated potassium channel antibody paraneoplastic limbic encephalitis associated with acute myeloid leukemia.

    PubMed

    Alcantara, Marion; Bennani, Omar; Verdure, Pierre; Leprêtre, Stéphane; Tilly, Hervé; Jardin, Fabrice

    2013-05-01

    Among paraneoplastic syndromes (PNS) associated with malignant hemopathies, there are few reports of PNS of the central nervous system and most of them are associated with lymphomas. Limbic encephalitis is a rare neurological syndrome classically diagnosed in the context of PNS. We report the case of a 81-year-old man who presented with a relapsed acute myeloid leukemia (AML) with minimal maturation. He was admitted for confusion with unfavorable evolution as he presented a rapidly progressive dementia resulting in death. A brain magnetic resonance imaging, performed 2 months after the onset, was considered normal. An electroencephalogram showed non-specific bilateral slow waves. We received the results of the blood screening of neuronal autoanti-bodies after the patient's death and detected the presence of anti-voltage-gated potassium channel (VGKC) antibodies at 102 pmol/l (normal at <30 pmol/l). Other etiologic studies, including the screening for another cause of rapidly progressive dementia, were negative. To our knowledge, this is the first case of anti-VGKC paraneoplastic limbic encephalitis related to AML.

  1. Voltage-Gated Potassium Channel Antibody Paraneoplastic Limbic Encephalitis Associated with Acute Myeloid Leukemia

    PubMed Central

    Alcantara, Marion; Bennani, Omar; Verdure, Pierre; Leprêtre, Stéphane; Tilly, Hervé; Jardin, Fabrice

    2013-01-01

    Among paraneoplastic syndromes (PNS) associated with malignant hemopathies, there are few reports of PNS of the central nervous system and most of them are associated with lymphomas. Limbic encephalitis is a rare neurological syndrome classically diagnosed in the context of PNS. We report the case of a 81-year-old man who presented with a relapsed acute myeloid leukemia (AML) with minimal maturation. He was admitted for confusion with unfavorable evolution as he presented a rapidly progressive dementia resulting in death. A brain magnetic resonance imaging, performed 2 months after the onset, was considered normal. An electroencephalogram showed non-specific bilateral slow waves. We received the results of the blood screening of neuronal autoanti-bodies after the patient's death and detected the presence of anti-voltage-gated potassium channel (VGKC) antibodies at 102 pmol/l (normal at <30 pmol/l). Other etiologic studies, including the screening for another cause of rapidly progressive dementia, were negative. To our knowledge, this is the first case of anti-VGKC paraneoplastic limbic encephalitis related to AML. PMID:23898271

  2. 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.

  3. 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

  4. 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.

  5. Natural distribution of environmental radon daughters in the different brain areas of an Alzheimer Disease victim

    PubMed Central

    Momčilović, Berislav; Lykken, Glenn I; Cooley, Marvin

    2006-01-01

    Background Radon is a ubiquitous noble gas in the environment and a primary source of harmful radiation exposure for humans; it decays in a cascade of daughters (RAD) by releasing the cell damaging high energy alpha particles. Results We studied natural distribution of RAD 210Po and 210Bi in the different parts of the postmortem brain of 86-year-old woman who had suffered from Alzheimer's disease (AD). A distinct brain map emerged, since RAD distribution was different among the analyzed brain areas. The highest RAD irradiation (mSv·year-1) occurred in the decreasing order of magnitude: amygdale (Amy) >> hippocampus (Hip) > temporal lobe (Tem) ~ frontal lobe (Fro) > occipital lobe (Occ) ~ parietal lobe (Par) > substantia nigra (SN) >> locus ceruleus (LC) ~ nucleus basalis (NB); generally more RAD accumulated in the proteins than lipids of gray and white (gray > white) brain matter. Amy and Hip are particularly vulnerable brain structure targets to significant RAD internal radiation damage in AD (5.98 and 1.82 mSv·year-1, respectively). Next, naturally occurring RAD radiation for Tem and Fro, then Occ and Par, and SN was an order of magnitude higher than that in LC and NB; the later was within RAD we observed previously in the healthy control brains. Conclusion Naturally occurring environmental RAD exposure may dramatically enhance AD deterioration by selectively targeting brain areas of emotions (Amy) and memory (Hip). PMID:16965619

  6. Brain Injury in Autonomic, Emotional, and Cognitive Regulatory Areas in Patients with Heart Failure

    PubMed Central

    Woo, Mary A.; Kumar, Rajesh; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.

    2009-01-01

    Background Heart failure (HF) is accompanied by autonomic, emotional, and cognitive deficits, indicating brain alterations. Reduced gray matter volume and isolated white matter infarcts occur in HF, but the extent of damage is unclear. Using magnetic resonance T2 relaxometry, we evaluated the extent of injury across the entire brain in HF. Methods and Results Proton-density and T2-weighted images were acquired from 13 HF (age 54.6 ± 8.3 years; 69% male, LVEF 0.28 ± 0.07) and 49 controls (50.6 ± 7.3 years, 59% male). Whole brain maps of T2 relaxation times were compared at each voxel between groups using analysis of covariance (covariates: age and gender). Higher T2 relaxation values, indicating injured brain areas (p < 0.005), emerged in sites that control autonomic, analgesic, emotional, and cognitive functions (hypothalamus, raphé magnus, cerebellar cortex, deep nuclei and vermis; temporal, parietal, prefrontal, occipital, insular, cingulate, and ventral frontal cortices; corpus callosum; anterior thalamus; caudate nuclei; anterior fornix and hippocampus). No brain areas showed higher T2 values in control vs. HF subjects. Conclusions Brain structural injury emerged in areas involved in autonomic, pain, mood, language, and cognitive function in HF patients. Comorbid conditions accompanying HF may result from neural injury associated with the syndrome. PMID:19327623

  7. The retinal projectome reveals brain-area-specific visual representations generated by ganglion cell diversity.

    PubMed

    Robles, Estuardo; Laurell, Eva; Baier, Herwig

    2014-09-22

    Visual information is transmitted to the vertebrate brain exclusively via the axons of retinal ganglion cells (RGCs). The functional diversity of RGCs generates multiple representations of the visual environment that are transmitted to several brain areas. However, in no vertebrate species has a complete wiring diagram of RGC axonal projections been constructed. We employed sparse genetic labeling and in vivo imaging of the larval zebrafish to generate a cellular-resolution map of projections from the retina to the brain. Our data define 20 stereotyped axonal projection patterns, the majority of which innervate multiple brain areas. Morphometric analysis of pre- and postsynaptic RGC structure revealed more than 50 structural RGC types with unique combinations of dendritic and axonal morphologies, exceeding current estimates of RGC diversity in vertebrates. These single-cell projection mapping data indicate that specific projection patterns are nonuniformly specified in the retina to generate retinotopically biased visual maps throughout the brain. The retinal projectome also successfully predicted a functional subdivision of the pretectum. Our data indicate that RGC projection patterns are precisely coordinated to generate brain-area-specific visual representations originating from RGCs with distinct dendritic morphologies and topographic distributions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. [Study on corresponding areas the liver and lung channels in brain with fMRI].

    PubMed

    Xu, Fang-Ming; Xie, Peng; Lü, Fa-Jin; Mou, Jun; Li, Yong-Mei; Zhao, Jian-Nong; Chen, Wei-Juan; Gong, Qi-Yong; Zhao, Li-Bo; Liu, Qing-Jun; Shen, Lin; Zhai, Hong; Yang, De-Yu

    2007-10-01

    To explore distribution of the Liver and Lung Channels in the brain so as to provide imaging basis for construction of channel theory in the brain. Sixty healthy student volunteers were randomly divided into a Liver Channel group (I) and a Lung Channel group (II), and the each group was further divided into five subgroups with 6 volunteers in each subgroup, based on five-shu-point principles which, were Dadun (LR 1, I 1), Xingjian (LR 2, I 2), Taichong (LR 3, I 3), Zhongfeng (LR 4, I 4), Ququan (LR 8, I 5), Shaoshang (LU 11, II 1), Yuji (LU 10, II 2), Taiyuan (LU 9, II 3), Jingqu (LU 8, II 4), and Chize (LU 5, II 5), respectively. In order to observe the brain activating patterns during acupuncture at the different acupoints, functional magnetic resonance imaging (fMRI) technique was adopted. All image data were then analyzed with SPM 2 software. The statistical parameter gram was composed of the pixel P < 0.01, and anatomic location was made according to Talairach coordinate, attaining experimentally activated areas, and the commonly activated area of five-shu-point of each channel was considered as the brain distribution of the Liver and Lung Channels. The common areas activated by the five-shu-points of the Liver Channel were homolateral Brodmann area (BA) 34, BA 47, red nucleus, contralateral BA 19, BA 30, BA 39, the superior parietal lobule, cerebellum decline, and bilateral BA 3 and culmen. The common areas activated by the five-shu-points of the Lung Channels included homolateral BA 2, BA 18, BA 35, and contralateral BA 9 and substania nigra. There are relatively specific corresponding brain areas for the Liver and Lung Channels, indicating that there is possible relatively specific connection between channels and the brain.

  9. The experience-dependent maturation of prefronto-limbic circuits and the origin of developmental psychopathology: implications for the pathogenesis and therapy of behavioural disorders.

    PubMed

    Braun, Katharina; Bock, Jörg

    2011-09-01

    The maturation of prefronto-limbic neuronal pathways that mediate essential affective and social regulatory functions is experience dependent. Immediately after birth the infant's affective experiences, especially those embedded in the relationship with the primary caregiver, trigger the reorganization and adaptive fine-tuning of synaptic circuits. Research in humans and in animal models supports the hypothesis that socio-emotional deprivation and emotional trauma during early childhood may leave 'scars' in prefronto-limbic function, brain regions that are essential for emotional behaviour, learning, and memory. The focus of this review is to point out that mechanisms involved in structuring and optimizing neural circuits during brain development might also be used in moulding personality and behaviour during psychotherapy in the adult brain.

  10. Preoperative functional MRI localization of language areas in Chinese patients with brain tumors

    PubMed Central

    Xia, Hechun; Huang, Wei; Wu, Liang; Ma, Hui; Wang, Xiaodong; Chen, Xuexin; Sun, Shengyu; Jia, Xiaoxiong

    2012-01-01

    Ten Chinese patients with brain tumors involving language regions were selected. Preoperative functional MRI was performed to locate Broca's or Wernicke's area, and the cortex that was essential for language function was determined by electrocortical mapping. A site-by-site comparison between functional MRI and electrocortical mapping was performed with the aid of a neuronavigation device. Results showed that the sensitivity and specificity of preoperative functional MRI were 80.0% and 85.0% in Broca's area and 66.6% and 85.2% in Wernicke's area, respectively. These experimental findings indicate that functional MRI is an accurate, reliable technique with which to identify the location of Wernicke's area or Broca's area in patients with brain tumors. PMID:25657694

  11. Methylphenidate and atomoxetine inhibit social play behavior through prefrontal and subcortical limbic mechanisms in rats.

    PubMed

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

    2015-01-07

    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. Copyright © 2015 the authors 0270-6474/15/350161-09$15.00/0.

  12. The CLAIR model: Extension of Brodmann areas based on brain oscillations and connectivity.

    PubMed

    Başar, Erol; Düzgün, Aysel

    2016-05-01

    Since the beginning of the last century, the localization of brain function has been represented by Brodmann areas, maps of the anatomic organization of the brain. They are used to broadly represent cortical structures with their given sensory-cognitive functions. In recent decades, the analysis of brain oscillations has become important in the correlation of brain functions. Moreover, spectral connectivity can provide further information on the dynamic connectivity between various structures. In addition, brain responses are dynamic in nature and structural localization is almost impossible, according to Luria (1966). Therefore, brain functions are very difficult to localize; hence, a combined analysis of oscillation and event-related coherences is required. In this study, a model termed as "CLAIR" is described to enrich and possibly replace the concept of the Brodmann areas. A CLAIR model with optimum function may take several years to develop, but this study sets out to lay its foundation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. 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

  14. Understanding the links between vestibular and limbic systems regulating emotions.

    PubMed

    Rajagopalan, Archana; Jinu, K V; Sailesh, Kumar Sai; Mishra, Soumya; Reddy, Udaya Kumar; Mukkadan, Joseph Kurien

    2017-01-01

    Vestibular system, which consists of structures in the inner ear and brainstem, plays a vital role is body balance and patient well-being. In recent years, modulating this system by vestibular stimulation techniques are reported to be effective in stress relief and possibly patient's emotional well-being. Emotions refer to an aroused state involving intense feeling, autonomic activation, and related change in behavior, which accompany many of our conscious experiences. The limbic system is primarily involved in the regulation of emotions. Considering the extensive networks between vestibular and limbic system, it is likely that vestibular stimulation techniques may be useful in influencing emotions. Hence, we review here, the possible mechanisms through which vestibular system can influence emotions and highlight the necessary knowledge gaps, which warrants further research to develop vestibular stimulation techniques as a means to treat health conditions associated with emotional disturbances.

  15. Understanding the links between vestibular and limbic systems regulating emotions

    PubMed Central

    Rajagopalan, Archana; Jinu, K. V.; Sailesh, Kumar Sai; Mishra, Soumya; Reddy, Udaya Kumar; Mukkadan, Joseph Kurien

    2017-01-01

    Vestibular system, which consists of structures in the inner ear and brainstem, plays a vital role is body balance and patient well-being. In recent years, modulating this system by vestibular stimulation techniques are reported to be effective in stress relief and possibly patient's emotional well-being. Emotions refer to an aroused state involving intense feeling, autonomic activation, and related change in behavior, which accompany many of our conscious experiences. The limbic system is primarily involved in the regulation of emotions. Considering the extensive networks between vestibular and limbic system, it is likely that vestibular stimulation techniques may be useful in influencing emotions. Hence, we review here, the possible mechanisms through which vestibular system can influence emotions and highlight the necessary knowledge gaps, which warrants further research to develop vestibular stimulation techniques as a means to treat health conditions associated with emotional disturbances. PMID:28250668

  16. Loud Noise Exposure Produces DNA, Neurotransmitter and Morphological Damage within Specific Brain Areas

    PubMed Central

    Frenzilli, Giada; Ryskalin, Larisa; Ferrucci, Michela; Cantafora, Emanuela; Chelazzi, Silvia; Giorgi, Filippo S.; Lenzi, Paola; Scarcelli, Vittoria; Frati, Alessandro; Biagioni, Francesca; Gambardella, Stefano; Falleni, Alessandra; Fornai, Francesco

    2017-01-01

    Exposure to loud noise is a major environmental threat to public health. Loud noise exposure, apart from affecting the inner ear, is deleterious for cardiovascular, endocrine and nervous systems and it is associated with neuropsychiatric disorders. In this study we investigated DNA, neurotransmitters and immune-histochemical alterations induced by exposure to loud noise in three major brain areas (cerebellum, hippocampus, striatum) of Wistar rats. Rats were exposed to loud noise (100 dBA) for 12 h. The effects of noise on DNA integrity in all three brain areas were evaluated by using Comet assay. In parallel studies, brain monoamine levels and morphology of nigrostriatal pathways, hippocampus and cerebellum were analyzed at different time intervals (24 h and 7 days) after noise exposure. Loud noise produced a sudden increase in DNA damage in all the brain areas under investigation. Monoamine levels detected at 7 days following exposure were differently affected depending on the specific brain area. Namely, striatal but not hippocampal dopamine (DA) significantly decreased, whereas hippocampal and cerebellar noradrenaline (NA) was significantly reduced. This is in line with pathological findings within striatum and hippocampus consisting of a decrease in striatal tyrosine hydroxylase (TH) combined with increased Bax and glial fibrillary acidic protein (GFAP). Loud noise exposure lasting 12 h causes immediate DNA, and long-lasting neurotransmitter and immune-histochemical alterations within specific brain areas of the rat. These alterations may suggest an anatomical and functional link to explain the neurobiology of diseases which prevail in human subjects exposed to environmental noise. PMID:28694773

  17. The effects of acetaldehyde on nicotine-induced transmitter levels in young and adult brain areas.

    PubMed

    Sershen, H; Shearman, E; Fallon, S; Chakraborty, G; Smiley, J; Lajtha, A

    2009-08-14

    The aim of the present study was to examine the effect of acetaldehyde administration on neurotransmitters in the presence of nicotine in brain areas associated with cognition and reward. We assayed these effects via microdialysis in conscious freely moving male Sprague-Dawley rats. It was reported that low doses of acetaldehyde enhance nicotine self-administration in young, but not in adult rats. Since nicotine enhances reward and learning, while acetaldehyde is reported to enhance reward but inhibit learning, acetaldehyde thus would be likely to stimulate reward without stimulating learning. We hoped that examining the effects of acetaldehyde (on nicotine-mediated neurotransmitter changes) would help to distinguish reward mechanisms less influenced by learning mechanisms. To avoid the aversive effect of acetaldehyde, we used a low dose of acetaldehyde (0.16 mg/kg) administered after nicotine (0.3mg/kg). We analyzed six brain regions: nucleus accumbens shell (NAccS), ventral tegmental area (VTA), ventral and dorsal hippocampus (VH and DH), and prefrontal and medial temporal cortex (PFC, MTC), assaying dopamine (DA), norepinephrine (NE) and serotonin (5-HT) and their metabolites in young and adult rats. The effect of acetaldehyde on nicotine-induced transmitter changes was different in young as compared to adult rat brain regions. In the NAccS of the young, DA was not affected while NE and 5-HT were increased. In the adult in this area DA and NE were decreased, while 5-HT was not altered. In other areas also in many cases, the effect of acetaldehyde in the young and in the adult was different. As an example, acetaldehyde administration increased NE in young and decreased NE in adult DH. We found stimulation of nicotine-induced changes by acetaldehyde in seven instances - six of these were observed in areas in young brain, NE in four areas (NAccS, DH, VH, and PFC), and 5-HT in two (NAccS and DH). Only one increase was noted in adult brain (DA in VTA). Inhibition of

  18. Structural Plasticity of Dentate Granule Cell Mossy Fibers During the Development of Limbic Epilepsy

    PubMed Central

    Danzer, Steve C.; He, Xiaoping; Loepke, Andreas W.; McNamara, James O.

    2009-01-01

    Altered granule cell≫CA3 pyramidal cell synaptic connectivity may contribute to the development of limbic epilepsy. To explore this possibility, granule cell giant mossy fiber bouton plasticity was examined in the kindling and pilocarpine models of epilepsy using green fluorescent protein-expressing transgenic mice. These studies revealed significant increases in the frequency of giant boutons with satellite boutons 2 days and 1 month after pilocarpine status epilepticus, and increases in giant bouton area at 1 month. Similar increases in giant bouton area were observed shortly after kindling. Finally, both models exhibited plasticity of mossy fiber giant bouton filopodia, which contact GABAergic interneurons mediating feedforward inhibition of CA3 pyramids. In the kindling model, however, all changes were fleeting, having resolved by 1 month after the last evoked seizure. Together, these findings demonstrate striking structural plasticity of granule cell mossy fiber synaptic terminal structure in two distinct models of adult limbic epileptogenesis. We suggest that these plasticities modify local connectivities between individual mossy fiber terminals and their targets, inhibitory interneurons, and CA3 pyramidal cells potentially altering the balance of excitation and inhibition during the development of epilepsy. PMID:19294647

  19. Limbic encephalitis. A rare presentation of the small-cell lung carcinoma.

    PubMed

    den Hollander, A M; van Hulst, A M; Meerwaldt, J D; Haasjes, J G

    1989-11-01

    Two patients with an acute organic brain syndrome and accompanying neurological symptoms are described. Extensive work up showed that both patients suffered from small-cell lung cancer. Cerebral metastases were absent. Following chemotherapy and radiotherapy to the primary tumor one of the two patients showed a complete remission of psychiatric symptoms for one year. A paraneoplastic origin of this syndrome, in the literature known as limbic encephalitis, is postulated. The exact cause of this syndrome is yet unknown. Recent research reveals data indicating an immunological pathogenesis. The major clinical importance of this (neuro)-psychiatric syndrome is that its appearance may serve as a warning sign for an occult malignancy; furthermore, effective treatment of the primary malignancy can reverse the encephalitis. Thus antitumor therapy can result in a prolonged survival and considerably improved quality of life.

  20. Laterality of brain areas associated with arithmetic calculations revealed by functional magnetic resonance imaging.

    PubMed

    Zhang, Yun-ting; Zhang, Quan; Zhang, Jing; Li, Wei

    2005-04-20

    Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions: arithmetic calculation may be one of these phenomena. In this study, first, laterality of brain areas associated with arithmetic calculations was revealed by functional magnetic resonance imaging (fMRI). Second, the relationship among laterality, handedness, and types of arithmetic task was assessed. Third, we postulate possible reasons for laterality. Using a block-designed experiment, twenty-five right-handed and seven left-handed healthy volunteers carried out simple calculations, complex calculations and proximity judgments. T1WI and GRE-EPI fMRI were performed with a GE 1.5T whole body MRI scanner. Statistical parametric mapping (SPM99) was used to process data and localize functional areas. Numbers of activated voxels were recorded to calculate laterality index for evaluating the laterality of functional brain areas. For both groups, the activation of functional areas in the frontal lobe showed a tendency towards the nonpredominant hand side, but the functional areas in the inferior parietal lobule had left laterality. During simple and complex calculations, the laterality indices of the prefrontal cortex and premotor area were higher in the right-handed group than that in the left-handed group, whereas the laterality of the inferior parietal lobule had no such significant difference. In both groups, when the difficulty of the task increased, the laterality of the prefrontal cortex, premotor area, and inferior parietal lobule decreased, but the laterality of posterior part of the inferior frontal gyrus increased. The laterality of the functional brain areas associated with arithmetic calculations can be detected with fMRI. The laterality of the functional areas was related to handedness and task difficulty.

  1. Decreased Activation of Subcortical Brain Areas in the Motor Fatigue State: An fMRI Study

    PubMed Central

    Hou, Li J.; Song, Zheng; Pan, Zhu J.; Cheng, Jia L.; Yu, Yong; Wang, Jun

    2016-01-01

    One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus, and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e., thalamus and basal ganglia areas) are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state. PMID:27536264

  2. Is 2+2=4? Meta-analyses of brain areas needed for numbers and calculations.

    PubMed

    Arsalidou, Marie; Taylor, Margot J

    2011-02-01

    Most of us use numbers daily for counting, estimating quantities or formal mathematics, yet despite their importance our understanding of the brain correlates of these processes is still evolving. A neurofunctional model of mental arithmetic, proposed more than a decade ago, stimulated a substantial body of research in this area. Using quantitative meta-analyses of fMRI studies we identified brain regions concordant among studies that used number and calculation tasks. These tasks elicited activity in a set of common regions such as the inferior parietal lobule; however, the regions in which they differed were most notable, such as distinct areas of prefrontal cortices for specific arithmetic operations. Given the current knowledge, we propose an updated topographical brain atlas of mental arithmetic with improved interpretative power.

  3. Resting functional connectivity in patients with brain tumors in eloquent areas

    PubMed Central

    Martino, Juan; Honma, Susanne M.; Findlay, Anne M.; Guggisberg, Adrian G.; Kirsch, Heidi E.; Berger, Mitchel S.; Nagarajan, Srikantan S.

    2014-01-01

    Objective Resection of brain tumors adjacent to eloquent areas represents a challenge in neurosurgery. If maximal resection is desired without inducing postoperative neurological deficits, a detailed knowledge of the functional topography in and around the tumor is crucial. The aim of the present work is to evaluate the value of preoperative magnetoencephalography (MEG) imaging of functional connectivity to predict the results of intraoperative electrical stimulation (IES) mapping, the clinical gold standard for neurosurgical localization of functional areas. Methods Resting-state whole-cortex MEG recordings were obtained from 57 consecutive subjects with focal brain tumors near or within motor, sensory or language areas. Neural activity was estimated using adaptive spatial filtering algorithms, and the mean imaginary coherence between the rest of the brain and voxels in and around brain tumors were compared to the mean imaginary coherence between the rest of the brain and contralesional voxels as an index of functional connectivity. IES mapping was performed in all subjects. The cortical connectivity pattern near the tumor was compared to IES results. Results Maps with decreased resting-state functional connectivity in the entire tumor area had a negative predictive value of 100% for absence of eloquent cortex during IES. Maps showing increased resting-state functional connectivity within the tumor area had a positive predictive value of 64% for finding language, motor or sensory cortical sites during IES mapping. Interpretation Preoperative resting state MEG connectivity analysis is a useful noninvasive tool to evaluate the functionality of the tissue surrounding tumors within eloquent areas, and could potentially contribute to surgical planning and patient counseling. PMID:21400562

  4. Inter-species activity correlations reveal functional correspondences between monkey and human brain areas

    PubMed Central

    Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G.; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A.; Vanduffel, Wim

    2012-01-01

    Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. In cases where functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assess similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by means of temporal correlation. Using natural vision data, we reveal regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This novel framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models. PMID:22306809

  5. Interspecies activity correlations reveal functional correspondence between monkey and human brain areas.

    PubMed

    Mantini, Dante; Hasson, Uri; Betti, Viviana; Perrucci, Mauro G; Romani, Gian Luca; Corbetta, Maurizio; Orban, Guy A; Vanduffel, Wim

    2012-02-05

    Evolution-driven functional changes in the primate brain are typically assessed by aligning monkey and human activation maps using cortical surface expansion models. These models use putative homologous areas as registration landmarks, assuming they are functionally correspondent. For cases in which functional changes have occurred in an area, this assumption prohibits to reveal whether other areas may have assumed lost functions. Here we describe a method to examine functional correspondences across species. Without making spatial assumptions, we assessed similarities in sensory-driven functional magnetic resonance imaging responses between monkey (Macaca mulatta) and human brain areas by temporal correlation. Using natural vision data, we revealed regions for which functional processing has shifted to topologically divergent locations during evolution. We conclude that substantial evolution-driven functional reorganizations have occurred, not always consistent with cortical expansion processes. This framework for evaluating changes in functional architecture is crucial to building more accurate evolutionary models.

  6. Characteristics in limbic encephalitis with anti-adenylate kinase 5 autoantibodies.

    PubMed

    Do, Le-Duy; Chanson, Eve; Desestret, Virginie; Joubert, Bastien; Ducray, François; Brugière, Sabine; Couté, Yohann; Formaglio, Maité; Rogemond, Veronique; Thomas-Antérion, Catherine; Borrega, Laura; Laurens, Brice; Tison, Francois; Curot, Jonathan; De Brouker, Thomas; Lebrun-Frenay, Christine; Delattre, Jean-Yves; Antoine, Jean-Christophe; Honnorat, Jerome

    2017-02-07

    To report 10 patients with limbic encephalitis (LE) and adenylate kinase 5 autoantibodies (AK5-Abs). We conducted a retrospective study in a cohort of 50 patients with LE with uncharacterized autoantibodies and identified a specific target using immunohistochemistry, Western blotting, immunoprecipitation, mass spectrometry, and cell-based assay. AK5 (a known autoantigen of LE) was identified as the target of antibodies in the CSFs and sera of 10 patients with LE (median age 64 years; range 57-80), which was characterized by subacute anterograde amnesia without seizure and sometimes preceded by a prodromal phase of asthenia or mood disturbances. Anterograde amnesia can be isolated, but some patients also complained of prosopagnosia, paroxysmal anxiety, or abnormal behavior. No associated cancer was observed. All 10 patients had bilateral hippocampal hypersignal on a brain MRI. CSF analysis generally showed a mild pleiocytosis with elevated immunoglobulin G index and oligoclonal bands, as well as high levels of tau protein with normal concentration of Aβ42 and phospho-tau, suggesting a process of neuronal death. Except for one patient, clinical response to immunotherapy was unfavorable, with persistence of severe anterograde amnesia. Two patients evolved to severe cognitive decline. Hippocampal atrophy was observed on control brain MRI. Using in vitro tests on hippocampal neurons, we did not identify clues suggesting a direct pathogenic role of AK5-Abs. AK5-Abs should be systematically considered in aged patients with subacute anterograde amnesia. Recognition of this disorder is important to develop new treatment strategies to prevent irreversible limbic damage. © 2017 American Academy of Neurology.

  7. Eyelid apraxia associated with deep brain stimulation of the periaqueductal gray area.

    PubMed

    Langevin, Jean-Philippe; Srikandarajah, Nisaharan; Krahl, Scott E; Gorgulho, Alessandra; Behnke, Eric; Malkasian, Dennis; DeSalles, Antonio A F

    2014-09-01

    We report a patient with eyelid apraxia following deep brain stimulation of the periaqueductal gray area. Based on the position of our electrode, we argue that the phenomenon is linked to inhibition of the nearby central caudal nucleus of the oculomotor nucleus by high frequency stimulation.

  8. Identification of brain areas sensitive to the toxic effects of sparteine.

    PubMed

    Meraz Medina, T; Bañuelos Pineda, Jacinto; Gómez Rodiles, Carmen Cecilia; Vallejo, Salvador Jiménez; Zamora, Ricardo Solís; García López, Pedro Macedonio

    2017-01-01

    Sparteine is one of the most toxic quinolizidine alkaloids found in leguminous plants. Several studies have demonstrated that sparteine affects the nervous system, blocking the nervous ganglion, producing antimuscarinic effects, depressing the central nervous system and causing neuronal necrosis. However, there are no reports identifying the areas of the brain that are sensitive to the toxic effects of this alkaloid. 32 adult Wistar rats were on study, sixteen were implanted with an intracerebral stainless steel cannula and randomly assigned to a control or experimental group (n=8). Animals, control and experimental, received daily intraventricular (ICV) injections of a sparteine or a sterile water solution for five consecutive days. Additionally, two groups of animals (8 rats each) received daily intraperotineal injections (IP) of a sparteine or sterile water solution for five consecutive days. 72h after the last dose, the animals were sacrificed, their brains removed, fixed and embedded in paraffin to obtain 10μm tissue slices. Brain slices were stained with H&E and evaluated under a light microscope. The main brain structures sensitive to sparteine were the cerebral cortex (frontal, fronto-parietal and striate) olfactory and amygdaloid areas, the ventromedial hypothalamic nucleus, the Purkinje cells in the cerebellum, and the CA1, CA3 and dentate gyrus regions of the hippocampus. Administration of sparteine, via ICV or IP, caused neuronal necrosis in brain structures, mainly related with cholinergic pathways.

  9. GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans.

    PubMed

    van Bloemendaal, Liselotte; IJzerman, Richard G; Ten Kulve, Jennifer S; Barkhof, Frederik; Konrad, Robert J; Drent, Madeleine L; Veltman, Dick J; Diamant, Michaela

    2014-12-01

    Gut-derived hormones, such as GLP-1, have been proposed to relay information to the brain to regulate appetite. GLP-1 receptor agonists, currently used for the treatment of type 2 diabetes (T2DM), improve glycemic control and stimulate satiety, leading to decreases in food intake and body weight. We hypothesized that food intake reduction after GLP-1 receptor activation is mediated through appetite- and reward-related brain areas. Obese T2DM patients and normoglycemic obese and lean individuals (n = 48) were studied in a randomized, crossover, placebo-controlled trial. Using functional MRI, we determined the acute effects of intravenous administration of the GLP-1 receptor agonist exenatide, with or without prior GLP-1 receptor blockade using exendin 9-39, on brain responses to food pictures during a somatostatin pancreatic-pituitary clamp. Obese T2DM patients and normoglycemic obese versus lean subjects showed increased brain responses to food pictures in appetite- and reward-related brain regions (insula and amygdala). Exenatide versus placebo decreased food intake and food-related brain responses in T2DM patients and obese subjects (in insula, amygdala, putamen, and orbitofrontal cortex). These effects were largely blocked by prior GLP-1 receptor blockade using exendin 9-39. Our findings provide novel insights into the mechanisms by which GLP-1 regulates food intake and how GLP-1 receptor agonists cause weight loss.

  10. Monocrotaline: Histological Damage and Oxidant Activity in Brain Areas of Mice

    PubMed Central

    Honório Junior, José Eduardo Ribeiro; Vasconcelos, Germana Silva; Rodrigues, Francisca Taciana Sousa; Sena Filho, José Guedes; Barbosa-Filho, José Maria; Aguiar, Carlos Clayton Torres; Leal, Luzia Kalyne Almeida Moreira; Soares, Pedro Marcos Gomes; Woods, David John; Fonteles, Marta Maria de França; Vasconcelos, Silvânia Maria Mendes

    2012-01-01

    This work was designed to study MCT effect in histopathological analysis of hippocampus (HC) and parahippocampal cortex (PHC) and in oxidative stress (OS) parameters in brain areas such as hippocampus (HC), prefrontal cortex (PFC), and striatum (ST). Swiss mice (25–30 g) were administered a single i.p. dose of MCT (5, 50, or 100 mg/kg) or 4% Tween 80 in saline (control group). After 30 minutes, the animals were sacrificed by decapitation and the brain areas (HC, PHC, PFC, or ST) were removed for histopathological analysis or dissected and homogenized for measurement of OS parameters (lipid peroxidation, nitrite, and catalase) by spectrophotometry. Histological evaluation of brain structures of rats treated with MCT (50 and 100 mg/kg) revealed lesions in the hippocampus and parahippocampal cortex compared to control. Lipid peroxidation was evident in all brain areas after administration of MCT. Nitrite/nitrate content decreased in all doses administered in HC, PFC, and ST. Catalase activity was increased in the MCT group only in HC. In conclusion, monocrotaline caused cell lesions in the hippocampus and parahippocampal cortex regions and produced oxidative stress in the HC, PFC, and ST in mice. These findings may contribute to the neurological effects associated with this compound. PMID:23251721

  11. Widespread Brain Areas Engaged during a Classical Auditory Streaming Task Revealed by Intracranial EEG

    PubMed Central

    Dykstra, Andrew R.; Halgren, Eric; Thesen, Thomas; Carlson, Chad E.; Doyle, Werner; Madsen, Joseph R.; Eskandar, Emad N.; Cash, Sydney S.

    2011-01-01

    The auditory system must constantly decompose the complex mixture of sound arriving at the ear into perceptually independent streams constituting accurate representations of individual sources in the acoustic environment. How the brain accomplishes this task is not well understood. The present study combined a classic behavioral paradigm with direct cortical recordings from neurosurgical patients with epilepsy in order to further describe the neural correlates of auditory streaming. Participants listened to sequences of pure tones alternating in frequency and indicated whether they heard one or two “streams.” The intracranial EEG was simultaneously recorded from sub-dural electrodes placed over temporal, frontal, and parietal cortex. Like healthy subjects, patients heard one stream when the frequency separation between tones was small and two when it was large. Robust evoked-potential correlates of frequency separation were observed over widespread brain areas. Waveform morphology was highly variable across individual electrode sites both within and across gross brain regions. Surprisingly, few evoked-potential correlates of perceptual organization were observed after controlling for physical stimulus differences. The results indicate that the cortical areas engaged during the streaming task are more complex and widespread than has been demonstrated by previous work, and that, by-and-large, correlates of bistability during streaming are probably located on a spatial scale not assessed – or in a brain area not examined – by the present study. PMID:21886615

  12. Motor directional tuning across brain areas: directional resonance and the role of inhibition for directional accuracy

    PubMed Central

    Mahan, Margaret Y.; Georgopoulos, Apostolos P.

    2013-01-01

    Motor directional tuning (Georgopoulos et al., 1982) has been found in every brain area in which it has been sought for during the past 30-odd years. It is typically broad, with widely distributed preferred directions and a population signal that predicts accurately the direction of an upcoming reaching movement or isometric force pulse (Georgopoulos et al., 1992). What is the basis for such ubiquitous directional tuning? How does the tuning come about? What are the implications of directional tuning for understanding the brain mechanisms of movement in space? This review addresses these questions in the light of accumulated knowledge in various sub-fields of neuroscience and motor behavior. It is argued (a) that direction in space encompasses many aspects, from vision to muscles, (b) that there is a directional congruence among the central representations of these distributed “directions” arising from rough but orderly topographic connectivities among brain areas, (c) that broad directional tuning is the result of broad excitation limited by recurrent and non-recurrent (i.e., direct) inhibition within the preferred direction loci in brain areas, and (d) that the width of the directional tuning curve, modulated by local inhibitory mechanisms, is a parameter that determines the accuracy of the directional command. PMID:23720612

  13. Dynamics of brain activity in motor and frontal cortical areas during music listening: a magnetoencephalographic study.

    PubMed

    Popescu, Mihai; Otsuka, Asuka; Ioannides, Andreas A

    2004-04-01

    There are formidable problems in studying how 'real' music engages the brain over wide ranges of temporal scales extending from milliseconds to a lifetime. In this work, we recorded the magnetoencephalographic signal while subjects listened to music as it unfolded over long periods of time (seconds), and we developed and applied methods to correlate the time course of the regional brain activations with the dynamic aspects of the musical sound. We showed that frontal areas generally respond with slow time constants to the music, reflecting their more integrative mode; motor-related areas showed transient-mode responses to fine temporal scale structures of the sound. The study combined novel analysis techniques designed to capture and quantify fine temporal sequencing from the authentic musical piece (characterized by a clearly defined rhythm and melodic structure) with the extraction of relevant features from the dynamics of the regional brain activations. The results demonstrated that activity in motor-related structures, specifically in lateral premotor areas, supplementary motor areas, and somatomotor areas, correlated with measures of rhythmicity derived from the music. These correlations showed distinct laterality depending on how the musical performance deviated from the strict tempo of the music score, that is, depending on the musical expression.

  14. 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

  15. Weight gain following subthalamic nucleus deep brain stimulation: a PET study.

    PubMed

    Sauleau, Paul; Le Jeune, Florence; Drapier, Sophie; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Lalys, Florent; Robert, Gabriel; Drapier, Dominique; Vérin, Marc

    2014-12-01

    Several hypotheses have been put forward to explain weight gain after deep brain stimulation (DBS), but none provides a fully satisfactory account of this adverse effect. We analyzed the correlation between changes in brain metabolism (using positron emission tomography [PET] imaging) and weight gain after bilateral subthalamic nucleus DBS in patients with Parkinson's disease. Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose 3 months before and 4 months after the start of subthalamic nucleus deep brain stimulation in 23 patients with Parkinson's disease. Motor complications (United Parkinson's Disease Rating Scale [UPDRS]-IV scores) and dopaminergic medication were included in the analysis to control for their possible influence on brain metabolism. Mean ± standard deviation (SD) body mass index increased significantly by 0.8 ± 1.5 kg/m(2) (P = 0.03). Correlations were found between weight gain and changes in brain metabolism in limbic and associative areas, including the orbitofrontal cortex (Brodmann areas [BAs] 10 and 11), lateral and medial parts of the temporal lobe (BAs 20, 21, 22,39 and 42), anterior cingulate cortex (BA 32), and retrosplenial cortex (BA 30). However, we found no correlation between weight gain and metabolic changes in sensorimotor areas. These findings suggest that changes in associative and limbic processes contribute to weight gain after subthalamic nucleus DBS in Parkinson's disease.

  16. 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

    2017-01-23

    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, 2017. © 2017 Wiley Periodicals, Inc.

  17. Trajectories of cortical surface area and cortical volume maturation in normal brain development

    PubMed Central

    Ducharme, Simon; Albaugh, Matthew D.; Nguyen, Tuong-Vi; Hudziak, James J.; Mateos-Pérez, J.M.; Labbe, Aurelie; Evans, Alan C.; Karama, Sherif

    2015-01-01

    This is a report of developmental trajectories of cortical surface area and cortical volume in the NIH MRI Study of Normal Brain Development. The quality-controlled sample included 384 individual typically-developing subjects with repeated scanning (1–3 per subject, total scans n=753) from 4.9 to 22.3 years of age. The best-fit model (cubic, quadratic, or first-order linear) was identified at each vertex using mixed-effects models, with statistical correction for multiple comparisons using random field theory. Analyses were performed with and without controlling for total brain volume. These data are provided for reference and comparison with other databases. Further discussion and interpretation on cortical developmental trajectories can be found in the associated Ducharme et al.׳s article “Trajectories of cortical thickness maturation in normal brain development – the importance of quality control procedures” (Ducharme et al., 2015) [1]. PMID:26702424

  18. Identification of hypometabolic areas in the brain using brain imaging and hyperbaric oxygen.

    PubMed

    Neubauer, R A; Gottlieb, S F; Miale, A

    1992-06-01

    Current neurologic assessments consider idling neurons and ischemic penumbras to be metabolically lethargic and electrically nonfunctional or nonviable. Diagnosis, prognosis, and therapeutics of central nervous system dysfunctions require differentiation between viable and nonviable neurons. It is necessary to develop and document efficacious and safe techniques for reactivating idling neurons. The authors present a case study of a near drowning 12 years earlier. Areas of cortical hypometabolism were identified by using SPECT imaging in conjunction with hyperbaric oxygen therapy (HBOT). Delayed imaging after HBOT (1 hour, 1.5 atm abs) suggested viable but metabolically lethargic neurons. After HBOT (80 1-hour treatments, monoplace chamber, 1.5 atm abs), marked improvements in cognitive and motor functioning were demonstrated. The data support the hypothesis that idling neurons and ischemic penumbras, when given sufficient oxygen, are capable of reactivation. Thus, changes in tracer distribution after a single exposure to HBOT may be a good prognostic indicator of viable neurons. HBOT may be valuable not only in recovery from anoxic encephalopathy but also from other traumatic and nontraumatic dysfunctions of the central nervous system, including stroke. HBOT in conjunction with physical and rehabilitative therapy may help reactivated idling neurons to remain permanently active.

  19. Stereotaxic Surgery for Excitotoxic Lesion of Specific Brain Areas in the Adult Rat

    PubMed Central

    Kirby, Elizabeth D.; Jensen, Kelly; Goosens, Ki A.; Kaufer, Daniela

    2012-01-01

    Many behavioral functions in mammals, including rodents and humans, are mediated principally by discrete brain regions. A common method for discerning the function of various brain regions for behavior or other experimental outcomes is to implement a localized ablation of function. In humans, patient populations with localized brain lesions are often studied for deficits, in hopes of revealing the underlying function of the damaged area. In rodents, one can experimentally induce lesions of specific brain regions. Lesion can be accomplished in several ways. Electrolytic lesions can cause localized damage but will damage a variety of cell types as well as traversing fibers from other brain regions that happen to be near the lesion site. Inducible genetic techniques using cell-type specific promoters may also enable site-specific targeting. These techniques are complex and not always practical depending on the target brain area. Excitotoxic lesion using stereotaxic surgery, by contrast, is one of the most reliable and practical methods of lesioning excitatory neurons without damaging local glial cells or traversing fibers. Here, we present a protocol for stereotaxic infusion of the excitotoxin, N-methyl-D-aspartate (NMDA), into the basolateral amygdala complex. Using anatomical indications, we apply stereotaxic coordinates to determine the location of our target brain region and lower an injection needle in place just above the target. We then infuse our excitotoxin into the brain, resulting in excitotoxic death of nearby neurons. While our experimental subject of choice is a rat, the same methods can be applied to other mammals, with the appropriate adjustments in equipment and coordinates. This method can be used on a variety of brain regions, including the basolateral amygdala1-6, other amygdala nuclei6, 7, hippocampus8, entorhinal cortex9 and prefrontal cortex10. It can also be used to infuse biological compounds such as viral vectors1, 11. The basic stereotaxic

  20. Interaction of some limbic structures which exert inhibitory effect on corticosterone secretion.

    PubMed

    Suárez, M; Perassi, N I

    1990-12-01

    The interaction between limbic structures which exert inhibitory influence on corticosterone secretion was investigated in the rat. The following experiments were performed: 1) electrical stimulation at mammillary medial nucleus (MMN) in rats with lesioned anterodrosal thalami nucleus (ADTN) or intermediate tegmental area; 2) electrical stimulation at ADTN in rats with lesioned retrosplenial cortex (RC). Bilateral stimulation at MMN in ADTN or RC-lesioned rats produces an increase in plasma corticosterone concentration. In animals with lesioned RC, values of plasma corticosterone after stimulation at ADTN were higher than before stimulation. Taking into consideration that electrical stimulation of MMN or ADTN in intact rats produces a decrease in plasma corticosterone concentration, these studies demonstrate that MMN and ADTN exert inhibitory influence on corticoadrenal activity only when their projection areas remain intact.

  1. Citicoline Affects Appetite and Cortico-Limbic Responses to Images of High Calorie Foods

    PubMed Central

    Killgore, William D. S.; Ross, Amy J.; Kamiya, Toshi; Kawada, Yoko; Renshaw, Perry F.; Yurgelun-Todd, Deborah A.

    2011-01-01

    Cytidine-5’-diphosphocholine (citicoline) has a variety of cognitive enhancing, neuroprotective, and neuroregenerative properties. In cocaine-addicted individuals, citicoline has been shown to increase brain dopamine levels and reduce cravings. The effects of this compound on appetite, food cravings, and brain responses to food are unknown. We compared the effects of treatment with citicoline (500 mg/day versus 2000 mg/day) for six weeks on changes in appetite ratings, weight, and cortico-limbic responses to images of high calorie foods using functional magnetic resonance imaging (fMRI). After six weeks, there was no significant change in weight status, although significant declines in appetite ratings were observed for the 2000 mg/day group. The higher dose group also showed significant increases in functional brain responses to food stimuli within the amygdala, insula, and lateral orbitofrontal cortex. Increased activation in these regions correlated with declines in appetite ratings. These preliminary findings suggest a potential usefulness of citicoline in modulating appetite, but further research is warranted. PMID:19260039

  2. Hypometabolism of watershed areas of the brain in HTLV-1-associated myelopathy/tropical spastic paraparesis.

    PubMed

    Taniguchi, Akitoshi; Mochizuki, Hitoshi; Nagamachi, Shigeki; Ebihara, Yuka; Ishii, Nobuyuki; Shiomi, Kazutaka; Nakazato, Masamitsu

    2015-11-01

    In previous studies of human T-lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), areas of slow blood flow in the spinal cord were related to pathological changes. While the pathological changes in the brain are milder than those in the spinal cord, they are also more significant in sites with slow blood flow. In this study, we investigated brain glucose metabolism in slow blood flow areas using fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). Clinical features and brain (18)F-FDG-PET parameters were analyzed in six patients with HAM/TSP. For comparison of PET data, eight healthy volunteers were enrolled as normal controls (NLs). Glucose metabolism in the watershed areas of the middle and posterior cerebral arteries, as compared with that in the occipital lobes as a control, was significantly lower in HAM/TSP patients than in NLs. This result confirmed the relationship between slow blood flow areas and hypometabolism in HAM/TSP, and is consistent with previous findings that pathological changes are accentuated in sites with slow blood flow.

  3. Dexmedetomidine and ketamine show distinct patterns of cell degeneration and apoptosis in the developing rat neonatal brain.

    PubMed

    Pancaro, Carlo; Segal, B Scott; Sikes, Robert W; Almeer, Zainab; Schumann, Roman; Azocar, Ruben J; Marchand, James E

    2016-12-01

    Early exposure to common anesthetic and sedative agents causes widespread brain cell degeneration and apoptosis in the developing rat brain, associated with persistent learning deficits in rats. This study was designed to determine whether the α2 adrenergic receptor agonist, dexmedetomidine, produces brain cell degeneration and apoptosis in postnatal day-7 rats in the same brain areas when compared to ketamine. Systemic saline, ketamine 20 mg/kg, or dexmedetomidine at 30 or 45 μg/kg were given six times to postnatal day 7 rats (n  =  6/group) every 90 min. Twenty-four hours after the initial injection, brain regions were processed and analyzed for cell degeneration using the silver stain and for apoptosis using activated caspase-3 immunohistochemistry. Exposure to ketamine resulted in significant cellular degeneration and apoptosis in limbic brain regions, but nonsignificant changes in primary sensory brain regions. In contrast, dexmedetomidine produced significant cellular degeneration and apoptosis in primary sensory brain regions, but nonsignificant changes in limbic regions. These data show that ketamine and dexmedetomidine result in anatomically distinct patterns of cell degeneration and apoptosis in the brains of 7-day-old rat pups. The meaning and the clinical significance of these findings remain to be established.

  4. Differential investment in visual and olfactory brain areas reflects behavioural choices in hawk moths

    PubMed Central

    Stöckl, Anna; Heinze, Stanley; Charalabidis, Alice; el Jundi, Basil; Warrant, Eric; Kelber, Almut

    2016-01-01

    Nervous tissue is one of the most metabolically expensive animal tissues, thus evolutionary investments that result in enlarged brain regions should also result in improved behavioural performance. Indeed, large-scale comparative studies in vertebrates and invertebrates have successfully linked differences in brain anatomy to differences in ecology and behaviour, but their precision can be limited by the detail of the anatomical measurements, or by only measuring behaviour indirectly. Therefore, detailed case studies are valuable complements to these investigations, and have provided important evidence linking brain structure to function in a range of higher-order behavioural traits, such as foraging experience or aggressive behaviour. Here, we show that differences in the size of both lower and higher-order sensory brain areas reflect differences in the relative importance of these senses in the foraging choices of hawk moths, as suggested by previous anatomical work in Lepidopterans. To this end we combined anatomical and behavioural quantifications of the relative importance of vision and olfaction in two closely related hawk moth species. We conclude that differences in sensory brain volume in these hawk moths can indeed be interpreted as differences in the importance of these senses for the animal’s behaviour. PMID:27185464

  5. Motor areas of the frontal cortex in patients with motor eloquent brain lesions.

    PubMed

    Bulubas, Lucia; Sabih, Jamil; Wohlschlaeger, Afra; Sollmann, Nico; Hauck, Theresa; Ille, Sebastian; Ringel, Florian; Meyer, Bernhard; Krieg, Sandro M

    2016-12-01

    OBJECTIVE Because of its huge clinical potential, the importance of premotor areas for motor function itself and plastic reshaping due to tumors or ischemic brain lesions has received increased attention. Thus, in this study the authors used navigated transcranial magnetic stimulation (nTMS) to investigate whether tumorous brain lesions induce a change in motor cortex localization in the human brain. METHODS Between 2010 and 2013, nTMS motor mapping was performed in a prospective cohort of 100 patients with brain tumors in or adjacent to the rolandic cortex. Spatial data analysis was performed by normalization of the individual motor maps and creation of overlays according to tumor location. Analysis of motor evoked potential (MEP) latencies was performed regarding mean overall latencies and potentially polysynaptic latencies, defined as latencies longer than 1 SD above the mean value. Hemispheric dominance, lesion location, and motor-function deficits were also considered. RESULTS Graphical analysis showed that motor areas were not restricted to the precentral gyrus. Instead, they spread widely in the anterior-posterior direction. An analysis of MEP latency showed that mean MEP latencies were shortest in the precentral gyrus and longest in the superior and middle frontal gyri. The percentage of latencies longer than 1 SD differed widely across gyri. The dominant hemisphere showed a greater number of longer latencies than the nondominant hemisphere (p < 0.0001). Moreover, tumor location-dependent changes in distribution of polysynaptic latencies were observed (p = 0.0002). Motor-function deficit did not show any statistically significant effect. CONCLUSIONS The distribution of primary and polysynaptic motor areas changes in patients with brain tumors and highly depends on tumor location. Thus, these data should be considered for resection planning.

  6. Brainstem and limbic encephalitis with paraneoplastic neuromyelitis optica.

    PubMed

    Moussawi, Khaled; Lin, David J; Matiello, Marcelo; Chew, Sheena; Morganstern, Daniel; Vaitkevicius, Henrikas

    2016-01-01

    The spectrum of disorders associated with anti-neuromyelitis optica (NMO) antibody is being extended to include infrequent instances associated with cancer. We describe a patient with brainstem and limbic encephalitis from NMO-immunoglobulin G in serum and cerebrospinal fluid in the context of newly diagnosed breast cancer. The neurological features markedly improved with excision of her breast cancer and immune suppressive therapy. This case further broadens the NMO spectrum disorders (NMOSD) by an association between NMOSD and cancer and raises the question of coincidental occurrence and the appropriate circumstances to search for a tumor in certain instances of NMO. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. 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.

  8. Behavioral effects of deep brain stimulation of different areas of the Papez circuit on memory- and anxiety-related functions.

    PubMed

    Hescham, Sarah; Jahanshahi, Ali; Meriaux, Céline; Lim, Lee Wei; Blokland, Arjan; Temel, Yasin

    2015-10-01

    Deep brain stimulation (DBS) has gained interest as a potential therapy for advanced treatment-resistant dementia. However, possible targets for DBS and the optimal stimulation parameters are not yet clear. Here, we compared the effects of DBS of the CA1 sub-region of the hippocampus, mammillothalamic tract, anterior thalamic nucleus, and entorhinal cortex in an experimental rat model of dementia. Rats with scopolamine-induced amnesia were assessed in the object location task with different DBS parameters. Moreover, anxiety-related side effects were evaluated in the elevated zero maze and open field. After sacrifice, we applied c-Fos immunohistochemistry to assess which memory-related regions were affected by DBS. When comparing all structures, DBS of the entorhinal cortex and CA1 sub-region was able to restore memory loss when a specific set of stimulation parameters was used. No anxiety-related side effects were found following DBS. The beneficial behavioral performance of CA1 DBS rats was accompanied with an activation of cells in the anterior cingulate gyrus. Therefore, we conclude that acute CA1 DBS restores memory loss possibly through improved attentional and cognitive processes in the limbic cortex. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Cortical plasticity catalyzed by prehabilitation enables extensive resection of brain tumors in eloquent areas.

    PubMed

    Rivera-Rivera, Paola A; Rios-Lago, Marcos; Sanchez-Casarrubios, Sandra; Salazar, Osman; Yus, Miguel; González-Hidalgo, Mercedes; Sanz, Ana; Avecillas-Chasin, Josué; Alvarez-Linera, Juan; Pascual-Leone, Alvaro; Oliviero, Antonio; Barcia, Juan A

    2017-04-01

    OBJECTIVE The extent of resection is the most important prognostic factor following brain glioma surgery. However, eloquent areas within tumors limit the extent of resection and, thus, critically affect outcomes. The authors hypothesized that presurgical suppression of the eloquent areas within a tumor by continuous cortical electrical stimulation, coupled with appropriate behavioral training ("prehabilitation"), would induce plastic reorganization and enable a more extensive resection. METHODS The authors report on 5 patients harboring gliomas involving eloquent brain areas within tumors as identified on intraoperative stimulation mapping. A grid of electrodes was placed over the residual tumor, and continuous cortical electrical stimulation was targeted to the functional areas. The stimulation intensity was adjusted daily to provoke a mild functional impairment while the function was intensively trained. RESULTS The stimulation intensity required to impair function increased progressively in all patients, and all underwent another operation a mean of 33.6 days later (range 27-37 days), when the maximal stimulation voltage in all active contacts induced no functional deficit. In all cases, a substantially more extensive resection of the tumor was possible. Intraoperative mapping and functional MRI demonstrated a plastic reorganization, and most previously demonstrated eloquent areas within the tumor were silent, while there was new functional activation of brain areas in the same region or toward the contralateral hemisphere. CONCLUSIONS Prehabilitation with continuous cortical electrical stimulation and appropriate behavioral training prior to surgery in patients with WHO Grade II and III gliomas affecting eloquent areas accelerate plastic changes. This can help maximize tumor resection and, thus, improve survival while maintaining function.

  10. Examining the gateway to the limbic system with diffusion tensor imaging: the perforant pathway in dementia.

    PubMed

    Kalus, Peter; Slotboom, Johannes; Gallinat, Jürgen; Mahlberg, Richard; Cattapan-Ludewig, Katja; Wiest, Roland; Nyffeler, Thomas; Buri, Caroline; Federspiel, Andrea; Kunz, Dieter; Schroth, Gerhard; Kiefer, Claus

    2006-04-15

    Current treatments for Alzheimer's disease (AD) are only able to slow the progression of mental deterioration, making early and reliable diagnosis an essential part of any promising therapeutic strategy. In the initial stages of AD, the first neuropathological alterations occur in the perforant pathway (PP), a large neuronal fiber tract located at the entrance to the limbic system. However, to date, there is no sensitive diagnostic tool for performing in vivo assessments of this structure. In the present bimodal magnetic resonance imaging (MRI) study, we examined 10 elderly controls, 10 subjects suffering from mild cognitive impairment (MCI), and 10 AD patients in order to evaluate the sensitivity of diffusion tensor imaging (DTI), a new MRI technique, for detecting changes in the PP. Furthermore, the diagnostic explanatory power of DTI data of the PP should be compared to high-resolution MRI volumetry and intervoxel coherences (COH) of the hippocampus and the entorhinal cortex, two limbic regions also involved in the pathophysiology of early AD. DTI revealed a marked decrease in COH values in the PP region of MCI (right side: 26%, left side: 29%, as compared to controls) and AD patients (right side: 37%, left side: 43%, as compared to controls). Reductions in COH values of the PP region were significantly correlated with cognitive impairment. DTI data of the PP zone were the only parameter differing significantly between control subjects and MCI patients, while the volumetric measures and the COH values of the hippocampus and the entorhinal cortex did not. DTI of medial temporal brain regions is a promising non-invasive tool for the in vivo diagnosis of the early/preclinical stages of AD.

  11. Local cerebral glucose utilization in the neocortical areas of the rat brain.

    PubMed

    Wree, A; Zilles, K; Schleicher, A

    1990-01-01

    The neocortex of the rat brain can be subdivided into regions of different local cerebral glucose utilization (LCGU). However, only a few neocortical areas can be delineated by differences in mean LCGUs between neighbouring areas. These area borders correspond exactly with cytoarchitectonically defined borders found in adjacent Nissl-stained preparations. On the other hand, nearly all of the architectonically defined area borders are also recognizable in the LCGU pictures, if differences in laminar distribution patterns of LCGU are taken into account. Furthermore, interareal differences in mean LCGU mainly reflect changes in layer IV, whereas layers II-III and V-VI show nearly identical LCGU values in all neocortical areas of the rat brain. The primary sensory areas exhibit the highest LCGU in layer IV, while the primary motor cortex shows a high LCGU in layer V. As the cytoarchitectonically defined pattern of the cortex is generally corroborated by the regional and laminar LCGU distribution, anatomical, metabolic and functional aspects of cortical architecture are associated.

  12. [Spectrofluorometric determination of dopamine in small areas of rat brain (author's transl)].

    PubMed

    López-Novoa, J M; Martínez-Conde, E; Fraile, A

    1977-03-01

    A method for the extraction and quantification of Dopamine from small areas of rat brain has been developed. The extraction with solvents eliminates the column cromatography separations and allows the simultaneous processing of a good number of samples. Sample retrieval is quite high (70%) and very reproducible. The evaluation was made from areas with a minimal weight of 0.225 g. The quantification of Dopamine was obtained using spectrofluorometric techniques, reading the fluorescence of the trihydroxy indol derivate. The linear relation between the instrument readings and the concentration of Dopamine is from 0 to 0.5 microng/ml. The maximal concentration of Dopamine was found in the decorticated cerebral hemispheres (1.485 microng/g), the next highest values in the diencephalon (1.046 microng/), and the minimal concentration in the cerebellum (0.283 microng/g). The concentration of the whole brain was 0.701 microng/g.

  13. Effect of hypoxia and pharmacological treatment on some enzyme activities in dog brain areas.

    PubMed

    Arrigoni, E; Benzi, G; Curti, D; Dagani, F; Gallico, S; Gorini, A; Mandelli, V; Marzatico, F; Moretti, A; Villa, R F

    1984-05-01

    The effects of nicergoline on changes in enzymatic activities induced by hypoxia and post-hypoxic recovery were studied in various brain areas of young-adult and mature Beagle dogs. In different fractions (homogenate in toto, purified mitochondria, crude synaptosomes, SM1 and SM2 synaptic mitochondria) the maximal rate (Vmax) was investigated of the more representative enzymatic activities of: a) glycolysis, b) Krebs' cycle, c) electron transfer chain, d) amino acid and acetylcholine metabolism, e) lysosomal function. The physiopathological conditions caused alterations in different enzymatic activities depending on the area and subfraction investigated. Nicergoline tended to antagonize some of these alterations. Its action was mainly on non-synaptic mitochondria by a "braking" effect on some key enzyme activities of mitochondrial metabolism (i.e. citrate synthase, cytochrome oxidase and glutamate dehydrogenase) which suggests a sparing action in the brain.

  14. Brain stimulation used as biofeedback in neuronal activation of the temporal lobe area in autistic children.

    PubMed

    Silva, Vernon Furtado da; Calomeni, Mauricio Rocha; Nunes, Rodolfo Alkmim Moreira; Pimentel, Carlos Elias; Martins, Gabriela Paes; Oliveira, Patrícia da Cruz Araruna; Silva, Patrícia Bagno; Silva, Alair Pedro Ribeiro de Souza E

    2016-08-01

    This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.

  15. 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.

  16. Uni- and multisensory brain areas are synchronised across spectators when watching unedited dance recordings.

    PubMed

    Jola, Corinne; McAleer, Phil; Grosbras, Marie-Hélène; Love, Scott A; Morison, Gordon; Pollick, Frank E

    2013-01-01

    The superior temporal sulcus (STS) and gyrus (STG) are commonly identified to be functionally relevant for multisensory integration of audiovisual (AV) stimuli. However, most neuroimaging studies on AV integration used stimuli of short duration in explicit evaluative tasks. Importantly though, many of our AV experiences are of a long duration and ambiguous. It is unclear if the enhanced activity in audio, visual, and AV brain areas would also be synchronised over time across subjects when they are exposed to such multisensory stimuli. We used intersubject correlation to investigate which brain areas are synchronised across novices for uni- and multisensory versions of a 6-min 26-s recording of an unfamiliar, unedited Indian dance recording (Bharatanatyam). In Bharatanatyam, music and dance are choreographed together in a highly intermodal-dependent manner. Activity in the middle and posterior STG was significantly correlated between subjects and showed also significant enhancement for AV integration when the functional magnetic resonance signals were contrasted against each other using a general linear model conjunction analysis. These results extend previous studies by showing an intermediate step of synchronisation for novices: while there was a consensus across subjects' brain activity in areas relevant for unisensory processing and AV integration of related audio and visual stimuli, we found no evidence for synchronisation of higher level cognitive processes, suggesting these were idiosyncratic.

  17. Cocaine induces DNA damage in distinct brain areas of female rats under different hormonal conditions.

    PubMed

    de Souza, Marilise F; Gonçales, Tierre A; Steinmetz, Aline; Moura, Dinara J; Saffi, Jenifer; Gomez, Rosane; Barros, Helena M T

    2014-04-01

    We evaluated levels of neuronal DNA damage after acute or repeated cocaine treatment in different brain areas of female rats after ovariectomy or sham surgery. Rats in the control and acute groups were given saline i.p., whereas in the repeated group were given 15 mg/kg, i.p., cocaine for 8 days. After a 10 day washout period, the control group was given saline i.p., whereas rats in the acute and repeated groups were given a challenge dose of 15 mg/kg, i.p., cocaine. After behavioural assessment, rats were killed and the cerebellum, hippocampus, hypothalamus, prefrontal cortex and striatum were dissected for the Comet assay. Acute cocaine exposure induced DNA damage in all brain areas. This effect persisted after repeated administration, except in the hypothalamus, where repeated treatment did not cause increased DNA damage. Sexual hormones exhibited a neuroprotective effect, decreasing cocaine-induced DNA damage in cycling rats in all brain areas. © 2014 Wiley Publishing Asia Pty Ltd.

  18. Uni- and multisensory brain areas are synchronised across spectators when watching unedited dance recordings

    PubMed Central

    Jola, Corinne; McAleer, Phil; Grosbras, Marie-Hélène; Love, Scott A.; Morison, Gordon; Pollick, Frank E.

    2013-01-01

    The superior temporal sulcus (STS) and gyrus (STG) are commonly identified to be functionally relevant for multisensory integration of audiovisual (AV) stimuli. However, most neuroimaging studies on AV integration used stimuli of short duration in explicit evaluative tasks. Importantly though, many of our AV experiences are of a long duration and ambiguous. It is unclear if the enhanced activity in audio, visual, and AV brain areas would also be synchronised over time across subjects when they are exposed to such multisensory stimuli. We used intersubject correlation to investigate which brain areas are synchronised across novices for uni- and multisensory versions of a 6-min 26-s recording of an unfamiliar, unedited Indian dance recording (Bharatanatyam). In Bharatanatyam, music and dance are choreographed together in a highly intermodal-dependent manner. Activity in the middle and posterior STG was significantly correlated between subjects and showed also significant enhancement for AV integration when the functional magnetic resonance signals were contrasted against each other using a general linear model conjunction analysis. These results extend previous studies by showing an intermediate step of synchronisation for novices: while there was a consensus across subjects' brain activity in areas relevant for unisensory processing and AV integration of related audio and visual stimuli, we found no evidence for synchronisation of higher level cognitive processes, suggesting these were idiosyncratic. PMID:24349687

  19. Brain areas associated with force steadiness and intensity during isometric ankle dorsiflexion in men and women.

    PubMed

    Yoon, Tejin; Vanden Noven, Marnie L; Nielson, Kristy A; Hunter, Sandra K

    2014-10-01

    Although maintenance of steady contractions is required for many daily tasks, there is little understanding of brain areas that modulate lower limb force accuracy. Functional magnetic resonance imaging was used to determine brain areas associated with steadiness and force during static (isometric) lower limb target-matching contractions at low and high intensities. Fourteen young adults (6 men and 8 women; 27.1 ± 9.1 years) performed three sets of 16-s isometric contractions with the ankle dorsiflexor muscles at 10, 30, 50, and 70 % of maximal voluntary contraction (MVC). Percent signal changes (PSCs, %) of the blood oxygenation level-dependent response were extracted for each contraction using region of interest analysis. Mean PSC increased with contraction intensity in the contralateral primary motor area (M1), supplementary motor area, putamen, pallidum cingulate cortex, and ipsilateral cerebellum (p < 0.05). The amplitude of force fluctuations (standard deviation, SD) increased from 10 to 70 % MVC but relative to the mean force (coefficient of variation, CV %) was greatest at 10 % MVC. The CV of force was associated with PSC in the ipsilateral parietal lobule (r = -0.28), putamen (r = -0.29), insula (r = -0.33), and contralateral superior frontal gyrus (r = -0.33, p < 0.05). There were minimal sex differences in brain activation across the isometric motor tasks indicating men and women were similarly motivated and able to activate cortical motor centers during static tasks. Control of steady lower limb contractions involves cortical and subcortical motor areas in both men and women and provides insight into key areas for potential cortical plasticity with impaired or enhanced leg function.

  20. Tinnitus: Is This What Happens When the Brain's Gatekeeper Breaks Down?

    MedlinePlus

    ... 2011 Tinnitus: Is this what happens when the brain's gatekeeper breaks down? March 16, 2011 Why some ... that the limbic system—a linked network of brain structures involved in emotion, behavior, and long-term ...

  1. Activated and deactivated functional brain areas in the Deqi state: A functional MRI study.

    PubMed

    Huang, Yong; Zeng, Tongjun; Zhang, Guifeng; Li, Ganlong; Lu, Na; Lai, Xinsheng; Lu, Yangjia; Chen, Jiarong

    2012-10-25

    We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects during acupuncture. Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, thalamus and red nucleus. True needling also deactivated Brodmann areas 1, 2, 3, 4, 5, 6, 7, 9, 10, 18, 24, 31, 40 and 46.

  2. Daily variations in concentration of vasoactive intestinal polypeptide immunoreactivity in discrete brain areas of the rat.

    PubMed

    Morin, A; Denoroy, L; Jouvet, M

    1991-01-04

    The concentration of VIP-like immunoreactivity (VIP-LI) was determined by radioimmunoassay at various times of the day in 11 discrete brain areas and in the antehypophysis of rats maintained on a regular 12 h/12 h light-dark cycle. In the suprachiasmatic and periventricular nuclei the VIP-LI increased during the dark period and decreased during the subsequent light period. In addition, the VIP-LI exhibited complex variations in the locus coeruleus, the periaqueductal gray matter and the paraventricular nucleus, but did not change in the other areas investigated.

  3. REM sleep loss associated changes in orexin-A levels in discrete brain areas in rats.

    PubMed

    Mehta, Rachna; Khanday, Mudasir Ahmad; Mallick, Birendra Nath

    2015-03-17

    Rapid eye movement sleep (REMS) serves house-keeping function of the brain and its loss affects several pathophysiological processes. Relative levels of neurotransmitters including orexin A (Orx-A) in various parts of the brain in health and diseases are among the key factors for modulation of behaviors, including REMS. The level of neurotransmitter in an area in the brain directly depends on number of projecting neurons and their firing rates. The locus coeruleus (LC), the site of REM-OFF neurons, receives densest, while the pedunculo-pontine area (PPT), the site of REM-ON neurons receives lesser projections from the Orx-ergic neurons. Further, the Orx-ergic neurons are active during waking and silent during REMS and NREMS. Therefore, the level of Orx-A in discrete regions of the brain is likely to be different during normal and altered states, which in turn is likely to be responsible for altered behaviors in health and diseases, including in relation to REMS. Therefore, in the present study, we estimated Orx-A level in LC, cortex, posterior hypothalamus (PH), hippocampus, and PPT after 96 h REMSD, in post-deprivation recovered rats and in control rats. This is the first report of estimation of Orx-A in different brain regions after prolonged REMSD. It was observed that after REMSD the Orx-A level increased significantly in LC, cortex and PH which returned to normal level after recovery; however, the level did not change in the hippocampus and PPT. The Orx-A induced modulation of REMS could be secondary to increased waking.

  4. Investigating Causality Between Interacting Brain Areas with Multivariate Autoregressive Models of MEG Sensor Data

    PubMed Central

    Michalareas, George; Schoffelen, Jan-Mathijs; Paterson, Gavin; Gross, Joachim

    2013-01-01

    Abstract In this work, we investigate the feasibility to estimating causal interactions between brain regions based on multivariate autoregressive models (MAR models) fitted to magnetoencephalographic (MEG) sensor measurements. We first demonstrate the theoretical feasibility of estimating source level causal interactions after projection of the sensor-level model coefficients onto the locations of the neural sources. Next, we show with simulated MEG data that causality, as measured by partial directed coherence (PDC), can be correctly reconstructed if the locations of the interacting brain areas are known. We further demonstrate, if a very large number of brain voxels is considered as potential activation sources, that PDC as a measure to reconstruct causal interactions is less accurate. In such case the MAR model coefficients alone contain meaningful causality information. The proposed method overcomes the problems of model nonrobustness and large computation times encountered during causality analysis by existing methods. These methods first project MEG sensor time-series onto a large number of brain locations after which the MAR model is built on this large number of source-level time-series. Instead, through this work, we demonstrate that by building the MAR model on the sensor-level and then projecting only the MAR coefficients in source space, the true casual pathways are recovered even when a very large number of locations are considered as sources. The main contribution of this work is that by this methodology entire brain causality maps can be efficiently derived without any a priori selection of regions of interest. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc. PMID:22328419

  5. [Limbic ictus as a condition for anxiety attacks].

    PubMed

    Gallinat, J; Hegerl, U

    1999-03-01

    Episodes of anxiety have been reported to be the most common psychological symptoms in patients with partial seizures. They may occur before, during and after seizures and can also appear in isolation without any convulsive symptoms. The epileptic anxiety syndrome is strikingly similar to panic attacks, and panic disorder is an important differential diagnosis. The close relationship between epileptic seizures and panic attacks is of special interest for a better pathophysiological understanding of panic attacks. In the literature an epileptiform neuronal activity is discussed as a possible underlying mechanism for panic disorder. The finding that anxiety was the most common experiential phenomenon produced by electrical stimulation of amygdala and hippocampus with depth electrodes points in this direction. PET has demonstrated abnormalities of hippocampal structures during the nonpanic state of patients with panic disorder. In addition, some EEG studies have demonstrated a high incidence of epileptiform EEG patterns in patients with panic disorder with or without agoraphobia. This was the reason why several investigators proposed that a subset of panic attacks may be related to abnormal epileptiform neuronal activity in the limbic system. The size of this subset is difficult to determine because discharges in the depth of the limbic system often cannot be seen in the scalp EEG. Concerning the hypothetical pathophysiological mechanism of panic disorder therapeutic measures were taken with antiepileptic agents. The best results were obtained for valproic acid. It seems to be reasonable to make a therapeutic trial with antiepileptic medication after nonresponse to standard pharmacotherapy.

  6. Contribution of limbic norepinephrine to cannabinoid-induced aversion.

    PubMed

    Carvalho, Ana Franky; Reyes, Arith-Ruth S; Sterling, Robert C; Unterwald, Ellen; Van Bockstaele, Elisabeth J

    2010-09-01

    The cannabinoid system has risen to the forefront in the development of novel treatments for a number of pathophysiological processes. However, significant side effects have been observed in clinical trials raising concerns regarding the potential clinical utility of cannabinoid-based agents. Understanding the neural circuits and neurochemical substrates impacted by cannabinoids will provide a better means of gaging their actions within the central nervous system that may contribute to the expression of unwanted side effects. In the present study, we investigated whether norepinephrine (NE) in the limbic forebrain is a critical determinant of cannabinoid receptor agonist-induced aversion and anxiety in rats. An immunotoxin lesion approach was combined with behavioral analysis using a place conditioning paradigm and the elevated zero maze. Our results show that the non-selective CB1/CB2 receptor agonist, WIN 55,212-2, produced a significant place aversion in rats. Further, NE in the nucleus accumbens was critical for WIN 55,212-2-induced aversion but did not affect anxiety-like behaviors. Depletion of NE from the bed nucleus of the stria terminalis was ineffective in altering WIN 55,212-2-induced aversion and anxiety. These results indicate that limbic, specifically accumbal, NE is required for cannabinoid-induced aversion but is not essential to cannabinoid-induced anxiety.

  7. Connectivity reveals relationship of brain areas for reward-guided learning and decision making in human and monkey frontal cortex

    PubMed Central

    Neubert, Franz-Xaver; Mars, Rogier B.; Sallet, Jérôme; Rushworth, Matthew F. S.

    2015-01-01

    Reward-guided decision-making depends on a network of brain regions. Among these are the orbitofrontal and the anterior cingulate cortex. However, it is difficult to ascertain if these areas constitute anatomical and functional unities, and how these areas correspond between monkeys and humans. To address these questions we looked at connectivity profiles of these areas using resting-state functional MRI in 38 humans and 25 macaque monkeys. We sought brain regions in the macaque that resembled 10 human areas identified with decision making and brain regions in the human that resembled six macaque areas identified with decision making. We also used diffusion-weighted MRI to delineate key human orbital and medial frontal brain regions. We identified 21 different regions, many of which could be linked to particular aspects of reward-guided learning, valuation, and decision making, and in many cases we identified areas in the macaque with similar coupling profiles. PMID:25947150

  8. Sustained attention to spontaneous thumb sensations activates brain somatosensory and other proprioceptive areas.

    PubMed

    Bauer, Clemens C C; Díaz, José-Luis; Concha, Luis; Barrios, Fernando A

    2014-06-01

    The present experiment was designed to test if sustained attention directed to the spontaneous sensations of the right or left thumb in the absence of any external stimuli is able to activate corresponding somatosensory brain areas. After verifying in 34 healthy volunteers that external touch stimuli to either thumb effectively activate brain contralateral somatosensory areas, and after subtracting attention mechanisms employed in both touch and spontaneous-sensation conditions, fMRI evidence was obtained that the primary somatosensory cortex (specifically left BA 3a/3b) becomes active when an individual is required to attend to the spontaneous sensations of either thumb in the absence of external stimuli. In addition, the left superior parietal cortex, anterior cingulate gyrus, insula, motor and premotor cortex, left dorsolateral prefrontal cortex, Broca's area, and occipital cortices were activated. Moreover, attention to spontaneous-sensations revealed an increased connectivity between BA 3a/3b, superior frontal gyrus (BA 9) and anterior cingulate cortex (BA 32), probably allowing top-down activations of primary somatosensory cortex. We conclude that specific primary somatosensory areas in conjunction with other left parieto-frontal areas are involved in processing proprioceptive and interoceptive bodily information that underlies own body-representations and that these networks and cognitive functions can be modulated by top-down attentional processes.

  9. Defining Face Perception Areas in the Human Brain: A Large-Scale Factorial fMRI Face Localizer Analysis

    ERIC Educational Resources Information Center

    Rossion, Bruno; Hanseeuw, Bernard; Dricot, Laurence

    2012-01-01

    A number of human brain areas showing a larger response to faces than to objects from different categories, or to scrambled faces, have been identified in neuroimaging studies. Depending on the statistical criteria used, the set of areas can be overextended or minimized, both at the local (size of areas) and global (number of areas) levels. Here…

  10. Defining Face Perception Areas in the Human Brain: A Large-Scale Factorial fMRI Face Localizer Analysis

    ERIC Educational Resources Information Center

    Rossion, Bruno; Hanseeuw, Bernard; Dricot, Laurence

    2012-01-01

    A number of human brain areas showing a larger response to faces than to objects from different categories, or to scrambled faces, have been identified in neuroimaging studies. Depending on the statistical criteria used, the set of areas can be overextended or minimized, both at the local (size of areas) and global (number of areas) levels. Here…

  11. Increased activity of frontal and limbic regions to emotional stimuli in children at-risk for anxiety disorders.

    PubMed

    Christensen, Rhandi; Van Ameringen, Michael; Hall, Geoffrey

    2015-07-30

    Neuroimaging studies of children with anxiety disorders are limited, and no study has examined children who are at increased risk for developing anxiety disorders based on parental anxiety. The objective of this study was to examine the function of frontal and limbic brain regions using functional magnetic resonance imaging (fMRI) in children at risk for anxiety disorders. Study participants included high-risk children (n=20) who had at least one parent with a primary diagnosis of social anxiety disorder and normal-risk control children (n=19). Using fMRI, we measured the blood oxygenation level dependent response while high-risk and normal-risk children were exposed to different emotional facial stimuli. We found greater activation of frontal, temporal and limbic regions in high-risk children relative to normal-risk children during the presentation of emotional stimuli (angry and happy). These regions included the prefrontal cortex, anterior cingulate, hippocampus and insula. Our within-group analysis revealed similar patterns of hyperactivity in high-risk children with and without current anxiety symptoms. To our knowledge, this is the first study to demonstrate functional alterations in emotion-processing brain regions in children who are at risk for anxiety disorders based on parental anxiety. These findings are consistent with previous fMRI studies of pediatric anxiety and behaviorally inhibited children, and they contribute to our understanding of the neural correlates of risk for anxiety disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. [Surgical treatment of eloquent brain area tumors using neurophysiological mapping of the speech and motor areas and conduction tracts].

    PubMed

    Zuev, A A; Korotchenko, E N; Ivanova, D S; Pedyash, N V; Teplykh, B A

    To evaluate the efficacy of intraoperative neurophysiological mapping in removing eloquent brain area tumors (EBATs). Sixty five EBAT patients underwent surgical treatment using intraoperative neurophysiological mapping at the Pirogov National Medical and Surgical Center in the period from 2014 to 2015. On primary neurological examination, 46 (71%) patients were detected with motor deficits of varying severity. Speech disorders were diagnosed in 17 (26%) patients. Sixteen patients with concomitant or isolated lesions of the speech centers underwent awake surgery using the asleep-awake-asleep protocol. Standard neurophysiological monitoring included transcranial stimulation as well as motor and, if necessary, speech mapping. The motor and speech areas were mapped with allowance for the preoperative planning data (obtained with a navigation station) synchronized with functional MRI. In this case, a broader representation of the motor and speech centers was revealed in 12 (19%) patients. During speech mapping, no speech disorders were detected in 7 patients; in 9 patients, stimulation of the cerebral cortex in the intended surgical area induced motor (3 patients), sensory (4), and amnesic (2) aphasia. In the total group, we identified 11 patients in whom the tumor was located near the internal capsule. Upon mapping of the conduction tracts in the internal capsule area, the stimulus strength during tumor resection was gradually decreased from 10 mA to 5 mA. Tumor resection was stopped when responses retained at a stimulus strength of 5 mA, which, when compared to the navigation data, corresponded to a distance of about 5 mm to the internal capsule. Completeness of tumor resection was evaluated (contrast-enhanced MRI) in all patients on the first postoperative day. According to the control MRI data, the tumor was resected totally in 60% of patients, subtotally in 24% of patients, and partially in 16% of patients. In the early postoperative period, the development or

  13. [Functional imaging of deep brain stimulation in idiopathic Parkinson's disease].

    PubMed

    Hilker, R

    2010-10-01

    Functional brain imaging allows the effects of deep brain stimulation (DBS) on the living human brain to be investigated. In patients with advanced Parkinson's disease (PD), positron emission tomography (PET) studies were undertaken at rest as well as under motor, cognitive or behavioral activation. DBS leads to a reduction of abnormal PD-related network activity in the motor system, which partly correlates with the improvement of motor symptoms. The local increase of energy consumption within the direct target area suggests a predominant excitatory influence of the stimulation current on neuronal tissue. Remote effects of DBS of the subthalamic nucleus (STN) on frontal association cortices indicate an interference of stimulation energy with associative and limbic basal ganglia loops. Taken together, functional brain imaging provides very valuable data for advancement of the DBS technique in PD therapy.

  14. Measuring and comparing brain cortical surface area and other areal quantities

    PubMed Central

    Winkler, Anderson M.; Sabuncu, Mert R.; Yeo, B.T. Thomas; Fischl, Bruce; Greve, Douglas N.; Kochunov, Peter; Nichols, Thomas E.; Blangero, John; Glahn, David C.

    2012-01-01

    Structural analysis of MRI data on the cortical surface usually focuses on cortical thickness. Cortical surface area, when considered, has been measured only over gross regions or approached indirectly via comparisons with a standard brain. Here we demonstrate that direct measurement and comparison of the surface area of the cerebral cortex at a fine scale is possible using mass conservative interpolation methods. We present a framework for analyses of the cortical surface area, as well as for any other measurement distributed across the cortex that is areal by nature. The method consists of the construction of a mesh representation of the ortex, registration to a common coordinate system and, crucially, interpolation using a pycnophylactic method. Statistical analysis of surface area is done with power-transformed data to address lognormality, and inference is done with permutation methods. We introduce the concept of facewise analysis, discuss its interpretation and potential applications. PMID:22446492

  15. Regional Brain Differences in Cortical Thickness, Surface Area and Subcortical Volume in Individuals with Williams Syndrome

    PubMed Central

    Meda, Shashwath A.; Pryweller, Jennifer R.; Thornton-Wells, Tricia A.

    2012-01-01

    Williams syndrome (WS) is a rare genetic neurodevelopmental disorder characterized by increased non-social anxiety, sensitivity to sounds and hypersociability. Previous studies have reported contradictory findings with regard to regional brain variation in WS, relying on only one type of morphological measure (usually volume) in each study. The present study aims to contribute to this body of literature and perhaps elucidate some of these discrepancies by examining concurrent measures of cortical thickness, surface area and subcortical volume between WS subjects and typically-developing (TD) controls. High resolution MRI scans were obtained on 31 WS subjects and 50 typically developing control subjects. We derived quantitative regional estimates of cortical thickness, cortical surface area, and subcortical volume using FreeSurfer software. We evaluated between-group ROI differences while controlling for total intracranial volume. In post-hoc exploratory analyses within the WS group, we tested for correlations between regional brain variation and Beck Anxiety Inventory scores. Consistent with our hypothesis, we detected complex patterns of between-group cortical variation, which included lower surface area in combination with greater thickness in the following cortical regions: post central gyrus, cuneus, lateral orbitofrontal cortex and lingual gyrus. Additional cortical regions showed between-group differences in one (but not both) morphological measures. Subcortical volume was lower in the basal ganglia and the hippocampus in WS versus TD controls. Exploratory correlations revealed that anxiety scores were negatively correlated with gray matter surface area in insula, OFC, rostral middle frontal, superior temporal and lingual gyrus. Our results were consistent with previous reports showing structural alterations in regions supporting the socio-affective and visuospatial impairments in WS. However, we also were able to effectively capture novel and complex

  16. Regional brain differences in cortical thickness, surface area and subcortical volume in individuals with Williams syndrome.

    PubMed

    Meda, Shashwath A; Pryweller, Jennifer R; Thornton-Wells, Tricia A

    2012-01-01

    Williams syndrome (WS) is a rare genetic neurodevelopmental disorder characterized by increased non-social anxiety, sensitivity to sounds and hypersociability. Previous studies have reported contradictory findings with regard to regional brain variation in WS, relying on only one type of morphological measure (usually volume) in each study. The present study aims to contribute to this body of literature and perhaps elucidate some of these discrepancies by examining concurrent measures of cortical thickness, surface area and subcortical volume between WS subjects and typically-developing (TD) controls. High resolution MRI scans were obtained on 31 WS subjects and 50 typically developing control subjects. We derived quantitative regional estimates of cortical thickness, cortical surface area, and subcortical volume using FreeSurfer software. We evaluated between-group ROI differences while controlling for total intracranial volume. In post-hoc exploratory analyses within the WS group, we tested for correlations between regional brain variation and Beck Anxiety Inventory scores. Consistent with our hypothesis, we detected complex patterns of between-group cortical variation, which included lower surface area in combination with greater thickness in the following cortical regions: post central gyrus, cuneus, lateral orbitofrontal cortex and lingual gyrus. Additional cortical regions showed between-group differences in one (but not both) morphological measures. Subcortical volume was lower in the basal ganglia and the hippocampus in WS versus TD controls. Exploratory correlations revealed that anxiety scores were negatively correlated with gray matter surface area in insula, OFC, rostral middle frontal, superior temporal and lingual gyrus. Our results were consistent with previous reports showing structural alterations in regions supporting the socio-affective and visuospatial impairments in WS. However, we also were able to effectively capture novel and complex

  17. Musical structure is processed in "language" areas of the brain: a possible role for Brodmann Area 47 in temporal coherence.

    PubMed

    Levitin, Daniel J; Menon, Vinod

    2003-12-01

    The neuroanatomical correlates of musical structure were investigated using functional magnetic neuroimaging (fMRI) and a unique stimulus manipulation involving scrambled music. The experiment compared brain responses while participants listened to classical music and scrambled versions of that same music. Specifically, the scrambled versions disrupted musical structure while holding low-level musical attributes constant, including the psychoacoustic features of the music such as pitch, loudness, and timbre. Comparing music to its scrambled counterpart, we found focal activation in the pars orbitalis region (Brodmann Area 47) of the left inferior frontal cortex, a region that has been previously closely associated with the processing of linguistic structure in spoken and signed language, and its right hemisphere homologue. We speculate that this particular region of inferior frontal cortex may be more generally responsible for processing fine-structured stimuli that evolve over time, not merely those that are linguistic.

  18. Accumulation of waterborne mercury(II) in specific areas of fish brain

    SciTech Connect

    Rouleau, C.; Borg-Neczak, K.; Gottofrey, J.; Tjaelve, H.

    1999-10-01

    The authors used whole-body autoradiography to study the distribution of {sup 203}Hg(II) in the central nervous system of brown (Salmo trutta) and rainbow (Oncorhynchus mykiss) trout. Fish were either exposed to waterborne Hg(II) for 7 and 21 d or they received an intravenous injection of the metal and were sacrificed 1 and 21 d later. Mercury did not accumulate in the brain after intravenous injection, indicating that the blood-brain barrier is impervious to Hg in plasma. In contrast, Hg was accumulated in specific areas of the grain and spinal cord following water exposure. The specificity of the accumulation sites strongly suggests that waterborne Hg was taken up by water-exposed receptor cells of sensory nerves and subsequently transferred toward the brain by axonal transport, a normal physiological process for the transport of organelles and dissolved neuronal constituents along nerve axons. Accumulation of Hg in ventral horn ganglis is probably the result of leaching of metal from blood into muscle followed by uptake in motor plates. Axonal transport allows waterborne inorganic Hg, and possibly other xenobiotics, to circumvent the blood-brain barrier. Considering the importance of complex behavior in the life of fish, and the well-known deleterious effects of mercury on the nervous system, the toxicological significance of this uptake route needs to be assessed.

  19. 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

  20. [Anti-Hu antibody-positive paraneoplastic limbic encephalitis with acute motor sensory neuropathy resembling Guillain-Barré syndrome: a case study].

    PubMed

    Sakurai, Takeo; Wakida, Kenji; Kimura, Akio; Inuzuka, Takashi; Nishida, Hiroshi

    2015-01-01

    A 69-year-old man experienced general malaise, weight loss, amnesia, gait disturbance, and restlessness a month prior to admission. Brain MRI showed high intensity areas in the bilateral medial temporal lobes and insular cortices on FLAIR images, and therefore, he was diagnosed with limbic encephalitis. After admission, quadriplegia and respiratory failure progressed rapidly, and he needed ventilatory management. A nerve conduction study revealed low compound muscle action potential amplitude with loss of sensory nerve action potential, which indicated axonal sensorimotor neuropathy. We administered intravenous immunoglobulin and methylprednisolone pulse therapy, but he did not recover. Although no tumor was found on CT, his serum was positive for anti-Hu antibody; therefore, we diagnosed him with paraneoplastic neurological syndrome. An FDG-PET study showed accumulation at lesions on two hilar lymph nodes. Small cell lung carcinoma was detected by endobronchial ultrasound-guided transbronchial needle aspiration. Although paraneoplastic acute sensorimotor neuropathy with respiratory failure resembling Guillain-Barré syndrome is rare, identification of antibodies and servey of tumors aids accurate diagnosis.

  1. Effect of low doses of methamphetamine on rat limbic-related neurotensin systems.

    PubMed

    Alburges, Mario E; Hoonakker, Amanda J; Cordova, Nathaniel M; Robson, Christina M; McFadden, Lisa M; Martin, Amber L; Hanson, Glen R

    2015-08-01

    Administration of methamphetamine (METH) alters limbic-related (LR) neurotensin (NT) systems. Thus, through a D1-receptor mechanism, noncontingent high doses (5-15 mg kg(-1)), and likely self-administration, of METH appears to reduce NT release causing its accumulation and an elevation of NT-like immunoreactivity (NTLI) in limbic-related NT pathways. For comparison, we tested the effect of low doses of METH, that are more like those used in therapy, on NTLI in the core and shell of the nucleus accumbens (NAc and NAs), prefrontal cortex (PFC), ventral tegmental area (VTA), the lateral habenula (Hb) and basolateral amygdala (Amyg). METH at the dose of 0.25 mg kg(-1) in particular, but not 1.00 mg kg(-1), decreased NTLI concentration in all of the LR structures studied, except for the prefrontal cortex; however, these effects were rapid and brief being observed at 5 h but not at 24 h after treatment. In all of the LR areas where NTLI levels were reduced after the low dose of METH, the effect was blocked by pretreatment with either a D1 or a D2 antagonist. Thus, opposite to high doses like those associated with abuse, the therapeutic-like low-dose METH treatment induced reduction in NT tissue levels likely reflected an increase in NT release and a short-term depletion of the levels of this neuropeptide in LR structures, manifesting features comparable to the response of basal ganglia NT systems to similar low doses of METH.

  2. Mutation of Semaphorin-6A disrupts limbic and cortical connectivity and models neurodevelopmental psychopathology.

    PubMed

    Rünker, Annette E; O'Tuathaigh, Colm; Dunleavy, Mark; Morris, Derek W; Little, Graham E; Corvin, Aiden P; Gill, Michael; Henshall, David C; Waddington, John L; Mitchell, Kevin J

    2011-01-01

    Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.

  3. Spatial learning-related changes in metabolic activity of limbic structures at different posttask delays.

    PubMed

    Méndez-López, M; Méndez, M; Sampedro-Piquero, P; Arias, J L

    2013-01-01

    The aim of this study was to assess the functional contribution of brain limbic system regions at different moments after the acquisition of a short-term spatial memory task performed in the Morris water maze. Adult male Wistar rats were submitted to a matching-to-sample procedure with a hidden platform. The trials were made up of two daily identical visits to the platform, sample (swim-1) and retention (swim-2). To study oxidative metabolic activity, we applied cytochrome oxidase (COx) histochemistry. Densitometric measurements were taken at 1.5, 6, 24, and 48 hr posttask. An untrained group was added to explore the COx changes not specific to the learning process. The brain regions studied showed a different pattern of metabolic activity at different time points after the spatial memory task. Specifically, a significant increase of COx was found in the septal dentate gyrus, anteromedial thalamus, medial mammillary nucleus, and entorhinal cortex at early moments after learning. The entorhinal cortex maintained an increase of COx at later stages of the posttask period. In addition, an increase of COx activity was found in the supramammillary nucleus and the retrosplenial, perirhinal, and parietal cortices a long time after learning. These findings suggest that diencephalic and cortical regions are involved in this spatial learning and contribute at different moments to process this information.

  4. Visualizing an emotional valence map in the limbic forebrain by TAI-FISH.

    PubMed

    Xiu, Jianbo; Zhang, Qi; Zhou, Tao; Zhou, Ting-ting; Chen, Yang; Hu, Hailan

    2014-11-01

    A fundamental problem in neuroscience is how emotional valences are represented in the brain. We know little about how appetitive and aversive systems interact and the extent to which information regarding these two opposite values segregate and converge. Here we used a new method, tyramide-amplified immunohistochemistry-fluorescence in situ hybridization, to simultaneously visualize the neural correlates of two stimuli of contrasting emotional valence across the limbic forebrain at single-cell resolution. We discovered characteristic patterns of interaction, segregated, convergent and intermingled, between the appetitive and aversive neural ensembles in mice. In nucleus accumbens, we identified a mosaic activation pattern by positive and negative emotional cues, and unraveled previously unappreciated functional heterogeneity in the D1- and D2-type medium-spiny neurons, which correspond to the Go and NoGo pathways. These results provide insights into the coding of emotional valence in the brain and act as a proof of principle of a powerful methodology for simultaneous functional mapping of two distinct behaviors.

  5. Separate and overlapping brain areas encode subjective value during delay and effort discounting.

    PubMed

    Massar, Stijn A A; Libedinsky, Camilo; Weiyan, Chee; Huettel, Scott A; Chee, Michael W L

    2015-10-15

    Making decisions about rewards that involve delay or effort requires the integration of value and cost information. The brain areas recruited in this integration have been well characterized for delay discounting. However only a few studies have investigated how effort costs are integrated into value signals to eventually determine choice. In contrast to previous studies that have evaluated fMRI signals related to physical effort, we used a task that focused on cognitive effort. Participants discounted the value of delayed and effortful rewards. The value of cognitively effortful rewards was represented in the anterior portion of the inferior frontal gyrus and dorsolateral prefrontal cortex. Additionally, the value of the chosen option was encoded in the anterior cingulate cortex, caudate, and cerebellum. While most brain regions showed no significant dissociation between effort discounting and delay discounting, the ACC was significantly more activated in effort compared to delay discounting tasks. Finally, overlapping regions within the right orbitofrontal cortex and lateral temporal and parietal cortices encoded the value of the chosen option during both delay and effort discounting tasks. These results indicate that encoding of rewards discounted by cognitive effort and delay involves partially dissociable brain areas, but a common representation of chosen value is present in the orbitofrontal, temporal and parietal cortices.

  6. Brain functional network changes following Prelimbic area inactivation in a spatial memory extinction task.

    PubMed

    Méndez-Couz, Marta; Conejo, Nélida M; Vallejo, Guillermo; Arias, Jorge L

    2015-01-01

    Several studies suggest a prefrontal cortex involvement during the acquisition and consolidation of spatial memory, suggesting an active modulating role at late stages of acquisition processes. Recently, we have reported that the prelimbic and infralimbic areas of the prefrontal cortex, among other structures, are also specifically involved in the late phases of spatial memory extinction. This study aimed to evaluate whether the inactivation of the prelimbic area of the prefrontal cortex impaired spatial memory extinction. For this purpose, male Wistar rats were implanted bilaterally with cannulae into the prelimbic region of the prefrontal cortex. Animals were trained during 5 consecutive days in a hidden platform task and tested for reference spatial memory immediately after the last training session. One day after completing the training task, bilateral infusion of the GABAA receptor agonist Muscimol was performed before the extinction protocol was carried out. Additionally, cytochrome c oxidase histochemistry was applied to map the metabolic brain activity related to the spatial memory extinction under prelimbic cortex inactivation. Results show that animals acquired the reference memory task in the water maze, and the extinction task was successfully completed without significant impairment. However, analysis of the functional brain networks involved by cytochrome oxidase activity interregional correlations showed changes in brain networks between the group treated with Muscimol as compared to the saline-treated group, supporting the involvement of the mammillary bodies at a the late stage in the memory extinction process.

  7. Brain activation induced by psychological stress in patients with schizophrenia.

    PubMed

    Castro, M N; Villarreal, M F; Bolotinsky, N; Papávero, E; Goldschmidt, M G; Costanzo, E Y; Drucaroff, L; Wainsztein, A; de Achával, D; Pahissa, J; Bär, K-J; Nemeroff, C B; Guinjoan, S M

    2015-10-01

    Environmental influences are critical for the expression of genes putatively related to the behavioral and cognitive phenotypes of schizophrenia. Among such factors, psychosocial stress has been proposed to play a major role in the expression of symptoms. However, it is unsettled how stress interacts with pathophysiological pathways to produce the disease. We studied 21 patients with schizophrenia and 21 healthy controls aged 18 to 50years with 3T-fMRI, in which a period of 6min of resting state acquisition was followed by a block design, with three blocks of 1-min control-task, 1-min stress-task and 1-min rest after-task. Self-report of stress and PANSS were measured. Limbic structures were activated in schizophrenia patients by simple tasks and remained active during, and shortly after stress. In controls, stress-related brain activation was more time-focused, and restricted to the stressful task itself. Negative symptom severity was inversely related to activation of anterior cingulum and orbitofrontal cortex. Results might represent the neurobiological aspect of hyper-reactivity to normal stressful situations previously described in schizophrenia, thus providing evidence on the involvement of limbic areas in the response to stress in schizophrenia. Patients present a pattern of persistent limbic activation probably contributing to hypervigilance and subsequent psychotic thought distortions. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Stress shifts brain activation towards ventral 'affective' areas during emotional distraction.

    PubMed

    Oei, Nicole Y L; Veer, Ilya M; Wolf, Oliver T; Spinhoven, Philip; Rombouts, Serge A R B; Elzinga, Bernet M

    2012-04-01

    Acute stress has been shown to impair working memory (WM), and to decrease prefrontal activation during WM in healthy humans. Stress also enhances amygdala responses towards emotional stimuli. Stress might thus be specifically detrimental to WM when one is distracted by emotional stimuli. Usually, emotional stimuli presented as distracters in a WM task slow down performance, while evoking more activation in ventral 'affective' brain areas, and a relative deactivation in dorsal 'executive' areas. We hypothesized that after acute social stress, this reciprocal dorsal-ventral pattern would be shifted towards greater increase of ventral 'affective' activation during emotional distraction, while impairing WM performance. To investigate this, 34 healthy men, randomly assigned to a social stress or control condition, performed a Sternberg WM task with emotional and neutral distracters inside an MRI scanner. Results showed that WM performance after stress tended to be slower during emotional distraction. Brain activations during emotional distraction was enhanced in ventral affective areas, while dorsal executive areas tended to show less deactivation after stress. These results suggest that acute stress shifts priority towards processing of emotionally significant stimuli, at the cost of WM performance.

  9. Connectivity profiles reveal the relationship between brain areas for social cognition in human and monkey temporoparietal cortex

    PubMed Central

    Mars, Rogier B.; Sallet, Jérôme; Neubert, Franz-Xaver; Rushworth, Matthew F. S.

    2013-01-01

    The human ability to infer the thoughts and beliefs of others, often referred to as “theory of mind,” as well as the predisposition to even consider others, are associated with activity in the temporoparietal junction (TPJ) area. Unlike the case of most human brain areas, we have little sense of whether or how TPJ is related to brain areas in other nonhuman primates. It is not possible to address this question by looking for similar task-related activations in nonhuman primates because there is no evidence that nonhuman primates engage in theory-of-mind tasks in the same manner as humans. Here, instead, we explore the relationship by searching for areas in the macaque brain that interact with other macaque brain regions in the same manner as human TPJ interacts with other human brain regions. In other words, we look for brain regions with similar positions within a distributed neural circuit in the two species. We exploited the fact that human TPJ has a unique functional connectivity profile with cortical areas with known homologs in the macaque. For each voxel in the macaque temporal and parietal cortex we evaluated the similarity of its functional connectivity profile to that of human TPJ. We found that areas in the middle part of the superior temporal cortex, often associated with the processing of faces and other social stimuli, have the most similar connectivity profile. These results suggest that macaque face processing areas and human mentalizing areas might have a similar precursor. PMID:23754406

  10. Connectivity profiles reveal the relationship between brain areas for social cognition in human and monkey temporoparietal cortex.

    PubMed

    Mars, Rogier B; Sallet, Jérôme; Neubert, Franz-Xaver; Rushworth, Matthew F S

    2013-06-25

    The human ability to infer the thoughts and beliefs of others, often referred to as "theory of mind," as well as the predisposition to even consider others, are associated with activity in the temporoparietal junction (TPJ) area. Unlike the case of most human brain areas, we have little sense of whether or how TPJ is related to brain areas in other nonhuman primates. It is not possible to address this question by looking for similar task-related activations in nonhuman primates because there is no evidence that nonhuman primates engage in theory-of-mind tasks in the same manner as humans. Here, instead, we explore the relationship by searching for areas in the macaque brain that interact with other macaque brain regions in the same manner as human TPJ interacts with other human brain regions. In other words, we look for brain regions with similar positions within a distributed neural circuit in the two species. We exploited the fact that human TPJ has a unique functional connectivity profile with cortical areas with known homologs in the macaque. For each voxel in the macaque temporal and parietal cortex we evaluated the similarity of its functional connectivity profile to that of human TPJ. We found that areas in the middle part of the superior temporal cortex, often associated with the processing of faces and other social stimuli, have the most similar connectivity profile. These results suggest that macaque face processing areas and human mentalizing areas might have a similar precursor.

  11. Investigating causality between interacting brain areas with multivariate autoregressive models of MEG sensor data.

    PubMed

    Michalareas, George; Schoffelen, Jan-Mathijs; Paterson, Gavin; Gross, Joachim

    2013-04-01

    In this work, we investigate the feasibility to estimating causal interactions between brain regions based on multivariate autoregressive models (MAR models) fitted to magnetoencephalographic (MEG) sensor measurements. We first demonstrate the theoretical feasibility of estimating source level causal interactions after projection of the sensor-level model coefficients onto the locations of the neural sources. Next, we show with simulated MEG data that causality, as measured by partial directed coherence (PDC), can be correctly reconstructed if the locations of the interacting brain areas are known. We further demonstrate, if a very large number of brain voxels is considered as potential activation sources, that PDC as a measure to reconstruct causal interactions is less accurate. In such case the MAR model coefficients alone contain meaningful causality information. The proposed method overcomes the problems of model nonrobustness and large computation times encountered during causality analysis by existing methods. These methods first project MEG sensor time-series onto a large number of brain locations after which the MAR model is built on this large number of source-level time-series. Instead, through this work, we demonstrate that by building the MAR model on the sensor-level and then projecting only the MAR coefficients in source space, the true casual pathways are recovered even when a very large number of locations are considered as sources. The main contribution of this work is that by this methodology entire brain causality maps can be efficiently derived without any a priori selection of regions of interest. Copyright © 2011 Wiley Periodicals, Inc.

  12. Prenatal stress alters the negative correlation between neuronal activation in limbic regions and behavioral responses in rats exposed to high and low anxiogenic environments.

    PubMed

    Mairesse, Jérôme; Viltart, Odile; Salomé, Nicolas; Giuliani, Alessandro; Catalani, Assia; Casolini, Paola; Morley-Fletcher, Sara; Nicoletti, Ferdinando; Maccari, Stefania

    2007-08-01

    Behavioral adaptation to an anxiogenic environment involves the activity of various interconnected limbic regions, such as the amygdala, hippocampus and prefrontal cortex. Prenatal stress (PS) in rats affects the ability to cope with environmental challenges and alters brain plasticity, leading to long-lasting behavioral and neurobiological alterations. We examined in PS and control animals whether behavioral reactivity was correlated to neuronal activation by assessing Fos protein expression in limbic regions of rats exposed to a low or high anxiogenic environment (the closed and open arms of an elevated plus maze, respectively). A negative correlation was found between behavioral and neuronal activation, with a lower behavioral reactivity and a higher neuronal response observed in rats exposed to the more anxiogenic environment (the open arm) with respect to the less anxiogenic environment (the closed arm). Interestingly, the variation in the neurobehavioral response between the two arms of the maze was less pronounced in rats that had been subjected to PS. This study provides a remarkable example of how long-lasting changes in brain plasticity induced by PS affect the ability of limbic neurons to cope with anxiogenic stimuli of different strength.

  13. Corpus Callosum Area and Brain Volume in Autism Spectrum Disorder: Quantitative Analysis of Structural MRI from the ABIDE Database

    ERIC Educational Resources Information Center

    Kucharsky Hiess, R.; Alter, R.; Sojoudi, S.; Ardekani, B. A.; Kuzniecky, R.; Pardoe, H. R.

    2015-01-01

    Reduced corpus callosum area and increased brain volume are two commonly reported findings in autism spectrum disorder (ASD). We investigated these two correlates in ASD and healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE). Automated methods were used to segment the corpus callosum and intracranial…

  14. Corpus Callosum Area and Brain Volume in Autism Spectrum Disorder: Quantitative Analysis of Structural MRI from the ABIDE Database

    ERIC Educational Resources Information Center

    Kucharsky Hiess, R.; Alter, R.; Sojoudi, S.; Ardekani, B. A.; Kuzniecky, R.; Pardoe, H. R.

    2015-01-01

    Reduced corpus callosum area and increased brain volume are two commonly reported findings in autism spectrum disorder (ASD). We investigated these two correlates in ASD and healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE). Automated methods were used to segment the corpus callosum and intracranial…

  15. Brain networks modulated by subthalamic nucleus deep brain stimulation.

    PubMed

    Accolla, Ettore A; Herrojo Ruiz, Maria; Horn, Andreas; Schneider, Gerd-Helge; Schmitz-Hübsch, Tanja; Draganski, Bogdan; Kühn, Andrea A

    2016-09-01

    Deep brain stimulation of the subthalamic nucleus is an established treatment for the motor symptoms of Parkinson's disease. Given the frequent occurrence of stimulation-induced affective and cognitive adverse effects, a better understanding about the role of the subthalamic nucleus in non-motor functions is needed. The main goal of this study is to characterize anatomical circuits modulated by subthalamic deep brain stimulation, and infer about the inner organization of the nucleus in terms of motor and non-motor areas. Given its small size and anatomical intersubject variability, functional organization of the subthalamic nucleus is difficult to investigate in vivo with current methods. Here, we used local field potential recordings obtained from 10 patients with Parkinson's disease to identify a subthalamic area with an analogous electrophysiological signature, namely a predominant beta oscillatory activity. The spatial accuracy was improved by identifying a single contact per macroelectrode for its vicinity to the electrophysiological source of the beta oscillation. We then conducted whole brain probabilistic tractography seeding from the previously identified contacts, and further described connectivity modifications along the macroelectrode's main axis. The designated subthalamic 'beta' area projected predominantly to motor and premotor cortical regions additional to connections to limbic and associative areas. More ventral subthalamic areas showed predominant connectivity to medial temporal regions including amygdala and hippocampus. We interpret our findings as evidence for the convergence of different functional circuits within subthalamic nucleus' portions deemed to be appropriate as deep brain stimulation target to treat motor symptoms in Parkinson's disease. Potential clinical implications of our study are illustrated by an index case where deep brain stimulation of estimated predominant non-motor subthalamic nucleus induced hypomanic behaviour. © The

  16. Distinct and Overlapping Brain Areas Engaged during Value-Based, Mathematical, and Emotional Decision Processing.

    PubMed

    Hsu, Chun-Wei; Goh, Joshua O S

    2016-01-01

    When comparing between the values of different choices, human beings can rely on either more cognitive processes, such as using mathematical computation, or more affective processes, such as using emotion. However, the neural correlates of how these two types of processes operate during value-based decision-making remain unclear. In this study, we investigated the extent to which neural regions engaged during value-based decision-making overlap with those engaged during mathematical and emotional processing in a within-subject manner. In a functional magnetic resonance imaging experiment, participants viewed stimuli that always consisted of numbers and emotional faces that depicted two choices. Across tasks, participants decided between the two choices based on the expected value of the numbers, a mathematical result of the numbers, or the emotional face stimuli. We found that all three tasks commonly involved various cortical areas including frontal, parietal, motor, somatosensory, and visual regions. Critically, the mathematical task shared common areas with the value but not emotion task in bilateral striatum. Although the emotion task overlapped with the value task in parietal, motor, and sensory areas, the mathematical task also evoked responses in other areas within these same cortical structures. Minimal areas were uniquely engaged for the value task apart from the other two tasks. The emotion task elicited a more expansive area of neural activity whereas value and mathematical task responses were in more focal regions. Whole-brain spatial correlation analysis showed that valuative processing engaged functional brain responses more similarly to mathematical processing than emotional processing. While decisions on expected value entail both mathematical and emotional processing regions, mathematical processes have a more prominent contribution particularly in subcortical processes.

  17. Distinct and Overlapping Brain Areas Engaged during Value-Based, Mathematical, and Emotional Decision Processing

    PubMed Central

    Hsu, Chun-Wei; Goh, Joshua O. S.

    2016-01-01

    When comparing between the values of different choices, human beings can rely on either more cognitive processes, such as using mathematical computation, or more affective processes, such as using emotion. However, the neural correlates of how these two types of processes operate during value-based decision-making remain unclear. In this study, we investigated the extent to which neural regions engaged during value-based decision-making overlap with those engaged during mathematical and emotional processing in a within-subject manner. In a functional magnetic resonance imaging experiment, participants viewed stimuli that always consisted of numbers and emotional faces that depicted two choices. Across tasks, participants decided between the two choices based on the expected value of the numbers, a mathematical result of the numbers, or the emotional face stimuli. We found that all three tasks commonly involved various cortical areas including frontal, parietal, motor, somatosensory, and visual regions. Critically, the mathematical task shared common areas with the value but not emotion task in bilateral striatum. Although the emotion task overlapped with the value task in parietal, motor, and sensory areas, the mathematical task also evoked responses in other areas within these same cortical structures. Minimal areas were uniquely engaged for the value task apart from the other two tasks. The emotion task elicited a more expansive area of neural activity whereas value and mathematical task responses were in more focal regions. Whole-brain spatial correlation analysis showed that valuative processing engaged functional brain responses more similarly to mathematical processing than emotional processing. While decisions on expected value entail both mathematical and emotional processing regions, mathematical processes have a more prominent contribution particularly in subcortical processes. PMID:27375466

  18. Cognitive and emotional modulation of brain default operation.

    PubMed

    Pallesen, Karen Johanne; Brattico, Elvira; Bailey, Christopher J; Korvenoja, Antti; Gjedde, Albert

    2009-06-01

    Goal-directed behavior lowers activity in brain areas that include the medial frontal cortex, the medial and lateral parietal cortex, and limbic and paralimbic brain regions, commonly referred to as the "default network." These activity decreases are believed to reflect the interruption of processes that are ongoing when the mind is in a restful state. Previously, the nature of these processes was probed by varying cognitive task parameters, but the presence of emotional processes, while often assumed, was little investigated. With fMRI, we studied the effect of systematic variations of both cognitive load and emotional stimulus connotation on task-related decreases in the default network by employing an auditory working memory (WM) task with musical sounds. The performance of the WM task, compared to passive listening, lowered the activity in medial and lateral, prefrontal, parietal, temporal, and limbic regions. In a subset of these regions, the magnitude of decrease depended on the memory load; the greater the cognitive load, the larger the magnitude of the observed decrease. Furthermore, in the right amygdala and the left precuneus, areas previously associated with processing of unpleasant dissonant musical sounds, there was an interaction between the experimental condition and the stimulus type. The current results are consistent with the previously reported effect of task difficulty on task-related brain activation decreases. The results also indicate that task-related decreases may be further modulated by the emotional stimulus connotation.

  19. Group independent component analysis and functional MRI examination of changes in language areas associated with brain tumors at different locations.

    PubMed

    Wang, Liya; Chen, Dandan; Yang, Xiaofeng; Olson, Jeffrey J; Gopinath, Kaundinya; Fan, Tianning; Mao, Hui

    2013-01-01

    This study investigates the effect of tumor location on alterations of language network by brain tumors at different locations using blood oxygenation level dependent (BOLD) fMRI and group independent component analysis (ICA). BOLD fMRI data were obtained from 43 right handed brain tumor patients. Presurgical mapping of language areas was performed on all 43 patients with a picture naming task. All data were retrospectively analyzed using group ICA. Patents were divided into three groups based on tumor locations, i.e., left frontal region, left temporal region or right hemisphere. Laterality index (LI) was used to assess language lateralization in each group. The results from BOLD fMRI and ICA revealed the different language activation patterns in patients with brain tumors located in different brain regions. Language areas, such as Broca's and Wernicke's areas, were intact in patients with tumors in the right hemisphere. Significant functional changes were observed in patients with tumor in the left frontal and temporal areas. More specifically, the tumors in the left frontal region affect both Broca's and Wernicke's areas, while tumors in the left temporal lobe affect mainly Wernicke's area. The compensated activation increase was observed in the right frontal areas in patients with left hemisphere tumors. Group ICA provides a model free alternative approach for mapping functional networks in brain tumor patients. Altered language activation by different tumor locations suggested reorganization of language functions in brain tumor patients and may help better understanding of the language plasticity.

  20. Use of cellular telephones and brain tumour risk in urban and rural areas

    PubMed Central

    Hardell, L; Carlberg, M; Hansson, M

    2005-01-01

    Aims: To investigate the association between the use of cellular or cordless telephones and the risk for brain tumours in different geographical areas, urban and rural. Methods: Patients aged 20–80 years, living in the middle part of Sweden, and diagnosed between 1 January 1997 and 30 June 2000 were included. One control matched for sex and age in five year age groups was selected for each case. Use of different phone types was assessed by a questionnaire. Results: The number of participating cases was 1429; there were 1470 controls. An effect of rural living was most pronounced for digital cellular telephones. Living in rural areas yielded an odds ratio (OR) of 1.4 (95% CI 0.98 to 2.0), increasing to 3.2 (95% CI 1.2 to 8.4) with >5 year latency time for digital phones. The corresponding ORs for living in urban areas were 0.9 (95% CI 0.8 to 1.2) and 0.9 (95% CI 0.6 to 1.4), respectively. This effect was most obvious for malignant brain tumours. Conclusion: In future studies, place of residence should be considered in assessment of exposure to microwaves from cellular telephones, although the results in this study must be interpreted with caution due to low numbers in some of the calculations. PMID:15901886

  1. SPECT assessment of brain activation induced by caffeine: no effect on areas involved in dependence.

    PubMed

    Nehlig, Astrid; Armspach, Jean-Paul; Namer, Izzie J

    2010-01-01

    Caffeine is not considered addictive, and in animals it does not trigger metabolic increases or dopamine release in brain areas involved in reinforcement and reward. Our objective was to measure caffeine effects on cerebral perfusion in humans using single photon emission computed tomography with a specific focus on areas of reinforcement and reward. Two groups of nonsmoking subjects were studied, one with a low (8 subjects) and one with a high (6 subjects) daily coffee consumption. The subjects ingested 3 mg/kg caffeine or placebo in a raspberry-tasting drink, and scans were performed 45 min after ingestion. A control group of 12 healthy volunteers receiving no drink was also studied. Caffeine consumption led to a generalized, statistically nonsignificant perfusion decrease of 6% to 8%, comparable in low and high consumers. Compared with controls, low consumers displayed neuronal activation bilaterally in inferior frontal gyrus-anterior insular cortex and uncus, left internal parietal cortex, right lingual gyrus, and cerebellum. In high consumers, brain activation occurred bilaterally only in hypothalamus. Thus, on a background of widespread low-amplitude perfusion decrease, caffeine activates a few regions mainly involved in the control of vigilance, anxiety, and cardiovascular regulation, but does not affect areas involved in reinforcing and reward.

  2. SPECT assessment of brain activation induced by caffeine: no effect on areas involved in dependence

    PubMed Central

    Nehlig, Astrid; Armspach, Jean-Paul; Namer, Izzie J.

    2010-01-01

    Caffeine is not considered addictive, and in animals it does not trigger metabolic increases or dopamine release in brain areas involved in reinforcement and reward. Our objective was to measure caffeine effects on cerebral perfusion in humans using single photon emission computed tomography, with a specific focus on areas of reinforcement and reward. Two groups of nonsmoking subjects were studied, one with a low (8 subjects) and one with a high (6 subjects) daily coffee consumption. The subjects ingested 3 mg/kg caffeine or placebo in a raspberry-tasting drink, and scans were performed 45 min after ingestion. A control group of 12 healthy volunteers receiving no drink was also studied. Caffeine consumption led to a generalized, statistically nonsignificant perfusion decrease of 6% to 8%, comparable in low and high consumers. Compared with controls, low consumers displayed neuronal activation bilaterally in inferior frontal gyrusanterior insular cortex and uncus, left internal parietal cortex, right lingual gyrus, and cerebellum. In high consumers, brain activation occurred bilaterally only in hypothalamus. Thus, on a background of widespread low-amplitude perfusion decrease, caffeine activates a few regions mainly involved in the control of vigilance, anxiety, and cardiovascular regulation, but does not affect areas involved in reinforcing and reward. PMID:20623930

  3. Fronto-limbic volumetric changes in major depressive disorder.

    PubMed

    Malykhin, Nikolai V; Carter, Rawle; Hegadoren, Kathleen M; Seres, Peter; Coupland, Nicholas J

    2012-02-01

    Fronto-limbic dysregulation in major depressive disorder (MDD) may be influenced by early life stress and antidepressant treatment. The present structural MRI study aimed to determine the relationship between amygdala, cingulate and subgenual prefrontal cortex volumes in MDD and their associations with child abuse and antidepressants. Right-handed subjects (21-50 years), meeting DSM-IV criteria for MDD, either with (n=19) or without (n=20) childhood sexual or physical abuse. Healthy controls (n=34) were matched for age, sex, education and smoking. 3D-MPRAGE images with a spatial resolution of 1.5 mm×1.0 mm×1.0 mm were acquired with a Siemens Sonata 1.5 T system. Volumes of subgenual prefrontal cortex, amygdala and affective, cognitive, superior and posterior divisions of cingulate cortex were analyzed using DISPLAY software using reliable volumetric protocols. Groups were compared using ANCOVA, with intracranial volume as a covariate. MDD subjects had low cingulate (cognitive division) and high amygdala volumes. Low cingulate volume was related to abuse and treatment history. Amygdala volume was predicted by subgenual prefrontal and cingulate (cognitive division) volumes and the presence of paracingulate cortex. This study was cross sectional and the sample size was limited for subgroup and correlational analyses. Our data suggest that MDD may be associated with alterations in anterior cingulate cortex and amygdala. Morphological variation, early stress and stress-protective factors may contribute to differences in fronto-limbic structures in MDD. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. [Effects of methomyl on acetylcholinesterase in erythrocyte membrane and various brain areas].

    PubMed

    Zhao, Fei; Li, Tao; Zhang, Changchun; Xu, Yiping; Xu, Hangong; Shi, Nian

    2015-06-01

    To study the toxicity of methomyl to acetylcholinesterase (AChE) in different regions. The optimal temperature and time for measurement of AChE activity were determined in vitro. The dose- and time-response relationships of methomyl with AChE activity in human erythrocyte membrane, rat erythrocyte membrane, cortical synapses, cerebellar synapses, hippocampal synapses, and striatal synapses were evaluated. The half maximal inhibitory concentration (IC50) and bimolecular rate constant (K) of methomyl for AChE activity in different regions were calculated, and the type of inhibition of AChE activity by methomyl was determined. AChE achieved the maximum activity at 370 °C, and the optimal time to determine initial reaction velocity was 0-17 min. There were dose- and time-response relationships between methomyl and AChE activity in the erythrocyte membrane and various brain areas. The IC50 value of methomyl for AChE activity in human erythrocyte membrane was higher than that in rat erythrocyte membrane, while the Ki value of methomyl for AChE activity in rat erythrocyte membrane was higher than that in human erythrocyte membrane. Among synapses in various brain areas, the striatum had the highest IC50 value, followed by the cerebellum, cerebral cortex, and hippocampus, while the cerebral cortex had the highest Ki value, followed by the hippocampus, striatum, and cerebellum. Lineweaver-Burk diagram demonstrated that with increasing concentration of methomyl, the maximum reaction velocity (Vmax) of AChE decreased, and the Michaelis constant (Km) remained the same. Methomyl is a reversible non-competitive inhibitor of AChE. AChE of rat erythrocyte membrane is more sensitive to methomyl than that of human erythrocyte membrane; the cerebral cortical synapses have the most sensitive AChE to methomyl among synapses in various brain areas.

  5. Abnormal Brain Areas Common to the Focal Epilepsies: Multivariate Pattern Analysis of fMRI.

    PubMed

    Pedersen, Mangor; Curwood, Evan K; Vaughan, David N; Omidvarnia, Amir H; Jackson, Graeme D

    2016-04-01

    Individuals with focal epilepsy have heterogeneous sites of seizure origin. However, there may be brain regions that are common to most cases of intractable focal epilepsy. In this study, we aim to identify these using multivariate analysis of task-free functional MRI. Fourteen subjects with extratemporal focal epilepsy and 14 healthy controls were included in the study. Task-free functional MRI data were used to calculate voxel-wise regional connectivity with regional homogeneity (ReHo) and weighted degree centrality (DCw), in addition to regional activity using fraction of amplitude of low-frequency fluctuations (fALFF). Multivariate pattern analysis was applied to each of these metrics to discriminate brain areas that differed between focal epilepsy subjects and healthy controls. ReHo and DCw classified focal epilepsy subjects from healthy controls with high accuracy (89.3% and 75%, respectively). However, fALFF did not significantly classify patients from controls. Increased regional network activity in epilepsy subjects was seen in the ipsilateral piriform cortex, insula, and thalamus, in addition to the dorsal anterior cingulate cortex and lateral frontal cortices. Decreased regional connectivity was observed in the ventromedial prefrontal cortex, as well as lateral temporal cortices. Patients with extratemporal focal epilepsy have common areas of abnormality (ReHo and DCw measures), including the ipsilateral piriform cortex, temporal neocortex, and ventromedial prefrontal cortex. ReHo shows additional increase in the "salience network" that includes anterior insula and anterior cingulate cortex. DCw showed additional effects in the ipsilateral thalamus and striatum. These brain areas may represent key regional network properties underlying focal epilepsy.

  6. Combining Functional Neuroimaging with Off-Line Brain Stimulation: Modulation of Task-Related Activity in Language Areas

    ERIC Educational Resources Information Center

    Andoh, Jamila; Paus, Tomas

    2011-01-01

    Repetitive TMS (rTMS) provides a noninvasive tool for modulating neural activity in the human brain. In healthy participants, rTMS applied over the language-related areas in the left hemisphere, including the left posterior temporal area of Wernicke (LTMP) and inferior frontal area of Broca, have been shown to affect performance on word…

  7. Combining Functional Neuroimaging with Off-Line Brain Stimulation: Modulation of Task-Related Activity in Language Areas

    ERIC Educational Resources Information Center

    Andoh, Jamila; Paus, Tomas

    2011-01-01

    Repetitive TMS (rTMS) provides a noninvasive tool for modulating neural activity in the human brain. In healthy participants, rTMS applied over the language-related areas in the left hemisphere, including the left posterior temporal area of Wernicke (LTMP) and inferior frontal area of Broca, have been shown to affect performance on word…

  8. Electrophysiological correlates of the limbic-motor interactions in various behavioral states in rats.

    PubMed

    Korzeniewska, A; Kasicki, S; Zagrodzka, J

    1997-08-01

    Depth electroencephalographic (EEG) activity was recorded from basolateral amygdala (BLA), ventral subiculum (VSB), n. accumbens (ACC) and subpallidal area (SPL) in freely moving rats, during locomotor tasks with various types of reinforcement in order to compare the strength of limbic-motor interactions in selected behavioral situations. For all EEG signals multichannel coherences (ordinary, multiple and partial) were calculated using autoregression model. Partial coherences indicate the level of synchronization between two signals, thus they were assumed to indicate the strength of direct connection between the structures from which these signals have been recorded. The partial coherences were calculated for six selected frequency bands and the strength of connections within the BLA-VSB-ACC-SPL circuit was estimated for two different behavioral situations and compared. It was found that the strength of connections is sensitive to changes in both motor and emotional aspects of behavioral situation: the strength of BLA-VSB, VSB-ACC, and ACC-SPL depended on motor demands of behavioral task; these of BLA-VSB increased in the highest frequency bands in all emotionally engaging situations when compared with well trained locomotive; the strength of ACC-SPL increased in situations when automatic stereotyped motor behavior was induced by biologically important stimuli, while it decreased or did not change in the motor tasks demanding more precise and quickly adjustable movements. The results are discussed according to the motor-limbic integration model of proposed by Mogenson and show the dynamics of its connections in relation to the motivational-emotional context of the task.

  9. Ventral tegmental area deep brain stimulation in refractory short-lasting unilateral neuralgiform headache attacks.

    PubMed

    Miller, Sarah; Akram, Harith; Lagrata, Susie; Hariz, Marwan; Zrinzo, Ludvic; Matharu, Manjit

    2016-10-01

    SEE LEONE AND PROIETTI CECCHINI DOI101093/AWW233 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Short-lasting unilateral neuralgiform headache attacks are primary headache disorders characterized by short-lasting attacks of unilateral pain accompanied by autonomic features. A small minority are refractory to medical treatment. Neuroimaging studies have suggested a role of the posterior hypothalamic region in their pathogenesis. Previous case reports on deep brain stimulation of this region, now understood to be the ventral tegmental area, for this disorder are limited to a total of three patients. We present a case series of 11 new patients treated with ventral tegmental area deep brain stimulation in an uncontrolled, open-label prospective observational study. Eleven patients with refractory short-lasting unilateral neuralgiform headache attacks underwent ipsilateral ventral tegmental area deep brain stimulation in a specialist unit. All patients had failed, or been denied access to, occipital nerve stimulation within the UK's National Health Service. Primary endpoint was change in mean daily attack frequency at final follow-up. Secondary outcomes included attack severity, attack duration, headache load (a composite score of attack frequency, severity and duration), quality of life measures, disability and affective scores. Information was also collected on adverse events. Eleven patients (six male) with a median age of 50 years (range 26-67) were implanted between 2009 and 2014. Median follow-up was 29 months (range 7-63). At final follow-up the median improvement in daily attack frequency was 78% (interquartile range 33%). Response rate (defined as at least a 50% improvement in daily attack frequency) was 82% and four patients were rendered pain-free for prolonged periods of time. Headache load improved by 99% (interquartile range 52%). Improvements were observed in a number of quality of life, disability and affect measures. Adverse events included mild incision

  10. Brain Activity Changes in Somatosensory and Emotion-Related Areas With Medial Patellofemoral Ligament Deficiency.

    PubMed

    Kadowaki, Masaru; Tadenuma, Taku; Kumahashi, Nobuyuki; Uchio, Yuji

    2017-08-11

    Patellar instability with medial patellofemoral ligament (MPFL) deficiency is a common sports injury among young people. Although nonoperative and surgical treatment can provide stability of the patella, patients often have anxiety related to the knee. We speculate that neural dysfunction may be related to anxiety in these patients; however, the mechanism in the brain that generates this anxiety remains unknown. (1) How does brain activity in patients with MPFL deficiency change in the areas related to somatic sensation against lateral shift of the patella? (2) How does patella instability, which can lead to continuous fear or apprehension for dislocation, influence brain activity in the areas related to emotion? Nineteen patients with MPFL deficiency underwent surgical reconstruction in our hospital from April 2012 to March 2014. Excluding seven patients with osteochondral lesions, 12 patients (five males and seven females; mean age, 20 years) with MPFL deficiency were sequentially included in this study. Eleven control subjects (four males and seven females; mean age, 23 years) were recruited from medical students who had no history of knee injury. Diagnosis of the MPFL deficiency was made with MR images, which confirmed the rupture, and by proving the instability with a custom-made biomechanical device. Brain activity during passive lateral stress to the patella was assessed by functional MRI. Functional and anatomic images were analyzed using statistical parametric mapping. Differences in functional MRI outcome measures from the detected activated brain regions between the patients with MPFL deficiency and controls were assessed using t tests. Intergroup analysis showed less activity in several sensorimotor cortical areas, including the contralateral primary somatosensory areas (% signal change for MPFL group 0.49% versus 1.1% for the control group; p < 0.001), thalamus (0.2% versus 0.41% for the MPFL versus control, respectively; p < 0.001), ipsilateral

  11. Sex hormones and brain dopamine functions.

    PubMed

    Sotomayor-Zarate, Ramon; Cruz, Gonzalo; Renard, Georgina M; Espinosa, Pedro; Ramirez, Victor D

    2014-01-01

    Sex hormones exert differential effects on a variety of sensitive tissues like the reproductive tract, gonads, liver, bone and adipose tissue, among others. In the brain, sex hormones act as neuroactive steroids regulating the function of neuroendocrine diencephalic structures like the hypothalamus. In addition, steroids can exert physiological effects upon cortical, limbic and midbrain structures, influencing different behaviors such as memory, learning, mood and reward. In the last three decades, the role of sex hormones on monoamine neurotransmitters in extra-hypothalamic areas related to motivated behaviors, learning and locomotion has been the focus of much research. The purpose of this thematic issue is to present the state of art concerning the effects of sex hormones on the neurochemical regulation of dopaminergic midbrain areas involved in neurobiological and pathological processes, such as addiction to drugs of abuse. We also discuss evidence of how neonatal exposure to sex hormones or endocrine disrupting chemicals can produce long-term changes on the neurochemical regulation of dopaminergic neurons in the limbic and midbrain areas.

  12. Control of a specific motor program by a small brain area in zebrafish

    PubMed Central

    Fajardo, Otto; Zhu, Peixin; Friedrich, Rainer W.

    2013-01-01

    Complex motor behaviors are thought to be coordinated by networks of brain nuclei that may control different elementary motor programs. Transparent zebrafish larvae offer the opportunity to analyze the functional organization of motor control networks by optical manipulations of neuronal activity during behavior. We examined motor behavior in transgenic larvae expressing channelrhodopsin-2 throughout many neurons in the brain. Wide-field optical stimulation triggered backward and rotating movements caused by the repeated execution of J-turns, a specific motor program that normally occurs during prey capture. Although optically-evoked activity was widespread, behavioral responses were highly coordinated and lateralized. 3-D mapping of behavioral responses to local optical stimuli revealed that J-turns can be triggered specifically in the anterior-ventral optic tectum (avOT) and/or the adjacent pretectum. These results suggest that the execution of J-turns is controlled by a small group of neurons in the midbrain that may act as a command center. The identification of a brain area controlling a defined motor program involved in prey capture is a step toward a comprehensive analysis of neuronal circuits mediating sensorimotor behaviors of zebrafish. PMID:23641200

  13. Areas of brain activation in males and females during viewing of erotic film excerpts.

    PubMed

    Karama, Sherif; Lecours, André Roch; Leroux, Jean-Maxime; Bourgouin, Pierre; Beaudoin, Gilles; Joubert, Sven; Beauregard, Mario

    2002-05-01

    Various lines of evidence indicate that men generally experience greater sexual arousal (SA) to erotic stimuli than women. Yet, little is known regarding the neurobiological processes underlying such a gender difference. To investigate this issue, functional magnetic resonance imaging was used to compare the neural correlates of SA in 20 male and 20 female subjects. Brain activity was measured while male and female subjects were viewing erotic film excerpts. Results showed that the level of perceived SA was significantly higher in male than in female subjects. When compared to viewing emotionally neutral film excerpts, viewing erotic film excerpts was associated, for both genders, with bilateral blood oxygen level dependent (BOLD) signal increases in the anterior cingulate, medial prefrontal, orbitofrontal, insular, and occipitotemporal cortices, as well as in the amygdala and the ventral striatum. Only for the group of male subjects was there evidence of a significant activation of the thalamus and hypothalamus, a sexually dimorphic area of the brain known to play a pivotal role in physiological arousal and sexual behavior. When directly compared between genders, hypothalamic activation was found to be significantly greater in male subjects. Furthermore, for male subjects only, the magnitude of hypothalamic activation was positively correlated with reported levels of SA. These findings reveal the existence of similarities and dissimilarities in the way the brain of both genders responds to erotic stimuli. They further suggest that the greater SA generally experienced by men, when viewing erotica, may be related to the functional gender difference found here with respect to the hypothalamus.

  14. Swim stress differentially affects limbic contents of 2-arachidonoylglycerol and 2-oleoylglycerol.

    PubMed

    Roberts, C J; Stuhr, K L; Hillard, C J

    2012-03-01

    Restraint stress exposures evoke progressively larger increases in 2-arachidonoylglycerol (2-AG) in limbic brain regions as the number of repetitions increases. The Porsolt swim test usually involves two swim exposures separated by 24 h, and we asked whether the 2-AG response differed between the first and second exposures. Four groups of male C57/Bl6N mice were studied: control; exposed to a single 6 min swim and killed immediately; exposed to a single 6 min swim and killed 24 h later; and exposed to two swims, separated by 24 h, and killed after the second swim. Outcomes were swim behavior, serum corticosterone, and 2-AG and 2-oleoylglycerol (2-OG) contents in amygdala, hippocampus, and prefrontal cortex. Mean 2-AG contents were not significantly different among the four treatment groups in any brain region and did not correlate with immobility in either forced swim exposure. However, 2-AG contents in all three brain regions only of the mice exposed to two swims were significantly, positively correlated with serum corticosterone concentrations measured at the same time. 2-OG is present in brain and exhibits a striking regional heterogeneity in control mice. 2-OG concentrations in prefrontal cortex were significantly reduced in the mice killed on the second day compared with the mice killed on the first day. As the target of 2-OG in brain is not known, the significance of these observations await further studies. Although prior exposure to swim stress does not alter brain 2-AG contents upon re-exposure, 2-AG concentrations in brain become significantly correlated with the hypothalamic-pituitary-adrenal (HPA) axis response to stress when prior exposure to the stress has occurred. These data suggest that even a single exposure to a short period of intense stress sensitizes the 2-AG response to re-exposure to that situation and are consistent with a role for endocannabinoid signaling in modulating stress responses. Copyright © 2011 IBRO. Published by Elsevier Ltd

  15. Development of Large-Scale Functional Brain Networks in Children

    PubMed Central

    Supekar, Kaustubh; Musen, Mark; Menon, Vinod

    2009-01-01

    The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7–9 y) and 22 young-adults (ages 19–22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar “small-world” organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. PMID:19621066

  16. High-resolution MEG source imaging approach to accurately localize Broca's area in patients with brain tumor or epilepsy.

    PubMed

    Huang, Charles W; Huang, Ming-Xiong; Ji, Zhengwei; Swan, Ashley Robb; Angeles, Anne Marie; Song, Tao; Huang, Jeffrey W; Lee, Roland R

    2016-05-01

    Localizing expressive language function has been challenging using the conventional magnetoencephalography (MEG) source modeling methods. The present MEG study presents a new accurate and precise approach in localizing the language areas using a high-resolution MEG source imaging method. In 32 patients with brain tumors and/or epilepsies, an object-naming task was used to evoke MEG responses. Our Fast-VESTAL source imaging method was then applied to the MEG data in order to localize the brain areas evoked by the object-naming task. The Fast-VESTAL results showed that Broca's area was accurately localized to the pars opercularis (BA 44) and/or the pars triangularis (BA 45) in all patients. Fast-VESTAL also accurately localized Wernicke's area to the posterior aspect of the superior temporal gyri in BA 22, as well as several additional brain areas. Furthermore, we found that the latency of the main peak of the response in Wernicke's area was significantly earlier than that of Broca's area. In all patients, Fast-VESTAL analysis established accurate and precise localizations of Broca's area, as well as other language areas. The responses in Wernicke's area were also shown to significantly precede those of Broca's area. The present study demonstrates that using Fast-VESTAL, MEG can serve as an accurate and reliable functional imaging tool for presurgical mapping of language functions in patients with brain tumors and/or epilepsies. Published by Elsevier Ireland Ltd.

  17. Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System.

    PubMed

    Daniele, Giuseppe; Iozzo, Patricia; Molina-Carrion, Marjorie; Lancaster, Jack; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis; Fox, Peter; Musi, Nicolas; DeFronzo, Ralph; Gastaldelli, Amalia

    2015-10-01

    Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [(18)F]2-fluoro-2-deoxy-d-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 ± 1.4 vs. 13.1 ± 1.7 μmol/min ⋅ kg) and decreased the rise in mean glucose0-60 min (107 ± 6 vs. 138 ± 8 mg/dL) and insulin0-60 min (17.3 ± 3.1 vs. 24.7 ± 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO0-60 min after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state.

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

    PubMed Central

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

    2017-01-01

    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

  19. Reading a Suspenseful Literary Text Activates Brain Areas Related to Social Cognition and Predictive Inference

    PubMed Central

    Lehne, Moritz; Engel, Philipp; Rohrmeier, Martin; Menninghaus, Winfried; Jacobs, Arthur M.; Koelsch, Stefan

    2015-01-01

    Stories can elicit powerful emotions. A key emotional response to narrative plots (e.g., novels, movies, etc.) is suspense. Suspense appears to build on basic aspects of human cognition such as processes of expectation, anticipation, and prediction. However, the neural processes underlying emotional experiences of suspense have not been previously investigated. We acquired functional magnetic resonance imaging (fMRI) data while participants read a suspenseful literary text (E.T.A. Hoffmann's “The Sandman”) subdivided into short text passages. Individual ratings of experienced suspense obtained after each text passage were found to be related to activation in the medial frontal cortex, bilateral frontal regions (along the inferior frontal sulcus), lateral premotor cortex, as well as posterior temporal and temporo-parietal areas. The results indicate that the emotional experience of suspense depends on brain areas associated with social cognition and predictive inference. PMID:25946306

  20. [Progress of clinical application of functional MRI in the localization of brain language area].

    PubMed

    Zhang, Nan; Lu, Junfeng; Wu, Jinsong

    2016-02-01

    For surgical operation in the functional area in the brain, it's commonly demanded to resect the lesion to the maximal extent on the basis of preserve the normal neural function, thus the precise localization of functional area is extremely important. As for the advantages of being widely available, easy to grasp and non-invasive, the functional MRI (fMRI) has come into wide use, while the application of language fMRI is still in the initial stage. It's important to choose appropriate fMRI task according to the individual condition of the subject, the commonly-adopted tasks include verb generation, picture naming, word recognition, word generation, etc. However, the effectiveness of using fMRI to localize language area is not totally satisfactory, adopting multiple task is an effective approach to improve the sensitivity of this technique. The application of resting state fMRI in the localization of language area and the further research of the role of fMRI in localizing the Chinese language area are the important future directions.

  1. Interaction of brain areas of visual and vestibular simultaneous activity with fMRI.

    PubMed

    Della-Justina, Hellen M; Gamba, Humberto R; Lukasova, Katerina; Nucci-da-Silva, Mariana P; Winkler, Anderson M; Amaro, Edson

    2015-01-01

    Static body equilibrium is an essential requisite for human daily life. It is known that visual and vestibular systems must work together to support equilibrium. However, the relationship between these two systems is not fully understood. In this work, we present the results of a study which identify the interaction of brain areas that are involved with concurrent visual and vestibular inputs. The visual and the vestibular systems were individually and simultaneously stimulated, using flickering checkerboard (without movement stimulus) and galvanic current, during experiments of functional magnetic resonance imaging. Twenty-four right-handed and non-symptomatic subjects participated in this study. Single visual stimulation shows positive blood-oxygen-level-dependent (BOLD) responses (PBR) in the primary and associative visual cortices. Single vestibular stimulation shows PBR in the parieto-insular vestibular cortex, inferior parietal lobe, superior temporal gyrus, precentral gyrus and lobules V and VI of the cerebellar hemisphere. Simultaneous stimulation shows PBR in the middle and inferior frontal gyri and in the precentral gyrus. Vestibular- and somatosensory-related areas show negative BOLD responses (NBR) during simultaneous stimulation. NBR areas were also observed in the calcarine gyrus, lingual gyrus, cuneus and precuneus during simultaneous and single visual stimulations. For static visual and galvanic vestibular simultaneous stimulation, the reciprocal inhibitory visual-vestibular interaction pattern is observed in our results. The experimental results revealed interactions in frontal areas during concurrent visual-vestibular stimuli, which are affected by intermodal association areas in occipital, parietal, and temporal lobes.

  2. Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care

    PubMed Central

    Bertocchi, Ilaria; Oberto, Alessandra; Longo, Angela; Mele, Paolo; Sabetta, Marianna; Bartolomucci, Alessandro; Palanza, Paola; Sprengel, Rolf; Eva, Carola

    2011-01-01

    Neuropeptide Y (NPY) plays an important role in stress, anxiety, obesity, and energy homeostasis via activation of NPY-Y1 receptors (Y1Rs) in the brain. However, global knockout of the Npy1r gene has low or no impact on anxiety and body weight. To uncover the role of limbic Y1Rs, we generated conditional knockout mice in which the inactivation of the Npy1r gene was restricted to excitatory neurons of the forebrain, starting from juvenile stages (Npy1rrfb). Npy1rrfb mice exhibited increased anxiety and reduced body weight, less adipose tissue, and lower serum leptin levels. Npy1rrfb mutants also had a hyperactive hypothalamic–pituitary–adrenocortical axis, as indicated by higher peripheral corticosterone and higher density of NPY immunoreactive fibers and corticotropin releasing hormone immunoreactive cell bodies in the paraventricular hypothalamic nucleus. Importantly, through fostering experiments, we determined that differences in phenotype between Npy1rrfb and Npy1r2lox mice became apparent when both genotypes were raised by FVB/J but not by C57BL/6J dams, suggesting that limbic Y1Rs are key targets of maternal care-induced programming of anxiety and energy homeostasis. PMID:22084082

  3. Brain perfusion SPECT with Brodmann areas analysis in differentiating frontotemporal dementia subtypes.

    PubMed

    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Psimadas, Dimitrios; Kapsalaki, Eftychia; Fezoulidis, Ioannis; Hadjigeorgiou, George; Georgoulias, Panagiotis

    2014-01-01

    Despite the known validity of clinical diagnostic criteria, significant overlap of clinical symptoms between Frontotemporal dementia (FTD) subtypes exists in several cases, resulting in great uncertainty of the diagnostic boundaries. We evaluated the perfusion between FTD subtypes using brain perfusion (99m)Tc-HMPAO SPECT with Brodmann areas (BA) mapping. NeuroGam software was applied on single photon emission computed tomographic (SPECT) studies for the semi-quantitative evaluation of perfusion in BA and the comparison with the software's normal database. We studied 91 consecutive FTD patients: 21 with behavioural variants (bvFTD), 39 with language variants (lvFTD) [12 with progressive non-fluent aphasia (PNFA), 27 with semantic dementia (SD)], and 31 patients with progressive supranuclear palsy (PSP)/corticobasal degeneration (CBD). Stepwise logistic regression analyses showed that the BA 28L and 32R could independently differentiate bvFTD from lvFTD, while the BA 8R and 25R could discriminate bvFTD from SD and PNFA, respectively. Additionally, BA 7R and 32R were found to discriminate bvFTD from CBD/PSP. The only BA that could differentiate SD from PNFA was 6L. BA 6R and 20L were found to independently differentiate CBD/PSP from lvFTD. Moreover, BA 20L and 22R could discriminate CBD/PSP from PNFA, while BA 6R, 20L and 45R were found to independently discriminate CBD/PSP from SD. Brain perfusion SPECT with BA mapping can be a useful additional tool in differentiating FTD variants by improving the definition of brain areas that are specifically implicated, resulting in a more accurate differential diagnosis in atypical or uncertain forms of FTD.

  4. Gender-Associated Differential Expression of Cytokines in Specific Areas of the Brain During Helminth Infection

    PubMed Central

    López-Griego, Lorena; Nava-Castro, Karen Elizabeth; López-Salazar, Valeria; Hernández-Cervantes, Rosalía; Tiempos Guzmán, Nelly; Muñiz-Hernández, Saé; Hernández-Bello, Romel; Besedovsky, Hugo O.; Pavón, Lenin; Becerril Villanueva, Luis Enrique

    2015-01-01

    Intraperitoneal infection with Taenia crassiceps cysticerci in mice alters several behaviors, including sexual, aggressive, and cognitive function. Cytokines and their receptors are produced in the central nervous system (CNS) by specific neural cell lineages under physiological and pathological conditions, regulating such processes as neurotransmission. This study is aimed to determine the expression patterns of cytokines in various areas of the brain in normal and T. crassiceps-infected mice in both genders and correlate them with the pathology of the CNS and parasite counts. IL-4, IFN-γ, and TNF-α levels in the hippocampus and olfactory bulb increased significantly in infected male mice, but IL-6 was downregulated in these regions in female mice. IL-1β expression in the hippocampus was unaffected by infection in either gender. Our novel findings demonstrate a clear gender-associated pattern of cytokine expression in specific areas of the brain in mammals that parasitic infection can alter. Thus, we hypothesize that intraperitoneal infection is sensed by the CNS of the host, wherein cytokines are important messengers in the host–parasite neuroimmunoendocrine network. PMID:25495255

  5. Gender-associated differential expression of cytokines in specific areas of the brain during helminth infection.

    PubMed

    López-Griego, Lorena; Nava-Castro, Karen Elizabeth; López-Salazar, Valeria; Hernández-Cervantes, Rosalía; Tiempos Guzmán, Nelly; Muñiz-Hernández, Saé; Hernández-Bello, Romel; Besedovsky, Hugo O; Pavón, Lenin; Becerril Villanueva, Luis Enrique; Morales-Montor, Jorge

    2015-02-01

    Intraperitoneal infection with Taenia crassiceps cysticerci in mice alters several behaviors, including sexual, aggressive, and cognitive function. Cytokines and their receptors are produced in the central nervous system (CNS) by specific neural cell lineages under physiological and pathological conditions, regulating such processes as neurotransmission. This study is aimed to determine the expression patterns of cytokines in various areas of the brain in normal and T. crassiceps-infected mice in both genders and correlate them with the pathology of the CNS and parasite counts. IL-4, IFN-γ, and TNF-α levels in the hippocampus and olfactory bulb increased significantly in infected male mice, but IL-6 was downregulated in these regions in female mice. IL-1β expression in the hippocampus was unaffected by infection in either gender. Our novel findings demonstrate a clear gender-associated pattern of cytokine expression in specific areas of the brain in mammals that parasitic infection can alter. Thus, we hypothesize that intraperitoneal infection is sensed by the CNS of the host, wherein cytokines are important messengers in the host-parasite neuroimmunoendocrine network.

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

    PubMed

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

    2014-09-01

    Pre-extinction administration of Δ9-tetrahydrocannibinol (THC) facilitates recall of extinction in healthy humans, and evidence from animal studies suggest that this likely occurs 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 h 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.

  7. The changing landscape of functional brain networks for face processing in typical development

    PubMed Central

    Joseph, Jane E.; Swearingen, Joshua E.; Clark, Jonathan D.; Benca, Chelsie E.; Collins, Heather R.; Corbly, Christine R.; Gathers, Ann D.; Bhatt, Ramesh S.

    2012-01-01

    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 (ROFA). 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. PMID:22906788

  8. Defining Functional Areas in Individual Human Brains using Resting Functional Connectivity MRI

    PubMed Central

    Cohen, Alexander L.; Fair, Damien A.; Dosenbach, Nico U.F.; Miezin, Francis M.; Dierker, Donna; Van Essen, David C.; Schlaggar, Bradley L.; Petersen, Steven E.

    2009-01-01

    The cerebral cortex is anatomically organized at many physical scales starting at the level of single neurons and extending up to functional systems. Current functional magnetic resonance imaging (fMRI) studies often focus at the level of areas, networks, and systems. Except in restricted domains, (e.g. topographically-organized sensory regions), it is difficult to determine area boundaries in the human brain using fMRI. The ability to delineate functional areas non-invasively would enhance the quality of many experimental analyses allowing more accurate across-subject comparisons of independently identified functional areas. Correlations in spontaneous BOLD activity, often referred to as resting state functional connectivity (rs-fcMRI), are especially promising as a way to accurately localize differences in patterns of correlated activity across large expanses of cortex. In the current report, we applied a novel set of image analysis tools to explore the utility of rs-fcMRI for defining wide-ranging functional area boundaries. We find that rs-fcMRI patterns show sharp transitions in correlation patterns and that these putative areal boundaries can be reliably detected in individual subjects as well as in group data. Additionally, combining surface-based analysis techniques with image processing algorithms allows automated mapping of putative areal boundaries across large expanses of cortex without the need for prior information about a region’s function or topography. Our approach reliably produces maps of bounded regions appropriate in size and number for putative functional areas. These findings will hopefully stimulate further methodological refinements and validations. PMID:18367410

  9. Selective insulin resistance in homeostatic and cognitive control brain areas in overweight and obese adults.

    PubMed

    Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2015-06-01

    Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  10. The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI.

    PubMed

    Hui, Kathleen K S; Liu, Jing; Marina, Ovidiu; Napadow, Vitaly; Haselgrove, Christian; Kwong, Kenneth K; Kennedy, David N; Makris, Nikos

    2005-09-01

    Clinical and experimental data indicate that most acupuncture clinical results are mediated by the central nervous system, but the specific effects of acupuncture on the human brain remain unclear. Even less is known about its effects on the cerebellum. This fMRI study demonstrated that manual acupuncture at ST 36 (Stomach 36, Zusanli), a main acupoint on the leg, modulated neural activity at multiple levels of the cerebro-cerebellar and limbic systems. The pattern of hemodynamic response depended on the psychophysical response to needle manipulation. Acupuncture stimulation typically elicited a composite of sensations termed deqi that is related to clinical efficacy according to traditional Chinese medicine. The limbic and paralimbic structures of cortical and subcortical regions in the telencephalon, diencephalon, brainstem and cerebellum demonstrated a concerted attenuation of signal intensity when the subjects experienced deqi. When deqi was mixed with sharp pain, the hemodynamic response was mixed, showing a predominance of signal increases instead. Tactile stimulation as control also elicited a predominance of signal increase in a subset of these regions. The study provides preliminary evidence for an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 that correlates with the psychophysical response.

  11. [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.

  12. Brain Neurons as Quantum Computers:

    NASA Astrophysics Data System (ADS)

    Bershadskii, A.; Dremencov, E.; Bershadskii, J.; Yadid, G.

    The question: whether quantum coherent states can sustain decoherence, heating and dissipation over time scales comparable to the dynamical timescales of brain neurons, has been actively discussed in the last years. A positive answer on this question is crucial, in particular, for consideration of brain neurons as quantum computers. This discussion was mainly based on theoretical arguments. In the present paper nonlinear statistical properties of the Ventral Tegmental Area (VTA) of genetically depressive limbic brain are studied in vivo on the Flinders Sensitive Line of rats (FSL). VTA plays a key role in the generation of pleasure and in the development of psychological drug addiction. We found that the FSL VTA (dopaminergic) neuron signals exhibit multifractal properties for interspike frequencies on the scales where healthy VTA dopaminergic neurons exhibit bursting activity. For high moments the observed multifractal (generalized dimensions) spectrum coincides with the generalized dimensions spectrum calculated for a spectral measure of a quantum system (so-called kicked Harper model, actively used as a model of quantum chaos). This observation can be considered as a first experimental (in vivo) indication in the favor of the quantum (at least partially) nature of brain neurons activity.

  13. Functional connections between optic flow areas and navigationally responsive brain regions during goal-directed navigation.

    PubMed

    Sherrill, Katherine R; Chrastil, Elizabeth R; Ross, Robert S; Erdem, Uğur M; Hasselmo, Michael E; Stern, Chantal E

    2015-09-01

    Recent computational models suggest that visual input from optic flow provides information about egocentric (navigator-centered) motion and influences firing patterns in spatially tuned cells during navigation. Computationally, self-motion cues can be extracted from optic flow during navigation. Despite the importance of optic flow to navigation, a functional link between brain regions sensitive to optic flow and brain regions important for navigation has not been established in either humans or animals. Here, we used a beta-series correlation methodology coupled with two fMRI tasks to establish this functional link during goal-directed navigation in humans. Functionally defined optic flow sensitive cortical areas V3A, V6, and hMT+ were used as seed regions. fMRI data was collected during a navigation task in which participants updated position and orientation based on self-motion cues to successfully navigate to an encoded goal location. The results demonstrate that goal-directed navigation requiring updating of position and orientation in the first person perspective involves a cooperative interaction between optic flow sensitive regions V3A, V6, and hMT+ and the hippocampus, retrosplenial cortex, posterior parietal cortex, and medial prefrontal cortex. These functional connections suggest a dynamic interaction between these systems to support goal-directed navigation. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Cooperation in mind: Motor imagery of joint and single actions is represented in different brain areas.

    PubMed

    Wriessnegger, S C; Steyrl, D; Koschutnig, K; Müller-Putz, G R

    2016-11-01

    In this study brain activity during motor imagery (MI) of joint actions, compared to single actions and rest conditions, was investigated using functional magnetic resonance imaging (fMRI). To the best of our knowledge, this is the first neuroimaging study which directly investigated the neural correlates of joint action motor imagery. Twenty-one healthy participants imagined three different motor tasks (dancing, carrying a box, wiping). Each imagery task was performed at two kinds: alone (single action MI) or with a partner (joint action MI). We hypothesized that to imagine a cooperative task would lead to a stronger cortical activation in motor related areas due to a higher vividness and intensification of the imagery. This would be elicited by the integration of the action simulation of the virtual partner to one's own action. Comparing the joint action and the single action condition with the rest condition, we found significant activation in the precentral gyrus and precuneus respectively. Furthermore the joint action MI showed higher activation patterns in the premotor cortex (inferior and middle frontal gyrus) compared to the single action MI. The imagery of a more vivid and engaging task, like our joint action imagery, could improve rehabilitation processes since a more distributed brain activity is found. Furthermore, the joint action imagery compared to single action imagery might be an appropriate BCI task due to its clear spatial distinction of activation. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. An acute method for multielectrode recording from the interior of sulci and other deep brain areas.

    PubMed

    Purushothaman, Gopathy; Scott, Benjamin B; Bradley, David C

    2006-05-15

    Most current techniques for multielectrode recording involve chronically implanting planar or staggered arrays of electrodes. Such chronic implants are suited for studying a stable population of neurons over long periods of time but exploratory studies of the physiological properties of cortical subdivisions require the ability to sample multiple neural populations. This makes it necessary to penetrate frequently with small multielectrode assemblies. Some commercial systems allow daily penetrations with multiple electrodes, but they tend to be bulky, complex and expensive, and some make no provision for piercing the barrier of fibrous tissue that often covers the brain surface. We describe an apparatus for inserting bundles of 3-16 electrodes on a daily basis, thus allowing different neural populations to be sampled. The system is designed to allow penetration through a thick dura mater into deep brain structures. We discuss a simple method for performing multielectrode recording from cortical areas buried inside sulci using acute implantations of a bundle of electrodes. Our results show that it is possible to obtain stable recordings for at least 4h and that repeated implantations yield an average of two neurons per electrode with every electrode in the bundle picking up at least one single neuron in 70% of the implantations.

  16. Using geographical information systems mapping to identify areas presenting high risk for traumatic brain injury

    PubMed Central

    2011-01-01

    Background The aim of this study is to show how geographical information systems (GIS) can be used to track and compare hospitalization rates for traumatic brain injury (TBI) over time and across a large geographical area using population based data. Results & Discussion Data on TBI hospitalizations, and geographic and demographic variables, came from the Ontario Trauma Registry Minimum Data Set for the fiscal years 1993-1994 and 2001-2002. Various visualization techniques, exploratory data analysis and spatial analysis were employed to map and analyze these data. Both the raw and standardized rates by age/gender of the geographical unit were studied. Data analyses revealed persistent high rates of hospitalization for TBI resulting from any injury mechanism between two time periods in specific geographic locations. Conclusions This study shows how geographic information systems can be successfully used to investigate hospitalizaton rates for traumatic brain injury using a range of tools and techniques; findings can be used for local planning of both injury prevention and post discharge services, including rehabilitation. PMID:22054220

  17. Limbic hyperactivity associated to verbal memory deficit in schizophrenia.

    PubMed

    Suazo, Vanessa; Díez, Álvaro; Tamayo, Pilar; Montes, Carlos; Molina, Vicente

    2013-06-01

    In schizophrenia there seems to be an inefficient activation of prefrontal and hippocampal regions. Patients tend to show worse cognitive performance in functions subserved by those regions as compared to healthy controls in spite of higher regional activation. However, the association between activation abnormalities and cognitive deficits remains without being understood. In the present study, we compared cerebral perfusion using single-photon emission tomography (SPECT) in patients and controls to study the association between activation patterns and cognitive performance in this disease. The SPECT studies were simultaneously obtained with an electrophysiological recording during a P300 paradigm to elicit P3a and P3b components. We included 23 stable patients with paranoid schizophrenia and 29 healthy controls that underwent clinical and cognitive assessments. Patients with schizophrenia showed an increased perfusion in the right hippocampus with respect to healthy controls, they also displayed a statistically significant inverse association between perfusion in the left hippocampus and verbal memory performance. Healthy controls showed an inverse association between perfusion in the left dorsolateral prefrontal (DLPFC) region and working memory performance. P3b but not P3a amplitude was significantly lower in patients. The limbic overactivation in the patients may contribute to their cognitive deficits in verbal memory. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Different aspects of performance feedback engage different brain areas: Disentangling valence and expectancy in feedback processing

    PubMed Central

    Ferdinand, Nicola K.; Opitz, Bertram

    2014-01-01

    Evaluating the positive and negative outcomes of our behaviour is important for action selection and learning. Such reinforcement learning has been shown to engage a specific neural circuitry including the mesencephalic dopamine system and its target areas, the striatum and medial frontal cortex, especially the anterior cingulate cortex (ACC). An intensively pursued debate regards the prevailing influence of feedback expectancy and feedback valence on the engagement of these two brain regions in reinforcement learning and their respective roles are far from being understood. To this end, we used a time estimation task with three different types of feedback that allows disentangling the effect of feedback valence and expectancy using functional magnetic resonance imaging (fMRI). Our results show greater ACC activation after unexpected positive and unexpected negative feedback than after expected feedback and by this sensitivity to unexpected events in general irrespective of their valence. PMID:25100234

  19. Organochlorine Pesticides in Gonad, Brain, and Blood of Mice in Two Agricultural Areas of Sinaloa.

    PubMed

    Perez-Gonzalez, Ernestina; Osuna-Martinez, Ulises-Giovanni; Herrera-Moreno, Maria-Nancy; Rodriguez-Meza, Guadalupe-Durga; Gonzalez-Ocampo, Hector-A; Bucio-Pacheco, Marcos

    2017-04-01

    The adverse effect of pesticides on non-target wildlife and human health is a primary concern in the world, but in Mexico, we do not know which wildlife species are at the greatest risk. The aim of this study was to determine organochlorine pesticides in mice of two agricultural fields in Sinaloa, Culiacan and Guasave. Procedures of extraction, analysis, and quantification were followed according to the modified EPA 8081b method. In three mouse tissues (gonad, brain, and blood), γBHC and decachlorobiphenyl with a frequency higher than 50% and endosulfan sulfate with 43% were observed. The wildlife fauna living in agricultural areas are at great risk due to: (1) diversity of the chemicals used for pest control, like mice, and (2) variety of organochlorine pesticides in direct or indirect contact with non-target organisms, affecting the health of animals and humans (toxic effects and accumulation).

  20. 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.

  1. Orbitofrontal and limbic signatures of empathic concern and intentional harm in the behavioral variant frontotemporal dementia.

    PubMed

    Baez, Sandra; Morales, Juan P; Slachevsky, Andrea; Torralva, Teresa; Matus, Cristian; Manes, Facundo; Ibanez, Agustin

    2016-02-01

    Perceiving and evaluating intentional harms in an interpersonal context engages both cognitive and emotional domains. This process involves inference of intentions, moral judgment, and, crucially, empathy towards others' suffering. This latter skill is notably impaired in behavioral variant frontotemporal dementia (bvFTD). However, the relationship between regional brain atrophy in bvFTD and deficits in the above-mentioned abilities is not well understood. The present study investigated how gray matter (GM) atrophy in bvFTD patients correlates with the perception and evaluation of harmful actions (attribution of intentionality, evaluation of harmful behavior, empathic concern, and moral judgment). First, we compared the behavioral performance of 26 bvFTD patients and 23 healthy controls on an experimental task (ET) indexing intentionality, empathy, and moral cognition during evaluation of harmful actions. Second, we compared GM volume in patients and controls using voxel-based morphometry (VBM). Third, we examined brain regions where atrophy might be associated with specific impairments in the patient group. Finally, we explored whether the patients' deficits in intentionality comprehension and empathic concern could be partially explained by regional GM atrophy or impairments in other relevant factors, such as executive functions (EFs). In bvFTD patients, atrophy of limbic structures (amygdala and anterior paracingulate cortex--APC) was related to impairments in intentionality comprehension, while atrophy of the orbitofrontal cortex (OFC) was associated with empathic concern deficits. Intentionality comprehension impairments were predicted by EFs and orbitofrontal atrophy predicted deficits in empathic concern. Thus, although the perception and evaluation of harmful actions are variously compromised in bvFTD, deficits in empathic concern may be central to this syndrome as they are associated with one of the earliest atrophied region. More generally, our results

  2. Reduced Serotonin Receptor Subtypes in a Limbic and a Neocortical Region in Autism

    PubMed Central

    Oblak, Adrian; Gibbs, Terrell T.; Blatt, Gene J.

    2013-01-01

    Autism is a behaviorally defined, neurological disorder with symptom onset before the age of three. 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 (5HT) is one of the earliest expressed neurotransmitters, and plays an important role in synaptogenesis, neurite outgrowth, and neuronal migration. Abnormalities in 5HT 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 5HT in autism, there is emerging evidence that 5HT systems in the CNS, including various 5HT receptor subtypes and transporters, are affected in autism. The present study demonstrated significant reductions in 5HT1A receptor binding density in superficial and deep layers of the PCC and FG, and in the density of 5HT2A receptors in superficial layers of the PCC and FG. 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. These studies provide 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. PMID:23894004

  3. Anomalous prefrontal-limbic activation and connectivity in youth at high-risk for bipolar disorder.

    PubMed

    Chang, Kiki; Garrett, Amy; Kelley, Ryan; Howe, Meghan; Sanders, Erica Marie; Acquaye, Tenah; Bararpour, Layla; Li, Sherrie; Singh, Manpreet; Jo, Booil; Hallmayer, Joachim; Reiss, Allan

    2017-11-01

    Abnormal prefrontal-limbic brain activation in response to facial expressions has been reported in pediatric bipolar disorder (BD). However, it is less clear whether these abnormalities exist prior to onset of mania, thus representing a biomarker predicting development of BD. We examined brain activation in 50 youth at high risk for BD (HR-BD), compared with 29 age- and gender-matched healthy control (HC) subjects. HR-BD was defined as having a parent with BD, as well as current mood or attentiondeficit/ hyperactivity disorder (ADHD) symptoms, or a history of at least one depressive episode. FMRI data were collected during an implicit emotion perception task using facial expression stimuli. Activation to fearful faces versus calm faces was compared between HR-BD and HC groups, including analyses of functional connectivity, and comparison of allele subgroups of the serotonin transporter (5-HTTLPR) gene. While viewing fearful versus calm faces, HR-BD youth had significantly greater activation than HC youth in the right amygdala, ventrolateral prefrontal cortex (VLPFC), superior frontal cortex, cerebellum, and lingual gyrus. HR-BD youth, relative to HC youth, had greater functional connectivity between the right amygdala and the VLPFC as well as visual cortical regions Within the HR-BD group, youth with the s-allele had a trend for greater activation in the right amygdala and subgenual cingulate cortex CONCLUSIONS: Similar to youth with BD, youth at high risk for BD have greater activation than healthy controls in the amygdala and ventrolateral prefrontal cortex in response to fearful faces, as well greater functional connectivity between these regions. HR-BD youth with the s-allele of the 5-HTTLPR gene may be at greatest risk for developing BD. Copyright © 2017. Published by Elsevier B.V.

  4. GABA Immunoreactivity in Auditory and Song Control Brain Areas of Zebra Finches

    PubMed Central

    Pinaud, Raphael; Mello, Claudio V.

    2009-01-01

    Inhibitory transmission is critical to sensory and motor processing and is believed to play a role in experience-dependent plasticity. The main inhibitory neurotransmitter in vertebrates, GABA, has been implicated in both sensory and motor aspects of vocalization in songbirds. To understand the role of GABAergic mechanisms in vocal communication, GABAergic elements must be characterized fully. Hence, we investigated GABA immunohistochemistry in the zebra finch brain, emphasizing auditory areas and song control nuclei. Several nuclei of the ascending auditory pathway showed a moderate to high density of GABAergic neurons including the cochlear nuclei, nucleus laminaris, superior olivary nucleus, mesencephalic nucleus lateralis pars dorsalis, and nucleus ovoidalis. Telencephalic auditory areas, including field L subfields L1, L2a and L3, as well as the caudomedial nidopallium (NCM) and mesopallium (CMM), contained GABAergic cells at particularly high densities. Considerable GABA labeling was also seen in the shelf area of caudodorsal nidopallium, and the cup area in the arcopallium, as well as in area X, the lateral magnocellular nucleus of the anterior nidopallium, the robust nucleus of the arcopallium and nidopallial nucleus HVC. GABAergic cells were typically small, most likely local inhibitory interneurons, although large GABA-positive cells that were sparsely distributed were also identified. GABA-positive neurites and puncta were identified in most nuclei of the ascending auditory pathway and in song control nuclei. Our data are in accordance with a prominent role of GABAergic mechanisms in regulating the neural circuits involved in song perceptual processing, motor production, and vocal learning in songbirds. PMID:17466487

  5. Neural Processing of Calories in Brain Reward Areas Can be Modulated by Reward Sensitivity

    PubMed Central

    van Rijn, Inge; Griffioen-Roose, Sanne; de Graaf, Cees; Smeets, Paul A. M.

    2016-01-01

    A food's reward value is dependent on its caloric content. Furthermore, a food's acute reward value also depends on hunger state. The drive to obtain rewards (reward sensitivity), however, differs between individuals. Here, we assessed the association between brain responses to calories in the mouth and trait reward sensitivity in different hunger states. Firstly, we assessed this in data from a functional neuroimaging study (van Rijn et al., 2015), in which participants (n = 30) tasted simple solutions of a non-caloric sweetener with or without a non-sweet carbohydrate (maltodextrin) during hunger and satiety. Secondly, we expanded these analyses to regular drinks by assessing the same relationship in data from a study in which soft drinks sweetened with either sucrose or a non-caloric sweetener were administered during hunger (n = 18) (Griffioen-Roose et al., 2013). First, taste activation by the non-caloric solution/soft drink was subtracted from that by the caloric solution/soft drink to eliminate sweetness effects and retain activation induced by calories. Subsequently, this difference in taste activation was correlated with reward sensitivity as measured with the BAS drive subscale of the Behavioral Activation System (BAS) questionnaire. When participants were hungry and tasted calories from the simple solution, brain activation in the right ventral striatum (caudate), right amygdala and anterior cingulate cortex (bilaterally) correlated negatively with BAS drive scores. In contrast, when participants were satiated, taste responses correlated positively with BAS drive scores in the left caudate. These results were not replicated for soft drinks. Thus, neural responses to oral calories from maltodextrin were modulated by reward sensitivity in reward-related brain areas. This was not the case for sucrose. This may be due to the direct detection of maltodextrin, but not sucrose in the oral cavity. Also, in a familiar beverage, detection of calories per se may be

  6. Neural Processing of Calories in Brain Reward Areas Can be Modulated by Reward Sensitivity.

    PubMed

    van Rijn, Inge; Griffioen-Roose, Sanne; de Graaf, Cees; Smeets, Paul A M

    2015-01-01

    A food's reward value is dependent on its caloric content. Furthermore, a food's acute reward value also depends on hunger state. The drive to obtain rewards (reward sensitivity), however, differs between individuals. Here, we assessed the association between brain responses to calories in the mouth and trait reward sensitivity in different hunger states. Firstly, we assessed this in data from a functional neuroimaging study (van Rijn et al., 2015), in which participants (n = 30) tasted simple solutions of a non-caloric sweetener with or without a non-sweet carbohydrate (maltodextrin) during hunger and satiety. Secondly, we expanded these analyses to regular drinks by assessing the same relationship in data from a study in which soft drinks sweetened with either sucrose or a non-caloric sweetener were administered during hunger (n = 18) (Griffioen-Roose et al., 2013). First, taste activation by the non-caloric solution/soft drink was subtracted from that by the caloric solution/soft drink to eliminate sweetness effects and retain activation induced by calories. Subsequently, this difference in taste activation was correlated with reward sensitivity as measured with the BAS drive subscale of the Behavioral Activation System (BAS) questionnaire. When participants were hungry and tasted calories from the simple solution, brain activation in the right ventral striatum (caudate), right amygdala and anterior cingulate cortex (bilaterally) correlated negatively with BAS drive scores. In contrast, when participants were satiated, taste responses correlated positively with BAS drive scores in the left caudate. These results were not replicated for soft drinks. Thus, neural responses to oral calories from maltodextrin were modulated by reward sensitivity in reward-related brain areas. This was not the case for sucrose. This may be due to the direct detection of maltodextrin, but not sucrose in the oral cavity. Also, in a familiar beverage, detection of calories per se may be

  7. Expression of Npas4 mRNA in Telencephalic Areas of Adult and Postnatal Mouse Brain

    PubMed Central

    Damborsky, Joanne C.; Slaton, G. Simona; Winzer-Serhan, Ursula H.

    2015-01-01

    The transcription factor neuronal PAS domain-containing protein 4 (Npas4) is an inducible immediate early gene which regulates the formation of inhibitory synapses, and could have a significant regulatory role during cortical circuit formation. However, little is known about basal Npas4 mRNA expression during postnatal development. Here, postnatal and adult mouse brain sections were processed for isotopic in situ hybridization using an Npas4 specific cRNA antisense probe. In adults, Npas4 mRNA was found in the telencephalon with very restricted or no expression in diencephalon or mesencephalon. In most telencephalic areas, including the anterior olfactory nucleus (AON), piriform cortex, neocortex, hippocampus, dorsal caudate putamen (CPu), septum and basolateral amygdala nucleus (BLA), basal Npas4 expression was detected in scattered cells which exhibited strong hybridization signal. In embryonic and neonatal brain sections, Npas4 mRNA expression signals were very low. Starting at postnatal day 5 (P5), transcripts for Npas4 were detected in the AON, CPu and piriform cortex. At P8, additional Npas4 hybridization was found in CA1 and CA3 pyramidal layer, and in primary motor cortex. By P13, robust mRNA expression was located in layers IV and VI of all sensory cortices, frontal cortex and cingulate cortex. After onset of expression, postnatal spatial mRNA distribution was similar to that in adults, with the exception of the CPu, where Npas4 transcripts became gradually restricted to the most dorsal part. In conclusion, the spatial distribution of Npas4 mRNA is mostly restricted to telencephalic areas, and the temporal expression increases with developmental age during postnatal development, which seem to correlate with the onset of activity-driven excitatory transmission. PMID:26633966

  8. Surgical outcome of encapsulated brain abscess in superficial non-eloquent area: A systematic review.

    PubMed

    Zhai, Yixuan; Wei, Xinting; Chen, Ruokun; Guo, Ziqiang; Raj Singh, Ranjan; Zhang, Yazhuo

    2016-01-01

    To investigate surgical (aspiration and resection) outcome of encapsulated brain abscess in superficial non-eloquent area. We searched Pubmed, Embase and Cochrane Library from the foundation of the database till December 2013. Two researchers screened literatures independently, assessed the quality of the included studies and extracted the data. Revman 5.2.8 was used to do meta-analysis. A total of five studies were included, all retrospective cohort studies. Eighty-four cases were in the abscess aspiration group and 124 cases were in the abscess resection group. Meta-analysis showed that the abscess resection group had lower rate of postoperative residual abscess, lower re-operation rate, higher rate of improvement in neurological status within 1 month after surgery, their OR (95% Confidence Interval (CI)) were 0.12 (0.04, 0.34), 0.07 (0.02, 0.20), 7.9 (3.20, 19.51) respectively; the abscess resection group had shorter duration of post-operative antibiotics and average length of hospital stay; Standard Mean Difference (SMD) (95% CI) were -0.84 (-1.27, -0.41), -1.01 (-1.54, -0.49), respectively. There was no statistically significant difference in the rate of improvement in neurological status at 3 months post-operative and the mortality. Current evidences suggest that for encapsulated brain abscess in superficial non-eloquent area, abscess resection compared to abscess aspiration had lower post-operative residual abscess rate; lower re-operation rate; higher rate of improvement in neurological status within 1 month after surgery, shorter duration of post-operative antibiotics and average length of hospital stay. There was no statistically significant difference in the rate of improvement in neurological status at 3 months post-operative and the mortality.

  9. A learning and memory area in the octopus brain manifests a vertebrate-like long-term potentiation.

    PubMed

    Hochner, Binyamin; Brown, Euan R; Langella, Marina; Shomrat, Tal; Fiorito, Graziano

    2003-11-01

    Cellular mechanisms underlying learning and memory were investigated in the octopus using a brain slice preparation of the vertical lobe, an area of the octopus brain involved in learning and memory. Field potential recordings revealed long-term potentiation (LTP) of glutamatergic synaptic field potentials similar to that in vertebrates. These findings suggest that convergent evolution has led to the selection of similar activity-dependent synaptic processes that mediate complex forms of learning and memory in vertebrates and invertebrates.

  10. 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.

  11. Treatment of limbic encephalitis with anti-glioma-inactivated 1 (LGI1) antibodies.

    PubMed

    Krastinova, E; Vigneron, M; Le Bras, P; Gasnault, J; Goujard, C

    2012-11-01

    We report a 72-year-old patient who developed acute limbic encephalitis initially considered of uncertain aetiology. Detailed information on clinical presentation, MRI appearance, antibody levels, cognitive impairment assessment, treatment and evolution of the patient is reported here. Since the early 2000s, many antibodies implied in central nervous system autoimmune disorders have been identified. Anti-glioma-inactivated 1 (LGI1) antibodies have been recently identified as associated with limbic encephalitis, as was the case in our patient.

  12. 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

  13. Age-related differences and relationships between elements in human amygdala and other limbic system or basal ganglia.

    PubMed

    Tohno, Yoshiyuki; Tohno, Setsuko; Azuma, Cho; Ongkana, Nutcharin; Mahakkanukrauh, Pasuk; Minami, Takeshi; Suwannahoy, Patipath; Viwatpinyo, Kittikun; Ke, Lining

    2013-05-01

    To elucidate the compositional changes of the amygdala with aging, the authors investigated age-related differences of elements in human amygdalae. In addition, the relationships between the amygdala and other brain regions were investigated from a viewpoint of elements. After ordinary dissections at Nara Medical University were finished, the amygdalae were removed from the cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years. In addition, the hippocampus, dentate gyrus, mammillary body of the limbic system and the caudate nucleus, putamen, and globus pallidus of the basal ganglia were also removed from the identical cerebra. After the brain samples were incinerated with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that both the Ca and Mg contents increased significantly in the amygdalae with aging, but the other five element contents (P, S, Zn, Fe, and Na) did not change significantly in the amygdalae with aging. Regarding the relationships among elements, very significant or significant direct correlations were found among the Ca, P, and Mg contents in the amygdalae. To explore the relationships between the amygdala and either other limbic system or basal ganglia, the correlations between seven elements of the amygdala and hippocampus, dentate gyrus, or mammillary body, and between those of the amygdala and caudate nucleus, putamen, or globus pallidus which derived from the identical cerebra, were analyzed with Pearson's correlation. It was found that regarding the four elements of Ca, P, Mg, and Fe, a close relationship existed between the amygdala and hippocampus, globus pallidus, or mammillary body.

  14. A voxel-based lesion study on facial emotion recognition after penetrating brain injury

    PubMed Central

    Dal Monte, Olga; Solomon, Jeffrey M.; Schintu, Selene; Knutson, Kristine M.; Strenziok, Maren; Pardini, Matteo; Leopold, Anne; Raymont, Vanessa; Grafman, Jordan

    2013-01-01

    The ability to read emotions in the face of another person is an important social skill that can be impaired in subjects with traumatic brain injury (TBI). To determine the brain regions that modulate facial emotion recognition, we conducted a whole-brain analysis using a well-validated facial emotion recognition task and voxel-based lesion symptom mapping (VLSM) in a large sample of patients with focal penetrating TBIs (pTBIs). Our results revealed that individuals with pTBI performed significantly worse than normal controls in recognizing unpleasant emotions. VLSM mapping results showed that impairment in facial emotion recognition was due to damage in a bilateral fronto-temporo-limbic network, including medial prefrontal cortex (PFC), anterior cingulate cortex, left insula and temporal areas. Beside those common areas, damage to the bilateral and anterior regions of PFC led to impairment in recognizing unpleasant emotions, whereas bilateral posterior PFC and left temporal areas led to impairment in recognizing pleasant emotions. Our findings add empirical evidence that the ability to read pleasant and unpleasant emotions in other people's faces is a complex process involving not only a common network that includes bilateral fronto-temporo-limbic lobes, but also other regions depending on emotional valence. PMID:22496440

  15. Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder.

    PubMed

    Voon, Valerie; Brezing, Christina; Gallea, Cecile; Hallett, Mark

    2011-11-01

    Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2-button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top-down regulation.

  16. Gender differences in the effects of prenatal stress on brain development and behaviour.

    PubMed

    Weinstock, Marta

    2007-10-01

    An increased incidence of anxiety, depression and attention deficits in children has been linked to psychological stress during pregnancy. Subjection of a pregnant rat to stress at a time when the foetal limbic and hypothalamic pituitary adrenal (HPA) axes develop results in anxiogenic and depressive behaviour and learning and attention deficits in the offspring, which depend on its gender, intensity and timing of the maternal stress and behaviour being tested. Maternal stress increases corticosterone levels in the foetal brain, decreases foetal testosterone and brain aromatase activity in males, and alters brain catecholamine activity to that in females. Learning deficits, reductions in hippocampal neurogenesis, LTP and dendritic spine density in the prefrontal cortex are more readily seen in prenatally-stressed males, while anxiety, depression and increased response of the HPA axis to stress are more prevalent in females. Genders may differ in the sensitivity of developing brain areas to stress hormones.

  17. Molecular Mapping of Movement-Associated Areas in the Avian Brain: A Motor Theory for Vocal Learning Origin

    PubMed Central

    Feenders, Gesa; Liedvogel, Miriam; Rivas, Miriam; Zapka, Manuela; Horita, Haruhito; Hara, Erina; Wada, Kazuhiro; Mouritsen, Henrik; Jarvis, Erich D.

    2008-01-01

    Vocal learning is a critical behavioral substrate for spoken human language. It is a rare trait found in three distantly related groups of birds-songbirds, hummingbirds, and parrots. These avian groups have remarkably similar systems of cerebral vocal nuclei for the control of learned vocalizations that are not found in their more closely related vocal non-learning relatives. These findings led to the hypothesis that brain pathways for vocal learning in different groups evolved independently from a common ancestor but under pre-existing constraints. Here, we suggest one constraint, a pre-existing system for movement control. Using behavioral molecular mapping, we discovered that in songbirds, parrots, and hummingbirds, all cerebral vocal learning nuclei are adjacent to discrete brain areas active during limb and body movements. Similar to the relationships between vocal nuclei activation and singing, activation in the adjacent areas correlated with the amount of movement performed and was independent of auditory and visual input. These same movement-associated brain areas were also present in female songbirds that do not learn vocalizations and have atrophied cerebral vocal nuclei, and in ring doves that are vocal non-learners and do not have cerebral vocal nuclei. A compilation of previous neural tracing experiments in songbirds suggests that the movement-associated areas are connected in a network that is in parallel with the adjacent vocal learning system. This study is the first global mapping that we are aware for movement-associated areas of the avian cerebrum and it indicates that brain systems that control vocal learning in distantly related birds are directly adjacent to brain systems involved in movement control. Based upon these findings, we propose a motor theory for the origin of vocal learning, this being that the brain areas specialized for vocal learning in vocal learners evolved as a specialization of a pre-existing motor pathway that controls

  18. A comparison of neurodegeneration linked with neuroinflammation in different brain areas of rats after intracerebroventricular colchicine injection.

    PubMed

    Sil, Susmita; Ghosh, Rupsa; Sanyal, Moumita; Guha, Debjani; Ghosh, Tusharkanti

    2016-01-01

    Colchicine induces neurodegeneration, but the extent of neurodegeneration in different areas of the brain in relation to neuroinflammation remains unclear. Such information may be useful to allow for the development of a model to compare colchicine-induced neurodegeneration with other neurodegenerative diseases such as Alzheimer's Disease (AD). The present study was designed to investigate the extent of neurodegeneration along with neuroinflammation in different areas of the brain, e.g. frontal cortex, parietal cortex, occipital cortex, corpus striatum, amygdala and hippocampus, in rats along with memory impairment 21 days after a single intracerebroventricular (icv) injection of colchicine. Memory parameters were measured before and after icv colchicine injection in all test groups of rats (control, sham-operated, colchicine-injected [ICIR] rats). On Day 21 post-injection, rats from all groups were anesthesized and tissues from the various brain areas were collected for assessment of biomarkers of neuroinflammation (i.e. levels of ROS, nitrite and proinflammatory cytokines TNFα and IL-1β) and neurodegeneration (assessed histologically). The single injection of colchicine resulted in impaired memory and neurodegeneration (significant presence of plaques, Nissl granule chromatolysis) in various brain areas (frontal cortex, amygdala, parietal cortex, corpus striatum), with maximum severity in the hippocampus. While IL-1β, TNFα, ROS and nitrite levels were altered in different brain areas in the ICIR rats, these parameters had their greatest change in the hippocampus. This study showed that icv injection of colchicine caused strong neurodegeneration and neuroinflammation in the hippocampus of rats and the increases in neurodegeneration were corroborated with those of neuroinflammation at the site. The present study also showed that the extent of neurodegeneration and neuroinflammation in different brain areas of the colchicine-injected rats were AD-like and

  19. Molecular mapping of movement-associated areas in the avian brain: a motor theory for vocal learning origin.

    PubMed

    Feenders, Gesa; Liedvogel, Miriam; Rivas, Miriam; Zapka, Manuela; Horita, Haruhito; Hara, Erina; Wada, Kazuhiro; Mouritsen, Henrik; Jarvis, Erich D

    2008-03-12

    Vocal learning is a critical behavioral substrate for spoken human language. It is a rare trait found in three distantly related groups of birds-songbirds, hummingbirds, and parrots. These avian groups have remarkably similar systems of cerebral vocal nuclei for the control of learned vocalizations that are not found in their more closely related vocal non-learning relatives. These findings led to the hypothesis that brain pathways for vocal learning in different groups evolved independently from a common ancestor but under pre-existing constraints. Here, we suggest one constraint, a pre-existing system for movement control. Using behavioral molecular mapping, we discovered that in songbirds, parrots, and hummingbirds, all cerebral vocal learning nuclei are adjacent to discrete brain areas active during limb and body movements. Similar to the relationships between vocal nuclei activation and singing, activation in the adjacent areas correlated with the amount of movement performed and was independent of auditory and visual input. These same movement-associated brain areas were also present in female songbirds that do not learn vocalizations and have atrophied cerebral vocal nuclei, and in ring doves that are vocal non-learners and do not have cerebral vocal nuclei. A compilation of previous neural tracing experiments in songbirds suggests that the movement-associated areas are connected in a network that is in parallel with the adjacent vocal learning system. This study is the first global mapping that we are aware for movement-associated areas of the avian cerebrum and it indicates that brain systems that control vocal learning in distantly related birds are directly adjacent to brain systems involved in movement control. Based upon these findings, we propose a motor theory for the origin of vocal learning, this being that the brain areas specialized for vocal learning in vocal learners evolved as a specialization of a pre-existing motor pathway that controls

  20. EMX2 protein in the developing mouse brain and olfactory area.

    PubMed

    Mallamaci, A; Iannone, R; Briata, P; Pintonello, L; Mercurio, S; Boncinelli, E; Corte, G

    1998-10-01

    The distribution of EMX2, the protein product of the homeobox gene Emx2, was analyzed in the developing mouse CNS by means of a polyclonal antibody we raised against it. The protein is present in the rostral brain, the olfactory area and a set of scattered cells lying between the nasal pits and the telencephalon. In the cortical neuroepithelium EMX2 is expressed all along the rostro-caudal axis in a graded distribution with a caudal-medial maximum and a rostral-lateral minimum. Anti-EMX2 immunoreactivity is also detectable in Cajal-Retzius cells as well as in apical dendrites of marginal neurons of the cortical plate. We also observe that the EMX2 and EMX1 homeoproteins display complementary expression patterns in olfactory bulbs and amygdaloid complex. Here, they demarcate different neuronal populations, involved in processing olfactory information coming from the vomero-nasal organ and from the main olfactory epithelium, respectively. EMX2 is also detectable in mesencephalic structures, such as the optic tectum and tegmentum. The graded distribution of EMX2 along antero-posterior and medial-lateral axes of the primitive cortex prefigures a role of this protein in the subdivision of the cortex in cytoarchitectonic regions and possibly functional areas, whereas its presence in Cajal-Retzius cells suggests a role in the process of cortical lamination.

  1. Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia)

    PubMed Central

    De Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n=21), to a matched group of typically-developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs pediatric template, groups and between-groups analysis, and laterality indexes assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus, superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke’s area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this specific subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas. PMID:21719430

  2. Abnormal functional lateralization and activity of language brain areas in typical specific language impairment (developmental dysphasia).

    PubMed

    de Guibert, Clément; Maumet, Camille; Jannin, Pierre; Ferré, Jean-Christophe; Tréguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-10-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting structural language (n = 21), to a matched group of typically developing children using a panel of four language tasks neither requiring reading nor metalinguistic skills, including two auditory lexico-semantic tasks (category fluency and responsive naming) and two visual phonological tasks based on picture naming. Data processing involved normalizing the data with respect to a matched pairs paediatric template, groups and between-groups analysis, and laterality indices assessment within regions of interest using single and combined task analysis. Children with specific language impairment exhibited a significant lack of left lateralization in all core language regions (inferior frontal gyrus-opercularis, inferior frontal gyrus-triangularis, supramarginal gyrus and superior temporal gyrus), across single or combined task analysis, but no difference of lateralization for the rest of the brain. Between-group comparisons revealed a left hypoactivation of Wernicke's area at the posterior superior temporal/supramarginal junction during the responsive naming task, and a right hyperactivation encompassing the anterior insula with adjacent inferior frontal gyrus and the head of the caudate nucleus during the first phonological task. This study thus provides evidence that this subtype of specific language impairment is associated with atypical lateralization and functioning of core language areas.

  3. Immunofluorescence localization of the receptor Mas in cardiovascular-related areas of the rat brain.

    PubMed

    Becker, Lenice K; Etelvino, Gisele M; Walther, Thomas; Santos, Robson A S; Campagnole-Santos, Maria J

    2007-09-01

    The G protein-coupled receptor Mas was recently described as an angiotensin-(1-7) [ANG-(1-7)] receptor. In the present study we evaluated the anatomical localization of Mas using immunofluorescence in the central nervous system of adult male Wistar rats. An abundant labeling was found in the hippocampus, amigdala, anterodorsal thalamic nucleus, cortex, and hypoglossal nucleus. More importantly, a dense ANG-(1-7) receptor Mas immunoreactivity was observed in cardiovascular-related areas of the medulla and forebrain, shown in several previous studies as sites for the action of ANG-(1-7) in the brain. A strong staining was found in the nucleus of the solitary tract, caudal and rostral ventrolateral medulla, inferior olive, parvo and magnocellular portions of the paraventricular hypothalamic nucleus, supraoptic nucleus, and lateral preoptic area. Furthermore, Mas staining was predominantly present in neurons. At the medullary sites, a specific and high-intensity binding for rhodamine-ANG-(1-7) was also shown. The specific ANG-(1-7) binding was completely displaced by the anti-Mas antibody or by the ANG-(1-7) antagonist, A-779. The data presented provide the first anatomical basis for the physiological role of ANG-(1-7)/Mas axis in the modulation of different cardiovascular functions and give new insights for clarifying the role of ANG-(1-7) in the central nervous system.

  4. Early auditory processing in area V5/MT+ of the congenitally blind brain.

    PubMed

    Watkins, Kate E; Shakespeare, Timothy J; O'Donoghue, M Clare; Alexander, Iona; Ragge, Nicola; Cowey, Alan; Bridge, Holly

    2013-11-13

    Previous imaging studies of congenital blindness have studied individuals with heterogeneous causes of blindness, which may influence the nature and extent of cross-modal plasticity. Here, we scanned a homogeneous group of blind people with bilateral congenital anophthalmia, a condition in which both eyes fail to develop, and, as a result, the visual pathway is not stimulated by either light or retinal waves. This model of congenital blindness presents an opportunity to investigate the effects of very early visual deafferentation on the functional organization of the brain. In anophthalmic animals, the occipital cortex receives direct subcortical auditory input. We hypothesized that this pattern of subcortical reorganization ought to result in a topographic mapping of auditory frequency information in the occipital cortex of anophthalmic people. Using functional MRI, we examined auditory-evoked activity to pure tones of high, medium, and low frequencies. Activity in the superior temporal cortex was significantly reduced in anophthalmic compared with sighted participants. In the occipital cortex, a region corresponding to the cytoarchitectural area V5/MT+ was activated in the anophthalmic participants but not in sighted controls. Whereas previous studies in the blind indicate that this cortical area is activated to auditory motion, our data show it is also active for trains of pure tone stimuli and in some anophthalmic participants shows a topographic mapping (tonotopy). Therefore, this region appears to be performing early sensory processing, possibly served by direct subcortical input from the pulvinar to V5/MT+.

  5. Hypo- and hyperthyroidism affect NEI concentration in discrete brain areas of adult male rats.

    PubMed

    Ayala, Carolina; Valdez, Susana Ruth; Morero, María Luján Navarra; Soaje, Marta; Carreño, Norma Beatriz; Sanchez, Mónica Silvina; Bittencourt, Jakson Cioni; Jahn, Graciela Alma; Celis, María Ester

    2011-06-01

    To date, there has been only one in vitro study of the relationship between neuropeptide EI (NEI) and the hypothalamic-pituitary-thyroid (HPT) axis. To investigate the possible relationship between NEI and the HPT axis, we developed a rat model of hypothyroidism and hyperthyroidism that allows us to determine whether NEI content is altered in selected brain areas after treatment, as well as whether such alterations are related to the time of day. Hypothyroidism and hyperthyroidism, induced in male rats, with 6-propyl-1-thiouracil and l-thyroxine, respectively, were confirmed by determination of triiodothyronine, total thyroxine, and thyrotropin levels. All groups were studied at the morning and the afternoon. In rats with hypothyroidism, NEI concentration, evaluated on postinduction days 7 and 24, was unchanged or slightly elevated on day 7 but was decreased on day 24. In rats with hyperthyroidism, NEI content, which was evaluated after 4 days of l-thyroxine administration, was slightly elevated, principally in the preoptic area in the morning and in the median eminence-arcuate nucleus and pineal gland in the afternoon, the morning and afternoon NEI contents being similar in the controls. These results provide the bases to pursue the study of the interaction between NEI and the HPT axis. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Defining face perception areas in the human brain: a large-scale factorial fMRI face localizer analysis.

    PubMed

    Rossion, Bruno; Hanseeuw, Bernard; Dricot, Laurence

    2012-07-01

    A number of human brain areas showing a larger response to faces than to objects from different categories, or to scrambled faces, have been identified in neuroimaging studies. Depending on the statistical criteria used, the set of areas can be overextended or minimized, both at the local (size of areas) and global (number of areas) levels. Here we analyzed a whole-brain factorial functional localizer obtained in a large sample of right-handed participants (40). Faces (F), objects (O; cars) and their phase-scrambled counterparts (SF, SO) were presented in a block design during a one-back task that was well matched for difficulty across conditions. A conjunction contrast at the group level {(F-SF) and (F-O)} identified six clusters: in the pulvinar, inferior occipital gyrus (so-called OFA), middle fusiform gyrus (so-called FFA), posterior superior temporal sulcus, amygdala, and anterior infero-temporal cortex, which were all strongly right lateralized. While the FFA showed the largest difference between faces and cars, it also showed the least face-selective response, responding more to cars than scrambled cars. Moreover, the FFA's larger response to scrambled faces than scrambled cars suggests that its face-sensitivity is partly due to low-level visual cues. In contrast, the pattern of activation in the OFA points to a higher degree of face-selectivity. A BOLD latency mapping analysis suggests that face-sensitivity emerges first in the right FFA, as compared to all other areas. Individual brain analyses support these observations, but also highlight the large amount of interindividual variability in terms of number, height, extent and localization of the areas responding preferentially to faces in the human ventral occipito-temporal cortex. This observation emphasizes the need to rely on different statistical thresholds across the whole brain and across individuals to define these areas, but also raises some concerns regarding any objective labeling of these areas

  7. ERP time course and brain areas of spontaneous and intentional goal inferences.

    PubMed

    Van der Cruyssen, Laurens; Van Duynslaeger, Marijke; Cortoos, Aisha; Van Overwalle, Frank

    2009-01-01

    This study measured event-related potentials during spontaneous and intentional goal inferences. Participants read sentences describing the behavior of a target person from which a strong goal or intention could be inferred. The last word of each sentence determined the consistency with the goal induced during preceding sentences. In comparison with behaviors that were consistent with the implied goal, a stronger P200 waveform was obtained when the behaviors were irrelevant with that goal or did not contain goal-directed behavior at all, and this P200 showed considerable parallels between spontaneous and intentional inferences. This indicates that goals were inferred rapidly and automatically while reading the behaviors, irrespective of the participants' spontaneous or intentional instructions. In line with this, source localization (LORETA) of the event-related potentials shows predominantly activation in the temporoparietal junction (TPJ) during and immediately after goal detection (225-300 ms). Before and after this time interval, however, activation is stronger at the TPJ during spontaneous processing, and stronger at the medial prefrontal cortex (mPFC) during intentional processing. Memory measures taken after the presentation of the stimulus materials support the occurrence of goal inferences and show significant correlations with the neural components, indicating that these components are valid neural indices of spontaneous and intentional goal inferences. The results are highly similar to previous ERP research on trait inferences that revealed a similar division of brain activation for spontaneous (TPJ) and intentional (mPFC) processes, but appearing later at about 600 ms, pointing to similar brain areas recruited for social inferences, but at different timings for different inference types.

  8. Clinical Evaluation of Brain Perfusion SPECT with Brodmann Areas Mapping in Early Diagnosis of Alzheimer's Disease.

    PubMed

    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Psimadas, Dimitrios; Fezoulidis, Ioannis; Kapsalaki, Eftychia; Hadjigeorgiou, George; Georgoulias, Panagiotis

    2015-01-01

    Early diagnosis of Alzheimer's disease (AD) based on clinical criteria alone may be problematic, while current and future treatments should be administered earlier in order to be more effective. Thus, various disease biomarkers could be used for early detection of AD. We evaluated brain perfusion with 99mTc-HMPAO single photon emission computed tomography (SPECT) and Brodmann areas (BAs) mapping in mild AD using an automated software (NeuroGam) for the semi-quantitative evaluation of perfusion in BAs and the comparison with the software's normal database. We studied 34 consecutive patients with mild AD: 9 men, 25 women, mean age 70.9 ± 8.1 years, mean Mini-Mental State Examination 22.6 ± 2.5. BAs 25L, 25R, 38L, 38R, 28L, 28R, 36L, and 36R had the lower mean perfusion values, while BAs 31L, 31R, 19R, 18L, 18R, 17L, and 17R had the higher mean values. Compared with healthy subjects of the same age, perfusion values in BAs 25L, 25R, 28R, 28L, 36L, and 36R had the greatest deviations from the healthy sample, while the lowest deviations were found in BAs 32L, 32R, 19R, 24L, 17L, 17R, 18L, and 18R. A percentage of ≥94% of patients had perfusion values more than -2SDs below the mean of healthy subjects in BAs 38R, 38L, 36L, 36R, 23L, 23R, 22L, 44L, 28L, 28R, 25L, and 25R. The corresponding proportion was less than 38% for BAs 11L, 19R, 32L, 32R, 18L, 18R, 24L, and 17R. In conclusion, brain SPECT studies with automated perfusion mapping could be useful as an ancillary tool in daily practice, revealing perfusion impairments in early AD.

  9. Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain

    PubMed Central

    Liang, Winnie S.; Dunckley, Travis; Beach, Thomas G.; Grover, Andrew; Mastroeni, Diego; Walker, Douglas G.; Caselli, Richard J.; Kukull, Walter A.; McKeel, Daniel; Morris, John C.; Hulette, Christine; Schmechel, Donald; Alexander, Gene E.; Reiman, Eric M.; Rogers, Joseph; Stephan, Dietrich A.

    2008-01-01

    In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer’s disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders. PMID:17077275

  10. Sex Differences in Functional Brain Activation during Noxious Visceral Stimulation in Rats

    PubMed Central

    Bradesi, Sylvie; Labus, Jennifer S.; Maarek, Jean-Michel I.; Lee, Kevin; Winchester, Wendy J.; Mayer, Emeran A.; Holschneider, Daniel P.

    2009-01-01

    Studies in healthy human subjects and patients with irritable bowel syndrome suggest sex differences in cerebral nociceptive processing. Here we examine sex differences in functional brain activation in the rat during colorectal distention (CRD), a preclinical model of acute visceral pain. [14C]-iodoantipyrine was injected intravenously in awake, nonrestrained female rats during 60-mmHg or 0-mmHg CRD while electromyographic abdominal activity (EMG) and pain behavior were recorded. Regional cerebral blood flow related tissue radioactivity was analyzed by statistical parametric mapping from autoradiographic images of 3-dimensionally reconstructed brains. Sex differences were addressed by comparing current data with our previously published data collected from male rats. While sex differences in EMG and pain scores were modest, significant differences were noted in functional brain activation. Females showed widespread changes in limbic (amygdala, hypothalamus) and paralimbic structures (ventral striatum, nucleus accumbens, raphe), while males demonstrated broad cortical changes. Sex differences were apparent in the homeostatic afferent network (parabrachial nucleus, thalamus, insular and dorsal anterior cingulate cortices), in an emotional-arousal network (amygdala, locus coeruleus complex), and in cortical areas modulating these networks (prefrontal cortex). Greater activation of the ventromedial prefrontal cortex and broader limbic/paralimbic changes in females suggest greater engagement of affective mechanisms during visceral pain. Greater cortical activation in males is consistent with the concept of greater cortical inhibitory effects on limbic structures in males, which may relate to differences in attentional and cognitive attribution to visceral stimuli. These findings show remarkable similarities to reported sex differences in brain responses to visceral stimuli in humans. PMID:19560270

  11. Brain Response to a Humanoid Robot in Areas Implicated in the Perception of Human Emotional Gestures

    PubMed Central

    Chaminade, Thierry; Zecca, Massimiliano; Blakemore, Sarah-Jayne; Takanishi, Atsuo; Frith, Chris D.; Micera, Silvestro; Dario, Paolo; Rizzolatti, Giacomo; Gallese, Vittorio; Umiltà, Maria Alessandra

    2010-01-01

    Background The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents. Methodology Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust) and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted. Principal Findings Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca's area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance. Conclusions Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions. Significance Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions. PMID:20657777

  12. Differences in prefrontal, limbic, and white matter lesion volumes according to cognitive status in elderly patients with first-onset subsyndromal depression.

    PubMed

    Lee, Jun-Young; Park, Soowon; Mackin, Scott; Ewers, Michael; Chui, Helena; Jagust, William; Insel, Philip S; Weiner, Michael W

    2014-01-01

    The purpose of this preliminary study was to test the hypothesis that subsyndromal depression is associated with the volume of medial prefrontal regional gray matter and that of white matter lesions (WMLs) in the brains of cognitively normal older people. We also explored the relationships between subsyndromal depression and medial prefrontal regional gray matter volume, limbic regional gray matter volume, and lobar WMLs in the brains of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). We performed a cross-sectional study comparing patients with subsyndromal depression and nondepressed controls with normal cognition (n = 59), MCI (n = 27), and AD (n = 27), adjusting for sex, age, years of education, and results of the Mini-Mental State Examination. Frontal WML volume was greater, and right medial orbitofrontal cortical volume was smaller in cognitively normal participants with subsyndromal depression than in those without subsyndromal depression. No volume differences were observed in medial prefrontal, limbic, or WML volumes according to the presence of subsyndromal depression in cognitively impaired patients. The absence of these changes in patients with MCI and AD suggests that brain changes associated with AD pathology may override the changes associated with subsyndromal depression.

  13. Effect of environmental temperature on the turnover of noradrenaline in hypothalamus and other areas of rat brain

    PubMed Central

    Simmonds, M. A.

    1969-01-01

    1. The hypothesis that noradrenaline (NA) may be a transmitter in the temperature regulating centre in the hypothalamus is based on the changes in rectal temperature induced by injection of large doses of NA into the brain. As an alternative approach, the effect of environmental temperature on the rate of turnover of endogenous NA in the hypothalamus has been studied. 2. Small amounts of tritium labelled noradrenaline [3H]NA were injected into the c.s.f. of rats in order to label radioactively the endogenous NA in the brain. The rats were then exposed to environmental temperatures of 9, 17, 24 and 32° C. The rates of disappearance of [3H]NA from discrete areas of brain were taken as indices of the rates of turnover of endogenous NA in those areas. 3. The rate of disappearance of [3H]NA from the hypothalamus was three times as fast at 9 and 32° C as at 17 or 24° C. There were no such significant differences from the pre-optic area or `rest of brain' (whole brain minus hypothalamus, pre-optic area, cerebellum and medulla). 4. The endogenous concentrations of NA were not altered by the experimental procedures in any of the areas of brain studied. 5. The rats maintained normal rectal temperatures at environmental temperatures of 9, 17 and 24° C but became 2·8° C hyperthermic at 32° C. 6. It is concluded that mild conditions of both heat and cold resulted in an increased turnover of NA in specific nerve terminals in the hypothalamus. Since the rats were thermoregulating normally, the nerve terminals involved are regarded as forming a part of the central temperature regulating centre. PMID:5821872

  14. Brain alterations potentially associated with aggression and terrorism.

    PubMed

    Bogerts, Bernhard; Schöne, Maria; Breitschuh, Stephanie

    2017-08-14

    A large proportion of the persons who join terrorist groups as well as lone-acting terrorists have a history of violent behavior or mental disorder that predated their becoming terrorists. This suggests that brain alterations found to occur in violent perpetrators may also be present in a significant percentage of terrorists. After a short delineation of phylogenetically old neuronal networks that are important for the generation of aggressive behavior in inconspicuous brains, this review summarizes structural and functional brain-imaging studies in violent offenders published over the last 10 years. Depending on the subtype of violence (impulsive or instrumental), deviations in structure or function were mainly found in the prefrontal, orbitofrontal, and insular cortex, as well as in temporolimbic structures (e.g., the amygdala, hippocampus, and parahippocampus). These brain areas are essentially responsible for the control of the archaic neuronal generators of aggression located in the hypothalamus and limbic system. This regional distribution of brain alterations also shows a remarkable overlap with those brain regions that are crucial for such prosocial traits as empathy and compassion. Feelings of superiority, dominance, and satisfaction gained by performing violent and terroristic attacks suggest that a hedonistic component via an activation of brain reward systems plays an additional role. In our current debate about the causes of terrorism, aspects of brain dysfunction should receive more attention.

  15. Response to deep brain stimulation in the lateral hypothalamic area in a rat model of obesity: in vivo assessment of brain glucose metabolism.

    PubMed

    Soto-Montenegro, María Luisa; Pascau, Javier; Desco, Manuel

    2014-12-01

    To investigate changes in glucose brain metabolism after deep brain stimulation (DBS) in the lateral hypothalamic area (LHA) in a rat model of obesity. Ten obese male Zucker rats were divided into two groups: LHA-control and LHA-DBS. Concentric bipolar platinum-iridium electrodes were implanted bilaterally. After 7 days, DBS was applied for 15 days. Weight and food and water intake were monitored. 2-Deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) PET-CT imaging studies were performed the day after the end of DBS. Differences in glucose uptake between the groups were assessed with statistical parametric mapping. A difference in weight gain of 3.19 percentage points was found between groups. Average food consumption during the first 15 days was lower in DBS-treated animals than in non-stimulated animals. DBS increased metabolism in the mammillary body, subiculum-hippocampal area, and amygdala, while a decrease in metabolism was recorded in the thalamus, caudate, temporal cortex, and cerebellum. DBS produced significant changes in brain regions associated with the control of food intake and the brain reward system. DBS seems to normalize the impaired hippocampal functioning that has been described in obese rats. The smaller weight gain in the DBS group suggests that this technique could be considered an option for the treatment of obesity.

  16. Development and Structural Variety of the Chondroitin Sulfate Proteoglycans-Contained Extracellular Matrix in the Mouse Brain.

    PubMed

    Horii-Hayashi, Noriko; Sasagawa, Takayo; Matsunaga, Wataru; Nishi, Mayumi

    2015-01-01

    Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix (ECM) in the brain. In adult mammals, CSPGs form the specialized ECM structure perineuronal nets (PNNs) that surround somata and dendrites of certain types of neurons. PNNs restrict synaptic plasticity and regulate the closure of critical periods. Although previous studies have examined the starting period of PNN formation, focusing on primary sensory cortices, there are no systematic studies at the whole brain level. Here, we examined the starting period of PNN formation in male mice ranging in age from postnatal day 3 to week 11, mainly focusing on several cortical areas, limbic structures, hypothalamus, and brain stem, using lectin histochemistry with Wisteria floribunda agglutinin (WFA). Results showed that early PNN formation was observed in several reticular formations of the brain stem related to the cranial nerves and primary somatosensory cortices. In the limbic system, PNN formation in the hippocampus started earlier than that of the amygdala. Furthermore, in the medial amygdaloid nucleus and some hypothalamic regions, WFA labeling did not show typical PNN-like forms. The present study suggests spatiotemporal differences at the beginning of PNN formation and a structural variety of CSPG-contained ECM in the brain.

  17. Projections from the laterodorsal nucleus of the thalamus to the limbic and visual cortices in the rat.

    PubMed

    van Groen, T; Wyss, J M

    1992-10-15

    The laterodorsal nucleus (LD) of the thalamus is an important source of thalamic afferents to the limbic cortex, but the topography and lamination of these projections has not been investigated in detail. Using the anterograde transport of Phaseolus vulgaris leucoagglutinin and Fluoro-Ruby, the present study demonstrates that in the rat, LD projects to infraradiata, precentral agranular, retrosplenial, visual (area 18b), subicular, and entorhinal cortices. Each subregion of LD has a distinct pattern of terminals within these cortical areas. The rostral part and the dorsalmost part of LD project densely to retrosplenial granular a (Rga) cortex, presubiculum and parasubiculum. Slightly more caudal parts of dorsal LD project primarily to the postsubiculum. More ventral parts of LD project primarily to retrosplenial dysgranular (Rdg) and retrosplenial granular b (Rgb) cortices. The projection of LD to area 18b originates from cells in the caudalmost part of LD. In each cortical region, LD terminals display distinct laminar patterns. In area 18b and the adjacent Rdg cortex, the LD terminal field is in layers I, III, and IV, but in both the Rgb and Rga cortices the terminal field is located predominantly in layer I. In the postsubiculum the LD terminals are distributed to layers I and III/IV and extend into superficial layer V; in the presubiculum and the parasubiculum the LD terminals are only in the deep layers (i.e., layers IV-VI). A small number of LD axons terminate in the deep layers (i.e., layers IV-VI) of the medial entorhinal cortex. These results indicate that each area of LD has a distinct projection to limbic and adjacent neocortex.

  18. Prolonged Repeated Acupuncture Stimulation Induces Habituation Effects in Pain-Related Brain Areas: An fMRI Study

    PubMed Central

    Li, Chuanfu; Yang, Jun; Park, Kyungmo; Wu, Hongli; Hu, Sheng; Zhang, Wei; Bu, Junjie; Xu, Chunsheng; Qiu, Bensheng; Zhang, Xiaochu

    2014-01-01

    Most previous studies of brain responses to acupuncture were designed to investigate the acupuncture instant effect while the cumulative effect that should be more important in clinical practice has seldom been discussed. In this study, the neural basis of the acupuncture cumulative effect was analyzed. For this experiment, forty healthy volunteers were recruited, in which more than 40 minutes of repeated acupuncture stimulation was implemented at acupoint Zhusanli (ST36). Three runs of acupuncture fMRI datasets were acquired, with each run consisting of two blocks of acupuncture stimulation. Besides general linear model (GLM) analysis, the cumulative effects of acupuncture were analyzed with analysis of covariance (ANCOVA) to find the association between the brain response and the cumulative duration of acupuncture stimulation in each stimulation block. The experimental results showed that the brain response in the initial stage was the strongest although the brain response to acupuncture was time-variant. In particular, the brain areas that were activated in the first block and the brain areas that demonstrated cumulative effects in the course of repeated acupuncture stimulation overlapped in the pain-related areas, including the bilateral middle cingulate cortex, the bilateral paracentral lobule, the SII, and the right thalamus. Furthermore, the cumulative effects demonstrated bimodal characteristics, i.e. the brain response was positive at the beginning, and became negative at the end. It was suggested that the cumulative effect of repeated acupuncture stimulation was consistent with the characteristic of habituation effects. This finding may explain the neurophysiologic mechanism underlying acupuncture analgesia. PMID:24821143

  19. Asymmetry of White Matter Pathways in Developing Human Brains.

    PubMed

    Song, Jae W; Mitchell, Paul D; Kolasinski, James; Ellen Grant, P; Galaburda, Albert M; Takahashi, Emi

    2015-09-01

    Little is known about the emergence of structural asymmetry of white matter tracts during early brain development. We examined whether and when asymmetry in diffusion parameters of limbic and association white matter pathways emerged in humans in 23 brains ranging from 15 gestational weeks (GW) up to 3 years of age (11 ex vivo and 12 in vivo cases) using high-angular resolution diffusion imaging tractography. Age-related development of laterality was not observed in a limbic connectional pathway (cingulum bundle or fornix). Among the studied cortico-cortical association pathways (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus, and arcuate fasciculus), only the ILF showed development of age-related laterality emerging as early as the second trimester. Comparisons of ages older and younger than 40 GW revealed a leftward asymmetry in the cingulum bundle volume and a rightward asymmetry in apparent diffusion coefficient and leftward asymmetry in fractional anisotropy in the ILF in ages older than 40 GW. These results suggest that morphometric asymmetry in cortical areas precedes the emergence of white matter pathway asymmetry. Future correlative studies will investigate whether such asymmetry is anatomically/genetically driven or associated with functional stimulation.

  20. Injured Brain Regions Associated with Anxiety in Vietnam Veterans

    PubMed Central

    Knutson, Kristine M.; Rakowsky, Shana T.; Solomon, Jeffrey; Krueger, Frank; Raymont, Vanessa; Tierney, Michael C.; Wassermann, Eric M.; Grafman, Jordan

    2013-01-01

    Anxiety negatively affects quality of life and psychosocial functioning. Previous research has shown that anxiety symptoms in healthy individuals are associated with variations in the volume of brain regions, such as the amygdala, hippocampus, and the bed nucleus of the stria terminalis. Brain lesion data also suggests the hemisphere damaged may affect levels of anxiety. We studied a sample of 182 male Vietnam War veterans with penetrating brain injuries, using a semi-automated voxel-based lesion-symptom mapping (VLSM) approach. VLSM reveals significant associations between a symptom such as anxiety and the location of brain lesions, and does not require a broad, subjective assignment of patients into categories based on lesion location. We found that lesioned brain regions in cortical and limbic areas of the left hemisphere, including middle, inferior and superior temporal lobe, hippocampus, and fusiform regions, along with smaller areas in the inferior occipital lobe, parahippocampus, amygdala, and insula, were associated with increased anxiety symptoms as measured by the Neurobehavioral Rating Scale (NRS). These results were corroborated by similar findings using Neuropsychiatric Inventory (NPI) anxiety scores, which supports these regions’ role in regulating anxiety. In summary, using a semi-automated analysis tool, we detected an effect of focal brain damage on the presentation of anxiety. We also separated the effects of brain injury and war experience by including a control group of combat veterans without brain injury. We compared this control group against veterans with brain lesions in areas associated with anxiety, and against veterans with lesions only in other brain areas. PMID:23328629

  1. Injured brain regions associated with anxiety in Vietnam veterans.

    PubMed

    Knutson, Kristine M; Rakowsky, Shana T; Solomon, Jeffrey; Krueger, Frank; Raymont, Vanessa; Tierney, Michael C; Wassermann, Eric M; Grafman, Jordan

    2013-03-01

    Anxiety negatively affects quality of life and psychosocial functioning. Previous research has shown that anxiety symptoms in healthy individuals are associated with variations in the volume of brain regions, such as the amygdala, hippocampus, and the bed nucleus of the stria terminalis. Brain lesion data also suggests the hemisphere damaged may affect levels of anxiety. We studied a sample of 182 male Vietnam War veterans with penetrating brain injuries, using a semi-automated voxel-based lesion-symptom mapping (VLSM) approach. VLSM reveals significant associations between a symptom such as anxiety and the location of brain lesions, and does not require a broad, subjective assignment of patients into categories based on lesion location. We found that lesioned brain regions in cortical and limbic areas of the left hemisphere, including middle, inferior and superior temporal lobe, hippocampus, and fusiform regions, along with smaller areas in the inferior occipital lobe, parahippocampus, amygdala, and insula, were associated with increased anxiety symptoms as measured by the Neurobehavioral Rating Scale (NRS). These results were corroborated by similar findings using Neuropsychiatric Inventory (NPI) anxiety scores, which supports these regions' role in regulating anxiety. In summary, using a semi-automated analysis tool, we detected an effect of focal brain damage on the presentation of anxiety. We also separated the effects of brain injury and war experience by including a control group of combat veterans without brain injury. We compared this control group against veterans with brain lesions in areas associated with anxiety, and against veterans with lesions only in other brain areas. Published by Elsevier Ltd.

  2. Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats.

    PubMed

    Ellgren, Maria; Spano, Sabrina M; Hurd, Yasmin L

    2007-03-01

    Cannabis use is a hypothesized gateway to subsequent abuse of other drugs such as heroin. We currently assessed whether Delta-9-tetrahydrocannabinol (THC) exposure during adolescence modulates opiate reinforcement and opioid neural systems in adulthood. Long-Evan male rats received THC (1.5 mg/kg intraperitoneally (i.p.)) or vehicle every third day during postnatal days (PNDs) 28-49. Heroin self-administration behavior (fixed ratio-1; 3-h sessions) was studied from young adulthood (PND 57) into full adults (PND 102). THC-pretreated rats showed an upward shift throughout the heroin self-administration acquisition (30 microg/kg/infusion) phase, whereas control animals maintained the same pattern once stable intake was obtained. Heightened opiate sensitivity in THC animals was also evidenced by higher heroin consumption during the maintenance phase (30 and 60 microg/kg/infusion) and greater responding for moderate-low heroin doses (dose-response curve: 7.5, 15, 30, 60, and 100 microg/kg/injection). Specific disturbance of the endogenous opioid system was also apparent in the brain of adults with adolescent THC exposure. Striatal preproenkephalin mRNA expression was exclusively increased in the nucleus accumbens (NAc) shell; the relative elevation of preproenkephalin mRNA in the THC rats was maintained even after heroin self-administration. Moreover, mu opioid receptor (muOR) GTP-coupling was potentiated in mesolimbic and nigrostriatal brainstem regions in THC-pretreated animals. muOR function in the NAc shell was specifically correlated to heroin intake. The current findings support the gateway hypothesis demonstrating that adolescence cannabis exposure has an enduring impact on hedonic processing resulting in enhanced opiate intake, possibly as a consequence of alterations in limbic opioid neuronal populations.

  3. 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

  4. Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training.

    PubMed

    Morena, Maria; Roozendaal, Benno; Trezza, Viviana; Ratano, Patrizia; Peloso, Andrea; Hauer, Daniela; Atsak, Piray; Trabace, Luigia; Cuomo, Vincenzo; McGaugh, James L; Schelling, Gustav; Campolongo, Patrizia

    2014-12-23

    Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The experiments first examined whether the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are released by aversive training. Inhibitory avoidance training with higher footshock intensity produced increased levels of AEA in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) shortly after training in comparison with levels assessed in rats trained with lower footshock intensity or unshocked controls exposed only to the training apparatus. In contrast, 2-AG levels were not significantly elevated. The additional finding that posttraining infusions of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which selectively increases AEA levels at active synapses, administered into the basolateral complex of the amygdala (BLA), hippocampus, or mPFC enhanced memory strongly suggests that the endogenously released AEA modulates memory consolidation. Moreover, in support of the view that this emotional training-associated increase in endocannabinoid neurotransmission, and its effects on memory enhancement, depends on the integrity of functional interactions between these different brain regions, we found that disruption of BLA activity blocked the training-induced increases in AEA levels as well as the memory enhancement produced by URB597 administered into the hippocampus or mPFC. Thus, the findings provide evidence that emotionally arousing training increases AEA levels within prefrontal-limbic circuits and strongly suggest that this cannabinoid activation regulates emotional arousal effects on memory consolidation.

  5. Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training

    PubMed Central

    Morena, Maria; Roozendaal, Benno; Trezza, Viviana; Ratano, Patrizia; Peloso, Andrea; Hauer, Daniela; Atsak, Piray; Trabace, Luigia; Cuomo, Vincenzo; McGaugh, James L.; Schelling, Gustav; Campolongo, Patrizia

    2014-01-01

    Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The experiments first examined whether the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are released by aversive training. Inhibitory avoidance training with higher footshock intensity produced increased levels of AEA in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) shortly after training in comparison with levels assessed in rats trained with lower footshock intensity or unshocked controls exposed only to the training apparatus. In contrast, 2-AG levels were not significantly elevated. The additional finding that posttraining infusions of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which selectively increases AEA levels at active synapses, administered into the basolateral complex of the amygdala (BLA), hippocampus, or mPFC enhanced memory strongly suggests that the endogenously released AEA modulates memory consolidation. Moreover, in support of the view that this emotional training-associated increase in endocannabinoid neurotransmission, and its effects on memory enhancement, depends on the integrity of functional interactions between these different brain regions, we found that disruption of BLA activity blocked the training-induced increases in AEA levels as well as the memory enhancement produced by URB597 administered into the hippocampus or mPFC. Thus, the findings provide evidence that emotionally arousing training increases AEA levels within prefrontal-limbic circuits and strongly suggest that this cannabinoid activation regulates emotional arousal effects on memory consolidation. PMID:25489086

  6. FMRI study relevant to the Mozart effect: brain areas involved in spatial-temporal reasoning.

    PubMed

    Bodner, M; Muftuler, L T; Nalcioglu, O; Shaw, G L

    2001-10-01

    Behavioral studies, motivated by columnar cortical model predictions, have given evidence for music causally enhancing spatial-temporal reasoning. A wide range of behavioral experiments showed that listening to a Mozart Sonata (K.448) gave subsequent enhancements. An EEG coherence study gave evidence for a carryover from that Mozart Sonata listening condition to the subsequent spatial-temporal task in specific cortical regions. Here we present fMRI studies comparing cortical blood flow activation by the Mozart Sonata vs. other music. In addition to expected temporal cortex activation, we report dramatic statistically significant differences in activation by the Mozart Sonata (in comparison to Beethoven's Fur Elise and 1930s piano music) in dorsolateral pre-frontal cortex, occipital cortex and cerebellum, all expected to be important for spatial-temporal reasoning. It would be of great interest to explicitly test this expectation. We propose an fMRI study comparing (subject by subject) brain areas activated in music listening conditions and in spatial-temporal tasks.

  7. Large-area low-noise seven-channel dc SQUID magnetometer for brain research

    SciTech Connect

    Knuutila, J.; Ahlfors, S.; Ahonen, A.; Haellstroem, J.; Kajola, M.; Lounasmaa, O.V.; Vilkman, V.; Tesche, C.

    1987-11-01

    The design, construction, and performance of a new high-sensitivity dc SQUID magnetometer, covering a circular area of 93-mm diameter, is described. The device, now used routinely in our brain research, comprises seven asymmetric first-order gradiometers, located on a spherical surface of 125-mm radius and with the symmetry axis tilted 30/sup 0/ with respect to the vertical. The pickup coil diameter is 20 mm, and the channels are separated by 36.5 mm from each other in a hexagonal array. The overall field sensitivity of the system, measured inside our magnetically shielded room, is 5 fT/(Hz)/sup 1/2/, mainly limited by the thermal noise in the radiation shields of the Dewar. The optimization of the coil configuration and the measurement system is discussed in detail, and a system to determine automatically the position and orientation of the Dewar with respect to certain fixed points on the subject's head is described. Finally, some examples of measurements carried out with the new device are given.

  8. Brain Arteriovenous Malformations Located in Language Area: Surgical Outcomes and Risk Factors for Postoperative Language Deficits.

    PubMed

    Jiao, Yuming; Lin, Fuxin; Wu, Jun; Li, Hao; Chen, Xin; Li, Zhicen; Ma, Ji; Cao, Yong; Wang, Shuo; Zhao, Jizong

    2017-09-01

    Case selection for surgical treatment of language-area brain arteriovenous malformations (L-BAVMs) remains difficult. This study aimed to determine the surgical outcomes and risk factors for postoperative language deficits (LDs) in patients with L-BAVMs. Patients with L-BAVMs who underwent microsurgical resection between September 2012 and June 2016 were reviewed. All patients had undergone preoperative functional magnetic resonance imaging and diffusion tensor imaging. Both functional and angioarchitectural factors were analyzed regarding the postoperative LD. Functional factors included the eloquence involved, the side of blood-oxygenation level-dependent signal activation and the white-matter fibers (anterior segment, long segment [LS], and posterior segment of arcuate fasciculus, and the inferior fronto-occipital fasciculus) involved. Sixty-nine patients with L-BAVMs were reviewed. Postoperative short- and long-term LD was found in 32 (46.4%) and 14 (20.3%) patients, respectively. Twelve of the 14 patients with Geschwind's territory L-BAVMs (85.7%) had short-term LD, compared with 10 (34.5%) in Wernicke's and 10 (38.5%) in Broca's area. LS involvement (P = 0.001) and larger nidus size (P = 0.017) were independent risk factors for the short-term LD. Meanwhile, nidus size (P = 0.007), preoperative LD (P = 0.008), and LS involvement (P = 0.028) were independent risk factors for long-term LD. L-BAVMs located in Geschwind's territory can cause a high incidence of LD. LS involvement and larger nidus size are risk factors for postoperative short- and long-term LD, and preoperative LD is a risk factor for postoperative, long-term LD. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Modulation of the extinction of two different fear-motivated tasks in three distinct brain areas.

    PubMed

    Fiorenza, Natalia Gindri; Rosa, Jessica; Izquierdo, Ivan; Myskiw, Jociane C

    2012-06-15

    The hippocampus, basolateral amygdala and ventromedial prefrontal cortex participate in the extinction of inhibitory avoidance and contextual fear conditioning. We studied the effect of drugs acting on receptors involved in synaptic modulation on extinction of both tasks. The drugs were given bilaterally right after the first of two sessions of extinction in each task through cannulae implanted into the mentioned areas. The doses used are known to influence memory consolidation of the original tasks. Their effects were evaluated on a second extinction session 24h later, and assumed to result from influences on the consolidation of extinction. The glutamate NMDA receptor stimulant d-serine (50 μg/side) and the histamine methyl-transferase inhibitor SKF9188 (12.5 μg/side) enhanced, and the NMDA antagonist amino-phosphonopentanoate (5 μg/side) and the H2 histamine receptor antagonist ranitidine (17.5 μg/side) inhibited, extinction of both tasks regardless of the region into which they were administered. Thus, glutamate NMDA receptors are involved in the consolidation of extinction of both tasks, and histamine H2 receptors modulate that process in all areas studied. Norepinephrine (1 μg/side), the β-adrenoceptor antagonist timolol (1 μg/side), the D1 dopamine receptor agonist SKF38393 (12.5 μg/side) and the D1 antagonist SCH23390 (1.5 μg/side) also affected extinction of both tasks, but their effects varied with the task and with the site of infusion, suggesting that extinction modulation by β- and D1 receptors is more complex. In conclusion, extinction of two different aversive tasks is modulatable by various systems, which bears upon the behavioral and pharmacological treatment of fear-motivated brain disorders.

  10. 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.

  11. 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.

  12. 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.

  13. 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

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

    PubMed

    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.

  15. 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

  16. Imaging of superoxide generation in the dopaminergic area of the brain in Parkinson's disease, using mito-TEMPO.

    PubMed

    Zhelev, Zhivko; Bakalova, Rumiana; Aoki, Ichio; Lazarova, Dessislava; Saga, Tsuneo

    2013-11-20

    We report a new methodology for direct visualization of superoxide production in the dopaminergic area of the brain in Parkinson's disease, based on the redox cycle of mito-TEMPO, a blood-brain barrier-, cell-, and mitochondria-penetrating nitroxide derivative with superoxide scavenging properties and T1 magnetic resonance imaging (MRI) contrast. The experiments were conducted on healthy and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. In healthy mice, the nitroxide-enhanced MRI signal was weak and short-lived (half-life ∼ 40 s; duration ∼ 80 s). The profile of the histograms indicated a high reducing activity of normal brain tissues against mito-TEMPO. In MPTP-treated mice, the nitroxide-enhanced MRI signal was strong and long-lived (half-life > 20 min; duration > 20 min), especially in the dopaminergic area of the brain. The histograms indicated a high oxidative activity in dopaminergic tissues of MPTP-treated mice. The results show directly, on intact mammals, that superoxide is a major inducer and/or mediator of neurodegenerative damage in Parkinson's disease. The high oxidative status of brain tissue in Parkinson's disease was also confirmed on isolated tissue specimens, using total reducing capacity assay and ROS/RNS assay.

  17. Imaging of Superoxide Generation in the Dopaminergic Area of the Brain in Parkinson’s Disease, Using Mito-TEMPO

    PubMed Central

    2013-01-01

    We report a new methodology for direct visualization of superoxide production in the dopaminergic area of the brain in Parkinson’s disease, based on the redox cycle of mito-TEMPO, a blood-brain barrier-, cell-, and mitochondria-penetrating nitroxide derivative with superoxide scavenging properties and T1 magnetic resonance imaging (MRI) contrast. The experiments were conducted on healthy and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. In healthy mice, the nitroxide-enhanced MRI signal was weak and short-lived (half-life ∼ 40 s; duration ∼ 80 s). The profile of the histograms indicated a high reducing activity of normal brain tissues against mito-TEMPO. In MPTP-treated mice, the nitroxide-enhanced MRI signal was strong and long-lived (half-life > 20 min; duration > 20 min), especially in the dopaminergic area of the brain. The histograms indicated a high oxidative activity in dopaminergic tissues of MPTP-treated mice. The results show directly, on intact mammals, that superoxide is a major inducer and/or mediator of neurodegenerative damage in Parkinson’s disease. The high oxidative status of brain tissue in Parkinson’s disease was also confirmed on isolated tissue specimens, using total reducing capacity assay and ROS/RNS assay. PMID:24024751

  18. Neck muscle cross-sectional area, brain volume and cognition in healthy older men: a cohort study.

    PubMed

    Kilgour, Alixe H M; Ferguson, Karen J; Gray, Calum D; Deary, Ian J; Wardlaw, Joanna M; MacLullich, Alasdair M J; Starr, John M

    2013-02-28

    Two important consequences of the normal ageing process are sarcopenia (the age-related loss of muscle mass and function) and age-related cognitive decline. Existing data support positive relationships between muscle function, cognition and brain structure. However, studies investigating these relationships at older ages are lacking and rarely include a measure of muscle size. Here we test whether neck muscle size is positively associated with cognition and brain structure in older men. We studied 51 healthy older men with mean age 73.8 (sd 1.5) years. Neck muscle cross-sectional area (CSA) was measured from T1-weighted MR-brain scans using a validated technique. We measured multiple cognitive domains including verbal and visuospatial memory, executive functioning and estimated prior cognitive ability. Whole brain, ventricular, hippocampal and cerebellar volumes were measured with MRI. General linear models (ANCOVA) were performed. Larger neck muscle CSA was associated with less whole brain atrophy (t = 2.86, p = 0.01, partial eta squared 17%). Neck muscle CSA was not associated with other neuroimaging variables or current cognitive ability. Smaller neck muscle CSA was unexpectedly associated with higher prior cognition (t = -2.12, p < 0.05, partial eta squared 10%). In healthy older men, preservation of whole brain volume (i.e. less atrophy) is associated with larger muscle size. Longitudinal ageing studies are now required to investigate these relationships further.

  19. Specificities of Awake Craniotomy and Brain Mapping in Children for Resection of Supratentorial Tumors in the Language Area.

    PubMed

    Delion, Matthieu; Terminassian, Aram; Lehousse, Thierry; Aubin, Ghislaine; Malka, Jean; N'Guyen, Sylvie; Mercier, Philippe; Menei, Philippe

    2015-12-01

    In the pediatric population, awake craniotomy began to be used for the resection of brain tumor located close to eloquent areas. Some specificities must be taken into account to adapt this method to children. The aim of this clinical study is to not only confirm the feasibility of awake craniotomy and language brain mapping in the pediatric population but also identify the specificities and necessary adaptations of the procedure. Six children aged 11 to 16 were operated on while awake under local anesthesia with language brain mapping for supratentorial brain lesions (tumor and cavernoma). The preoperative planning comprised functional magnetic resonance imaging (MRI) and neuropsychologic and psychologic assessment. The specific preoperative preparation is clearly explained including hypnosis conditioning and psychiatric evaluation. The success of the procedure was based on the ability to perform the language brain mapping and the tumor removal without putting the patient to sleep. We investigated the pediatric specificities, psychological experience, and neuropsychologic follow-up. The children experienced little anxiety, probably in large part due to the use of hypnosis. We succeeded in doing the cortical-subcortical mapping and removing the tumor without putting the patient to sleep in all cases. The psychological experience was good, and the neuropsychologic follow-up showed a favorable evolution. Preoperative preparation and hypnosis in children seemed important for performing awake craniotomy and contributing language brain mapping with the best possible psychological experience. The pediatrics specificities are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Mania secondary to focal brain lesions: implications for understanding the functional neuroanatomy of bipolar disorder.

    PubMed

    Satzer, David; Bond, David J

    2016-05-01

    Approximately 3.5 million Americans will experience a manic episode during their lifetimes. The most common causes are psychiatric illnesses such as bipolar I disorder and schizoaffective disorder, but mania can also occur secondary to neurological illnesses, brain injury, or neurosurgical procedures. For this narrative review, we searched Medline for articles on the association of mania with stroke, brain tumors, traumatic brain injury, multiple sclerosis, neurodegenerative disorders, epilepsy, and neurosurgical interventions. We discuss the epidemiology, features, and treatment of these cases. We also review the anatomy of the lesions, in light of what is known about the neurobiology of bipolar disorder. The prevalence of mania in patients with brain lesions varies widely by condition, from <2% in stroke to 31% in basal ganglia calcification. Mania occurs most commonly with lesions affecting frontal, temporal, and subcortical limbic brain areas. Right-sided lesions causing hypo-functionality or disconnection (e.g., stroke; neoplasms) and left-sided excitatory lesions (e.g., epileptogenic foci) are frequently observed. Secondary mania should be suspected in patients with neurological deficits, histories atypical for classic bipolar disorder, and first manic episodes after the age of 40 years. Treatment with antimanic medications, along with specific treatment for the underlying neurologic condition, is typically required. Typical lesion locations fit with current models of bipolar disorder, which implicate hyperactivity of left-hemisphere reward-processing brain areas and hypoactivity of bilateral prefrontal emotion-modulating regions. Lesion studies complement these models by suggesting that right-hemisphere limbic-brain hypoactivity, or a left/right imbalance, may be relevant to the pathophysiology of mania. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Stroke Induces Mesenchymal Stem Cell Migration to Infarcted Brain Areas Via CXCR4 and C-Met Signaling.

    PubMed

    Bang, Oh Young; Moon, Gyeong Joon; Kim, Dong Hee; Lee, Ji Hyun; Kim, Sooyoon; Son, Jeong Pyo; Cho, Yeon Hee; Chang, Won Hyuk; Kim, Yun-Hee

    2017-05-25

    Mesenchymal stem cells circulate between organs to repair and maintain tissues. Mesenchymal stem cells cultured with fetal bovine serum have therapeutic effects when intravenously administered after stroke. However, only a small number of mesenchymal stem cells reach the brain. We hypothesized that the serum from stroke patients increases mesenchymal stem cells trophism toward the infarcted brain area. Mesenchymal stem cells were grown in fetal bovine serum, normal serum from normal rats, or stroke serum from ischemic stroke rats. Compared to the fetal bovine serum group, the stroke serum group but not the normal serum group showed significantly greater migration toward the infarcted brain area in the in vitro and in vivo models (p < 0.05). Both C-X-C chemokine receptor type 4 and c-Met expression levels significantly increased in the stroke serum group than the others. The enhanced mesenchymal stem cells migration of the stroke serum group was abolished by inhibition of signaling. Serum levels of chemokines, cytokines, matrix metalloproteinase, and growth factors were higher in stroke serum than in normal serum. Behavioral tests showed a significant improvement in the recovery after stroke in the stroke serum group than the others. Stroke induces mesenchymal stem cells migration to the infarcted brain area via C-X-C chemokine receptor type 4 and c-Met signaling. Culture expansion using the serum from stroke patients could constitute a novel preconditioning method to enhance the therapeutic efficiency of mesenchymal stem cells.

  2. Bilinguals use language-control brain areas more than monolinguals to perform non-linguistic switching tasks.

    PubMed

    Rodríguez-Pujadas, Aina; Sanjuán, Ana; Ventura-Campos, Noelia; Román, Patricia; Martin, Clara; Barceló, Francisco; Costa, Albert; Avila, César

    2013-01-01

    We tested the hypothesis that early bilinguals use language-control brain areas more than monolinguals when performing non-linguistic executive control tasks. We do so by exploring the brain activity of early bilinguals and monolinguals in a task-switching paradigm using an embedded critical trial design. Crucially, the task was designed such that the behavioural performance of the two groups was comparable, allowing then to have a safer comparison between the corresponding brain activity in the two groups. Despite the lack of behavioural differences between both groups, early bilinguals used language-control areas--such as left caudate, and left inferior and middle frontal gyri--more than monolinguals, when performing the switching task. Results offer direct support for the notion that, early bilingualism exerts an effect in the neural circuitry responsible for executive control. This effect partially involves the recruitment of brain areas involved in language control when performing domain-general executive control tasks, highlighting the cross-talk between these two domains.

  3. Fat/carbohydrate ratio but not energy density determines snack food intake and activates brain reward areas.

    PubMed

    Hoch, Tobias; Kreitz, Silke; Gaffling, Simone; Pischetsrieder, Monika; Hess, Andreas

    2015-05-14

    The snack food potato chips induces food intake in ad libitum fed rats, which is associated with modulation of the brain reward system and other circuits. Here, we show that food intake in satiated rats is triggered by an optimal fat/carbohydrate ratio. Like potato chips, an isocaloric fat/carbohydrate mixture influenced whole brain activity pattern of rats, affecting circuits related e.g. to reward/addiction, but the number of modulated areas and the extent of modulation was lower compared to the snack food itself.

  4. Limbic Encephalitis: Potential Impact of Adaptive Autoimmune Inflammation on Neuronal Circuits of the Amygdala.

    PubMed

    Melzer, Nico; Budde, Thomas; Stork, Oliver; Meuth, Sven G

    2015-01-01

    Limbic encephalitis is characterized by adaptive autoimmune inflammation of the gray matter structures of the limbic system. It has recently been identified as a major cause of temporal lobe epilepsy accompanied by progressive declarative - mainly episodic - -memory disturbance as well as a variety of rather poorly defined emotional and behavioral changes. While autoimmune inflammation of the hippocampus is likely to be responsible for declarative memory disturbance, consequences of autoimmune inflammation of the amygdala are largely unknown. The amygdala is central for the generation of adequate homoeostatic behavioral responses to emotionally significant external stimuli following processing in a variety of parallel neuronal circuits. Here, we hypothesize that adaptive cellular and humoral autoimmunity may target and modulate distinct inhibitory or excitatory neuronal networks within the amygdala, and thereby strongly impact processing of emotional stimuli and corresponding behavioral responses. This may explain some of the rather poorly understood neuropsychiatric symptoms in limbic encephalitis.

  5. Hand posture classification using electrocorticography signals in the gamma band over human sensorimotor brain areas.

    PubMed

    Chestek, Cynthia A; Gilja, Vikash; Blabe, Christine H; Foster, Brett L; Shenoy, Krishna V; Parvizi, Josef; Henderson, Jaimie M

    2013-04-01

    Brain-machine interface systems translate recorded neural signals into command signals for assistive technology. In individuals with upper limb amputation or cervical spinal cord injury, the restoration of a useful hand grasp could significantly improve daily function. We sought to determine if electrocorticographic (ECoG) signals contain sufficient information to select among multiple hand postures for a prosthetic hand, orthotic, or functional electrical stimulation system. We recorded ECoG signals from subdural macro- and microelectrodes implanted in motor areas of three participants who were undergoing inpatient monitoring for diagnosis and treatment of intractable epilepsy. Participants performed five distinct isometric hand postures, as well as four distinct finger movements. Several control experiments were attempted in order to remove sensory information from the classification results. Online experiments were performed with two participants. Classification rates were 68%, 84% and 81% for correct identification of 5 isometric hand postures offline. Using 3 potential controls for removing sensory signals, error rates were approximately doubled on average (2.1×). A similar increase in errors (2.6×) was noted when the participant was asked to make simultaneous wrist movements along with the hand postures. In online experiments, fist versus rest was successfully classified on 97% of trials; the classification output drove a prosthetic hand. Online classification performance for a larger number of hand postures remained above chance, but substantially below offline performance. In addition, the long integration windows used would preclude the use of decoded signals for control of a BCI system. These results suggest that ECoG is a plausible source of command signals for prosthetic grasp selection. Overall, avenues remain for improvement through better electrode designs and placement, better participant training, and characterization of non-stationarities such

  6. Hand posture classification using electrocorticography signals in the gamma band over human sensorimotor brain areas

    NASA Astrophysics Data System (ADS)

    Chestek, Cynthia A.; Gilja, Vikash; Blabe, Christine H.; Foster, Brett L.; Shenoy, Krishna V.; Parvizi, Josef; Henderson, Jaimie M.

    2013-04-01

    Objective. Brain-machine interface systems translate recorded neural signals into command signals for assistive technology. In individuals with upper limb amputation or cervical spinal cord injury, the restoration of a useful hand grasp could significantly improve daily function. We sought to determine if electrocorticographic (ECoG) signals contain sufficient information to select among multiple hand postures for a prosthetic hand, orthotic, or functional electrical stimulation system.Approach. We recorded ECoG signals from subdural macro- and microelectrodes implanted in motor areas of three participants who were undergoing inpatient monitoring for diagnosis and treatment of intractable epilepsy. Participants performed five distinct isometric hand postures, as well as four distinct finger movements. Several control experiments were attempted in order to remove sensory information from the classification results. Online experiments were performed with two participants. Main results. Classification rates were 68%, 84% and 81% for correct identification of 5 isometric hand postures offline. Using 3 potential controls for removing sensory signals, error rates were approximately doubled on average (2.1×). A similar increase in errors (2.6×) was noted when the participant was asked to make simultaneous wrist movements along with the hand postures. In online experiments, fist versus rest was successfully classified on 97% of trials; the classification output drove a prosthetic hand. Online classification performance for a larger number of hand postures remained above chance, but substantially below offline performance. In addition, the long integration windows used would preclude the use of decoded signals for control of a BCI system. Significance. These results suggest that ECoG is a plausible source of command signals for prosthetic grasp selection. Overall, avenues remain for improvement through better electrode designs and placement, better participant training

  7. Hand posture classification using electrocorticography signals in the gamma band over human sensorimotor brain areas

    PubMed Central

    Chestek, Cynthia A.; Gilja, Vikash; Blabe, Christine H.; Foster, Brett L.; Shenoy, Krishna V.; Parvizi, Josef; Henderson, Jaimie M.

    2013-01-01

    Objective Brain machine interface systems translate recorded neural signals into command signals for assistive technology. In individuals with upper limb amputation or cervical spinal cord injury, the restoration of a useful hand grasp could significantly improve daily function. We sought to determine if electrocorticographic (ECoG) signals contain sufficient information to select among multiple hand postures for a prosthetic hand, orthotic, or functional electrical stimulation system. Approach We recorded ECoG signals from subdural macro- and microelectrodes implanted in motor areas of three participants who were undergoing inpatient monitoring for diagnosis and treatment of intractable epilepsy. Participants performed 5 distinct isometric hand postures, as well as 4 distinct finger movements. Several control experiments were attempted in order to remove sensory information from the classification results. Online experiments were performed with 2 participants. Main Results Classification rates were 68%, 84%, and 81% for correct identification of 5 isometric hand postures offline. Using 3 potential controls for removing sensory signals, error rates were approximately doubled on average (2.1×). A similar increase in errors (2.6×) was noted when the participant was asked to make simultaneous wrist movements along with the hand postures. In online experiments, fist versus rest was successfully classified on 97% of trials; the classification output drove a prosthetic hand. Online classification performance for a larger number of hand postures remained above chance, but substantially below offline performance. In addition, the long integration windows used would preclude the use of decoded signals for control of a BCI system. Significance These results suggest that ECoG is a plausible source of command signals for prosthetic grasp selection. Overall, avenues remain for improvement through better electrode designs and placement, better participant training, and

  8. Radioimmunoassay of met-enkephalin in microdissected areas of paraformaldehyde-fixed rat brain

    SciTech Connect

    Correa, F.M.A.; Saavedra, J.M.

    1984-02-27

    The effects were studied of various sample preparation procedures on rat brain met-enkephalin content, measured by radioimmunoassay. Whole brain met-enkephalin content of rats killed by decapitation followed by immediate tissue freezing was similar to that of rats killed by microwave irradiation and to those of rats anesthetized with pentobarbital or halothane before killing, whether previously perfused with paraformaldehyde or not. In contrast, a decrease (up to 80%) in met-enkephalin concentrations was observed when brain samples were frozen and thawed to mimic the procedure utilized in the ''punch'' technique for analysis of discrete brain nuclei. This decrease was totally prevented by paraformaldehyde perfusion of the brain prior to sacrifice. Brain perfusion did not alter the amount of immunoassayable met-enkephalin extracted from tissue or its profile after Sephadex chromatography. Paraformaldehyde perfusion results in better morphological tissue preservation and facilitates the ''punch'' dissecting technique. Paraformaldehyde perfusion may be the procedure of choice for the measurement of neuropeptides in specific brain nuclei dissected by the ''punch'' technique.

  9. Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder

    PubMed Central

    Voon, V; Brezing, C; Gallea, C; Hallett, M

    2014-01-01

    Background Conversion disorder is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that conversion disorder with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amgydala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Methods Subjects performed either an internally or externally generated two-button action selection task in a functional MRI study. Results Eleven conversion disorder patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. Conclusion We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system which is both hypoactive and functionally disconnected from prefrontal top-down regulation. PMID:21935985

  10. Characterizing Acupuncture Stimuli Using Brain Imaging with fMRI - A Systematic Review and Meta-Analysis of the Literature

    PubMed Central

    Huang, Wenjing; Pach, Daniel; Napadow, Vitaly; Park, Kyungmo; Long, Xiangyu; Neumann, Jane; Maeda, Yumi; Nierhaus, Till; Liang, Fanrong; Witt, Claudia M.

    2012-01-01

    Background The mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points. Methodology/Principal Findings We systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any language restrictions. We included all studies using fMRI to investigate the effect of acupuncture on the human brain (at least one group that received needle-based acupuncture). 779 papers were identified, 149 met the inclusion criteria for the descriptive analysis, and 34 were eligible for the meta-analyses. From a descriptive perspective, multiple studies reported that acupuncture modulates activity within specific brain areas, including somatosensory cortices, limbic system, basal