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Sample records for limbic brain areas

  1. Redefining the Role of Limbic Areas in Cortical Processing.

    PubMed

    Chanes, Lorena; Barrett, Lisa Feldman

    2016-02-01

    There is increasing evidence that the brain actively constructs action and perception using past experience. In this paper, we propose that the direction of information flow along gradients of laminar differentiation provides important insight on the role of limbic cortices in cortical processing. Cortical limbic areas, with a simple laminar structure (e.g., no or rudimentary layer IV), send 'feedback' projections to lower level better laminated areas. We propose that this 'feedback' functions as predictions that drive processing throughout the cerebral cortex. This hypothesis has the potential to provide a unifying framework for an increasing number of proposals that use predictive coding to explain a myriad of neural processes and disorders, and has important implications for hypotheses about consciousness. PMID:26704857

  2. 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

  3. 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. PMID:26286685

  4. c-Fos immunoreactivity in prefrontal, basal ganglia and limbic areas of the rat brain after central and peripheral administration of ethanol and its metabolite acetaldehyde

    PubMed Central

    Segovia, Kristen N.; Vontell, Regina; López-Cruz, Laura; Salamone, John D.; Correa, Mercè

    2013-01-01

    Considerable evidence indicates that the metabolite of ethanol (EtOH), acetaldehyde, is biologically active. Acetaldehyde can be formed from EtOH peripherally mainly by alcohol dehydrogenase (ADH), and also centrally by catalase. EtOH and acetaldehyde show differences in their behavioral effects depending upon the route of administration. In terms of their effects on motor activity and motivated behaviors, when administered peripherally acetaldehyde tends to be more potent than EtOH but shows very similar potency administered centrally. Since dopamine (DA) rich areas have an important role in regulating both motor activity and motivation, the present studies were undertaken to compare the effects of central (intraventricular, ICV) and peripheral (intraperitoneal, IP) administration of EtOH and acetaldehyde on a cellular marker of brain activity, c-Fos immunoreactivity, in DA innervated areas. Male Sprague-Dawley rats received an IP injection of vehicle, EtOH (0.5 or 2.5 g/kg) or acetaldehyde (0.1 or 0.5 g/kg) or an ICV injection of vehicle, EtOH or acetaldehyde (2.8 or 14.0 μmoles). IP administration of EtOH minimally induced c-Fos in some regions of the prefrontal cortex and basal ganglia, mainly at the low dose (0.5 g/kg), while IP acetaldehyde induced c-Fos in virtually all the structures studied at both doses. Acetaldehyde administered centrally increased c-Fos in all areas studied, a pattern that was very similar to EtOH. Thus, IP administered acetaldehyde was more efficacious than EtOH at inducing c-Fos expression. However, the general pattern of c-Fos induction promoted by ICV EtOH and acetaldehyde was similar. These results are consistent with the pattern observed in behavioral studies in which both substances produced the same magnitude of effect when injected centrally, and produced differences in potency after peripheral administration. PMID:23745109

  5. Blood-brain barrier changes with kainic acid-induced limbic seizures

    SciTech Connect

    Zucker, D.K.; Wooten, G.F.; Lothman, E.W.

    1983-02-01

    Rats were treated with kainic acid (KA) i.v. to produce increasingly severe limbic seizures that were monitored with a behavioral rating scale. At various times after the induction of seizures, the animals; blood-brain barriers (B-BB) were studied with alpha-(/sup 14/C)aminoisobutyric acid ((/sup 14/C)AIBA) autoradiography. Using optical density ratios, a coefficient was devised to assess the functional integrity of the B-BB in discrete anatomic regions and to quantitatively compare these measurements among different groups of experimental animals. In animals that exhibited only mild seizures, the B-BB was not different from controls. Animals with severe limbic seizures, however, showed alterations. For as long as 2 h after delivery of KA, the B-BB appeared normal; from 2 to 24 h, the permeability to (/sup 14/C)AIBA was markedly increased throughout the brain, especially in limbic regions; from 24 h to 7 days the B-BB returned to normal except for a small residual change in limbic structures. These findings were confirmed with Evans blue dye studies of the B-BB. A correlation between focal accentuation of B-BB alterations and neuropathologic changes was found. These experiments indicted that recurrent limbic seizures may lead to a breakdown in the B-BB independent of systemic metabolic derangements. Marked focal metabolic and electrical changes, however, occurred in several limbic structures several hours before the blood-brain barrier was altered.

  6. 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. PMID:25278250

  7. 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

  8. 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

  9. Heritability of Subcortical and Limbic Brain Volume and Shape in Multiplex-Multigenerational Families with Schizophrenia

    PubMed Central

    Roalf, David R.; Vandekar, Simon N.; Almasy, Laura; Ruparel, Kosha; Satterthwaite, Theodore D.; Elliott, Mark A.; Podell, Jamie; Gallagher, Sean; Jackson, Chad T.; Prasad, Konasale; Wood, Joel; Pogue-Geile, Michael F.; Nimgaonkar, Vishwajit L.; Gur, Ruben C.; Gur, Raquel E.

    2014-01-01

    Background Brain abnormalities of subcortical and limbic nuclei are common in schizophrenia and variation in these structures is considered a putative endophenotype for the disorder. Multiplex-Multigenerational families afflicted by schizophrenia provide an opportunity to investigate the impact of shared genetic ancestry, but have not been previously examined to study structural brain abnormalities. Here we estimate the heritability of subcortical and hippocampal brain volumes in such families and the heritability of sub-regions using advanced shape analysis. Methods 439 participants from two sites completed 3-Tesla structural magnetic resonance imaging. They included 190 European-Americans from 32 Multiplex- Multigenerational families with schizophrenia and 249 healthy comparison subjects. Subcortical and hippocampal volume and shape were measured in 14 brain structures. Heritability was estimated for volume and shape. Results Volume and shape were heritable in families. Estimates of heritability in subcortical and limbic volumes ranged from 0.45 in the right hippocampus up to 0.84 in the left putamen. The shape of these structures was heritable (range: 0.40–0.49) and specific sub-regional shape estimates of heritability tended to exceed heritability estimates of volume alone. Conclusions These results demonstrate that volume and shape of subcortical and limbic brain structures are potential endophenotypic markers in schizophrenia. The specificity obtained using shape analysis may improve selection of imaging phenotypes that better reflect the underlying neurobiology. Our findings can aid in the identification of specific genetic targets that affect brain structure and function in schizophrenia. PMID:24976379

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

    PubMed

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

    2016-01-01

    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. PMID:26529483

  11. A novel analytical brain block tool to enable functional annotation of discriminatory transcript biomarkers among discrete regions of the fronto-limbic circuit in primate brain.

    PubMed

    Dalgard, Clifton L; Jacobowitz, David M; Singh, Vijay K; Saleem, Kadharbatcha S; Ursano, Robert J; Starr, Joshua M; Pollard, Harvey B

    2015-03-10

    Fronto-limbic circuits in the primate brain are responsible for executive function, learning and memory, and emotions, including fear. Consequently, changes in gene expression in cortical and subcortical brain regions housing these circuits are associated with many important psychiatric and neurological disorders. While high quality gene expression profiles can be identified in brains from model organisms, primate brains have unique features such as Brodmann Area 25, which is absent in rodents, yet profoundly important in primates, including humans. The potential insights to be gained from studying the human brain are complicated by the fact that the post-mortem interval (PMI) is variable, and most repositories keep solid tissue in the deep frozen state. Consequently, sampling the important medial and internal regions of these brains is difficult. Here we describe a novel method for obtaining discrete regions from the fronto-limbic circuits of a 4 year old and a 5 year old, male, intact, frozen non-human primate (NHP) brain, for which the PMI is exactly known. The method also preserves high quality RNA, from which we use transcriptional profiling and a new algorithm to identify region-exclusive RNA signatures for Area 25 (NFκB and dopamine receptor signaling), the anterior cingulate cortex (LXR/RXR signaling), the amygdala (semaphorin signaling), and the hippocampus (Ca(++) and retinoic acid signaling). The RNA signatures not only reflect function of the different regions, but also include highly expressed RNAs for which function is either poorly understood, or which generate proteins presently lacking annotated functions. We suggest that this new approach will provide a useful strategy for identifying changes in fronto-limbic system biology underlying normal development, aging and disease in the human brain. PMID:25529630

  12. 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

  13. 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

  14. 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.

  15. Increased anxiety in corticotropin-releasing factor type 2 receptor-null mice requires recent acute stress exposure and is associated with dysregulated serotonergic activity in limbic brain areas

    PubMed Central

    2014-01-01

    Background Corticotropin-releasing factor type 2 receptors (CRFR2) are suggested to facilitate successful recovery from stress to maintain mental health. They are abundant in the midbrain raphe nuclei, where they regulate serotonergic neuronal activity and have been demonstrated to mediate behavioural consequences of stress. Here, we describe behavioural and serotonergic responses consistent with maladaptive recovery from stressful challenge in CRFR2-null mice. Results CRFR2-null mice showed similar anxiety levels to control mice before and immediately after acute restraint stress, and also after cessation of chronic stress. However, they showed increased anxiety by 24 hours after restraint, whether or not they had been chronically stressed. Serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents were quantified and the level of 5-HIAA in the caudal dorsal raphe nucleus (DRN) was increased under basal conditions in CRFR2-null mice, indicating increased 5-HT turnover. Twenty-four hours following restraint, 5-HIAA was decreased only in CRFR2-null mice, suggesting that they had not fully recovered from the challenge. In efferent limbic structures, CRFR2-null mice showed lower levels of basal 5-HT in the lateral septum and subiculum, and again showed a differential response to restraint stress from controls. Local cerebral glucose utilization (LCMRglu) revealed decreased neuronal activity in the DRN of CRFR2-null mice under basal conditions. Following 5-HT receptor agonist challenge, LCMRglu responses indicated that 5-HT1A receptor responses in the DRN were attenuated in CRFR2-null mice. However, postsynaptic 5-HT receptor responses in forebrain regions were intact. Conclusions These results suggest that CRFR2 are required for proper functionality of 5-HT1A receptors in the raphe nuclei, and are key to successful recovery from stress. This disrupted serotonergic function in CRFR2-null mice likely contributes to their stress-sensitive phenotype. The 5-HT

  16. 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

    2016-01-01

    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

  17. 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

  18. 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.

  19. Differential changes of metabolic brain activity and interregional functional coupling in prefronto-limbic pathways during different stress conditions: functional imaging in freely behaving rodent pups

    PubMed Central

    Bock, Jörg; Riedel, Anett; Braun, Katharina

    2012-01-01

    The trumpet-tailed rat or degu (Octodon degus) is an established model to investigate the consequences of early stress on the development of emotional brain circuits and behavior. The aim of this study was to identify brain circuits, that respond to different stress conditions and to test if acute stress alters functional coupling of brain activity among prefrontal and limbic regions. Using functional imaging (2-Fluoro-deoxyglucose method) in 8-day-old male degu pups the following stress conditions were compared: (A) pups together with parents and siblings (control), (B) separation of the litter from the parents, (C) individual separation from parents and siblings, and (D) individual separation and presentation of maternal calls. Condition (B) significantly downregulated brain activity in the prefrontal cortex, hippocampus, nucleus accumbens (NAcc), and sensory areas compared to controls. Activity decrease was even more pronounced during condition (C), where, in contrast to all other regions, activity in the PAG was increased. Interestingly, brain activity in stress-associated brain regions such as the amygdala and habenula was not affected. In condition (D) maternal vocalizations “reactivated” brain activity in the cingulate and precentral medial cortex, NAcc, and striatum and in sensory areas. In contrast, reduced activity was measured in the prelimbic and infralimbic cortex (IL) and in the hippocampus and amygdala. Correlation analysis revealed complex, region- and situation-specific changes of interregional functional coupling among prefrontal and limbic brain regions during stress exposure. We show here for the first time that early life stress results in a widespread reduction of brain activity in the infant brain and changes interregional functional coupling. Moreover, maternal vocalizations can partly buffer stress-induced decrease in brain activity in some regions and evoked very different functional coupling patterns compared to the three other

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

    PubMed

    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

  1. 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

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

    PubMed Central

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

    2010-01-01

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

  3. 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. PMID:26481674

  4. Prefrontal and limbic resting state brain network functional connectivity differs between nicotine-dependent smokers and non-smoking controls

    PubMed Central

    Janes, Amy C.; Nickerson, Lisa; Frederick, Blaise deB.; Kaufman, Marc J.

    2012-01-01

    Background Brain dysfunction in prefrontal cortex (PFC) and dorsal striatum (DS) contributes to habitual drug use. These regions are constituents of brain networks thought to be involved in drug addiction. To investigate whether networks containing these regions differ between nicotine dependent female smokers and age-matched female non-smokers, we employed functional MRI (fMRI) at rest. Methods Data were processed with independent component analysis (ICA) to identify resting state networks (RSNs). We identified a subcortical limbic network and three discrete PFC networks: a medial prefrontal cortex (mPFC) network and right and left lateralized fronto-parietal networks common to all subjects. We then compared these RSNs between smokers and non-smokers using a dual regression approach. Results Smokers had greater coupling versus non-smokers between left fronto-parietal and mPFC networks. Smokers with the greatest mPFC-left fronto-parietal coupling had the most DS smoking cue reactivity as measured during an fMRI smoking cue reactivity paradigm. This may be important because the DS plays a critical role in maintaining drug-cue associations. Furthermore, subcortical limbic network amplitude was greater in smokers. Conclusions Our results suggest that prefrontal brain networks are more strongly coupled in smokers, which could facilitate drug-cue responding. Our data also are the first to document greater reward-related network fMRI amplitude in smokers. Our findings suggest that resting state PFC network interactions and limbic network amplitude can differentiate nicotine-dependent smokers from controls, and may serve as biomarkers for nicotine dependence severity and treatment efficacy. PMID:22459914

  5. Limbic encephalitis

    PubMed Central

    Mahawish, Karim; Teinert, Lynne; Cavanagh, Kathryn; Brennan, Joseph

    2014-01-01

    We present a case of paraneoplastic limbic encephalitis, describing the presenting features, diagnosis and management plan. Limbic encephalitis is one differential of rapidly progressive dementia. We describe a rational approach to the diagnosis of the patient with rapid cognitive decline. PMID:24891487

  6. 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. PMID:23777332

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

    PubMed Central

    Widge, Alik S.; Moritz, Chet T.

    2015-01-01

    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 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 (MFB), 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 prefrontal cortex 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. PMID:24608127

  8. 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.

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

    PubMed

    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

    2013-11-30

    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

  10. 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

  11. 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. PMID:23776761

  12. Multigenerational prenatal stress increases the coherence of brain signaling among cortico-striatal-limbic circuits in adult rats.

    PubMed

    Skelin, I; Needham, M A; Molina, L M; Metz, G A S; Gruber, A J

    2015-03-19

    Prenatal stress (PNS) is a significant risk factor for the development of psychopathology in adulthood such as anxiety, depression, schizophrenia and addiction. Animal models of PNS resemble many of the effects of PNS on humans and provide a means to study the accumulated effects of PNS over several generations on brain function. Here, we examined how mild PNS delivered during the third week in utero over four consecutive generations affects behavioral flexibility and functional signaling among cortical and limbic structures. These multi-generational prenatally stressed (MGPNS) rats were not impaired on an odor-cued reversal learning task as compared to control animals. Unilateral field potential (FP) recordings from the medial prefrontal cortex, basolateral amygdala, ventral hippocampus, and striatal territories revealed widespread differences in brain signaling between these groups during the odor sampling phase of the task. The FP power was significantly lower in most structures across most frequency bands in MGPNS animals, and the relative increase in power from baseline during the task was lower for the beta band (12-30Hz) in MGPNS animals as compared to controls. The coherence of FPs between brain regions, however, was much higher in MGPNS animals among all structures and for most frequency bands. We propose that this pattern of changes in brain signaling reflects a simplification of network processing, which is consistent with reports of reduced spine density and dendritic complexity in the brains of animals receiving PNS. Our data support the proposal that recurrent ancestral stress leads to adaptations in the brain, and that these may confer adaptive behavior in some circumstances as compared to single-generation PNS. PMID:25595989

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

    PubMed

    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

  14. 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

  15. 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.

  16. 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

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

    PubMed

    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

  18. 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

    2016-01-01

    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

  19. 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

  20. 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. PMID:26774005

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

    PubMed

    Walters, Glenn D; Kiehl, Kent A

    2015-12-15

    The purpose of this study was to determine whether scores on two temperament dimensions (fearlessness and disinhibition) correlated differentially with gray matter volumes in two limbic regions (amygdala and hippocampus). It was predicted that the fearlessness dimension would correlate with low gray matter volumes in the amygdala and the disinhibition dimension would correlate with low gray matter volumes in the hippocampus after controlling for age, IQ, regular substance use, and total brain volume. Participants were 191 male adolescents (age range=13-19 years) incarcerated in a maximum-security juvenile facility. Structural magnetic resonance imaging (MRI) analysis of the limbic and paralimbic regions of the brain was conducted. The temperament dimensions were estimated with items from the Psychopathy Checklist: Youth Version (PCL: YV: Forth et al., 2003). Analyses showed that the fearlessness dimension correlated negatively with gray matter volumes in the amygdala and the disinhibition dimension correlated negatively with gray matter volumes in the hippocampus but not vice versa. These findings provide preliminary support for the construct validity of the fearlessness and disinhibition temperament dimensions and offer confirmatory evidence for involvement of the amygdala and hippocampus in fear conditioning and behavioral inhibition, respectively. PMID:26363777

  2. 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

  3. 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

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

    PubMed Central

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

    2014-01-01

    Repeated Δ9-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 [35S]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. PMID:25093286

  5. Impaired Autonomic Responses to Emotional Stimuli in Autoimmune Limbic Encephalitis

    PubMed Central

    Schröder, Olga; Schriewer, Elisabeth; Golombeck, Kristin S.; Kürten, Julia; Lohmann, Hubertus; Schwindt, Wolfram; Wiendl, Heinz; Bruchmann, Maximilian; Melzer, Nico; Straube, Thomas

    2015-01-01

    Limbic encephalitis (LE) is an autoimmune-mediated disorder that affects structures of the limbic system, in particular, the amygdala. The amygdala constitutes a brain area substantial for processing of emotional, especially fear-related signals. The amygdala is also involved in neuroendocrine and autonomic functions, including skin conductance responses (SCRs) to emotionally arousing stimuli. This study investigates behavioral and autonomic responses to discrete emotion evoking and neutral film clips in a patient suffering from LE associated with contactin-associated protein-2 (CASPR2) antibodies as compared to a healthy control group. Results show a lack of SCRs in the patient while watching the film clips, with significant differences compared to healthy controls in the case of fear-inducing videos. There was no comparable impairment in behavioral data (emotion report, valence, and arousal ratings). The results point to a defective modulation of sympathetic responses during emotional stimulation in patients with LE, probably due to impaired functioning of the amygdala. PMID:26648907

  6. [A case report of recurrent limbic encephalitis caused by an enterovirus infection].

    PubMed

    Hokezu, Youichi; Hashiguchi, Yoshiya; Satake, Marie; Hosoya, Mitsuaki

    2004-03-01

    We reported a 28-year-old woman with recurrent focal encephalitis caused by an enterovirus infection. She showed convulsions, abnormal behavior, and consciousness disturbance on the first admission to our hospital in July 1998. A CSF study revealed lymphocyte-dominant pleocytosis (17/microl), and brain MRI revealed high signal intensity in the bilateral limbic system including the hippocampus. We treated her with acyclovir and steroid pulse therapy based on a diagnosis of limbic encephalitis. After that, her symptoms gradually disappeared without any sequelae. She became aware of memory disturbance at the end of April 2001. She was admitted to our hospital because of generalized convulsions on 2 May 2001. Her body temperature was 37.3 degrees C. Her consciousness was disturbed (Japan coma scale 2), but there was no nuchal rigidity. A CSF study failed to reveal pleocytosis (cell count, 2/microl). Brain MRI revealed a bilateral high signal intensity area in the limbic system. Her symptoms gradually improved, but the mild memory disturbance persisted on her discharge. An immunological study revealed no abnormality in either humoral or cell immunity. RT-PCR revealed enterovirus RNA in CSF samples obtained on 1 July 1998, 3 May 2001, and 25 July 2001. We diagnosed her as having recurrent limbic encephalitis caused by an enterovirus infection. This is the first report of recurrent limbic encepalitis caused by enterovirus infection in an host with an undetected defect of immune system. PMID:15233268

  7. Limbic system (image)

    MedlinePlus

    ... structures which govern emotions and behavior. The limbic system, and in particular the hippocampus and amygdala, is involved in the formation of long-term memory, and is closely associated with the olfactory structures ( ...

  8. Amygdala kindling disrupts trace and delay fear conditioning with parallel changes in Fos protein expression throughout the limbic brain.

    PubMed

    Botterill, J J; Fournier, N M; Guskjolen, A J; Lussier, A L; Marks, W N; Kalynchuk, L E

    2014-04-18

    Amygdala kindling is well known to increase unconditioned fear and anxiety. However, relatively little is known about whether this form of kindling causes functional changes within the neural circuitry that mediates fear learning and the retrieval of fear memories. To address this issue, we examined the effect of short- (i.e., 30 stimulations) and long-term (i.e., 99 stimulations) amygdala kindling in rats on trace and delay fear conditioning, which are aversive learning tasks that rely predominantly on the hippocampus and amygdala, respectively. After memory retrieval, we analyzed the pattern of neural activity with Fos, the protein product of the immediate early gene c-fos. We found that kindling had no effect on acquisition of the trace fear conditioning task but it did selectively impair retrieval of this fear memory. In contrast, kindling disrupted both acquisition and retrieval of fear memory in the delay fear conditioning task. We also found that kindling-induced impairments in memory retrieval were accompanied by decreased Fos expression in several subregions of the hippocampus, parahippocampus, and amygdala. Interestingly, decreased freezing in the trace conditioning task was significantly correlated with dampened Fos expression in hippocampal and parahippocampal regions whereas decreased freezing in the delay conditioning task was significantly correlated with dampened Fos expression in hippocampal, parahippocampal, and amygdaloid circuits. Overall, these results suggest that amygdala kindling promotes functional changes in brain regions involved in specific types of fear learning and memory. PMID:24486965

  9. Impaired limbic gamma oscillatory synchrony during anxiety-related behavior in a genetic mouse model of bipolar mania

    PubMed Central

    Dzirasa, Kafui; McGarity, DeAnna L.; Bhattacharya, Anirban; Kumar, Sunil; Takahashi, Joseph S.; Dunson, David; McClung, Colleen A.; Nicolelis, Miguel A. L.

    2011-01-01

    Alterations in anxiety-related processing are observed across many neuropsychiatric disorders including bipolar disorder. Though polymorphisms in a number of circadian genes confer risk for this disorder, little remains known about how changes in circadian gene function disrupt brain circuits critical for anxiety-related processing. Here we characterize neurophysiological activity simultaneously across five limbic brain areas (nucleus accumbens, amygdala, prelimbic cortex, ventral hippocampus, and ventral tegmental area) as wild-type (WT) mice and mice with a mutation in the circadian gene, CLOCK (Clock-Δ19 mice), perform an elevated zero-maze task. In WT mice, basal limbic gamma oscillatory synchrony observed prior to task performance predicted future anxiety-related behaviors. Additionally, dynamic changes in limbic gamma oscillatory synchrony were observed based on the position of WT mice on the zero-maze. Clock-Δ19 mice, which displayed an increased propensity to enter the open section of the elevated maze, showed profound deficits in these anxiety-related circuit processes. Thus, our findings link the anxiety-related behavioral deficits observed in Clock-Δ19 mice with dysfunctional gamma oscillatory tuning across limbic circuits, and suggest that alterations in limbic oscillatory circuit function induced by circadian gene polymorphisms may contribute to the behavioral manifestations seen in bipolar mania. PMID:21525286

  10. 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

  11. 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. PMID:25146309

  12. 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.

  13. Brain areas involved in the acupuncture treatment of AD model rats: a PET study

    PubMed Central

    2014-01-01

    Background Acupuncture may effectively treat certain symptoms of Alzheimer’s disease (AD). Although several studies have used functional brain imaging to investigate the mechanisms of acupuncture treatment on AD, these mechanisms are still poorly understood. We therefore further explored the mechanism by which needling at ST36 may have a therapeutic effect in a rat AD model. Methods A total of 80 healthy Wistar rats were divided into healthy control (n = 15) and pre-model (n = 65) groups. After inducing AD-like disease, a total of 45 AD model rats were randomly divided into three groups: the model group (n = 15), the sham-point group (n = 15), and the ST36 group (n = 15). The above three groups underwent PET scanning. PET images were processed with SPM2. Results The brain areas that were activated in the sham-point group relative to the model group were primarily centred on the bilateral limbic system, the right frontal lobe, and the striatum, whereas the activated areas in the ST36 group were primarily centred on the bilateral limbic system (pyriform cortex), the bilateral temporal lobe (olfactory cortex), the right amygdala and the right hippocampus. Compared with the sham-point group, the ST36 group showed greater activation in the bilateral amygdalae and the left temporal lobe. Conclusion We concluded that needling at a sham point or ST36 can increase blood perfusion and glycol metabolism in certain brain areas, and thus may have a positive influence on the cognition of AD patients. PMID:24886495

  14. Rapid increase of Nurr1 mRNA expression in limbic and cortical brain structures related to coping with depression-like behavior in mice.

    PubMed

    Rojas, Patricia; Joodmardi, Eliza; Perlmann, Thomas; Ogren, Sven Ove

    2010-08-01

    The immediate-early gene Nurr1 is a member of the inducible orphan nuclear receptor family. Nurr1 is essential to the differentiation, maturation, and maintenance of midbrain dopaminergic neurons and is expressed in different brain regions. We have reported that adult mice with reduced Nurr1 expression displayed an increase in immobility response to acute stress. These mice were also deficient in the retention of emotional memory. Thus, Nurr1 expression seems to be relevant to normal cognitive processes. To investigate the response of Nurr1 to a stress stimulus, Nurr1 mRNA expression was examined by in situ hybridization in adult mice using a depression-like behavior paradigm, the forced swim test. The Nurr1 gene was rapidly and widely up-regulated throughout the brain, including cortical areas (i.e., prefrontal cortex, primary and secondary visual cortex, primary auditory cortex, and secondary somatosensory cortex), hippocampus (dentate gyrus, CA1, CA2, and CA3), and midbrain (substantia nigra pars compacta and ventral tegmental area) at 30 min and 3 hr after the forced swim test. Dopamine content was reduced in prefrontal cortex and midbrain following swim stress. These results suggest that the increase in Nurr1 expression might be a compensatory mechanism to counteract the changes in forebrain dopamine transmission in coping with acute stress. PMID:20175204

  15. 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.

  16. Mapping of language brain areas in patients with brain tumors.

    PubMed

    Hyder, Rasha; Kamel, Nidal; Boon, Tang Tong; Reza, Faruque

    2015-08-01

    Language cortex in the human brain shows high variability among normal individuals and may exhibit a considerable shift from its original position due to tumor growth. Mapping the precise location of language areas is important before surgery to avoid postoperative language deficits. In this paper, the Magnetoencephalography (MEG) recording and the MRI scanning of six brain tumorous subjects are used to localize the language specific areas. MEG recordings were performed during two silent reading tasks; silent word reading and silent picture naming. MEG source imaging is performed using distributed source modeling technique called CLARA ("Classical LORETA Analysis Recursively Applied"). Estimated MEG sources are overlaid on individual MRI of each patient to improve interpretation of MEG source imaging results. The results show successful identification of the essential language areas and clear definition of the time course of neural activation connecting them. PMID:26736340

  17. Brain areas activated by uncertain reward-based decision-making in healthy volunteers

    PubMed Central

    Guo, Zongjun; Chen, Juan; Liu, Shien; Li, Yuhuan; Sun, Bo; Gao, Zhenbo

    2013-01-01

    Reward-based decision-making has been found to activate several brain areas, including the ventrolateral prefrontal lobe, orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mesolimbic dopaminergic system. In this study, we observed brain areas activated under three degrees of uncertainty in a reward-based decision-making task (certain, risky, and ambiguous). The tasks were presented using a brain function audiovisual stimulation system. We conducted brain scans of 15 healthy volunteers using a 3.0T magnetic resonance scanner. We used SPM8 to analyze the location and intensity of activation during the reward-based decision-making task, with respect to the three conditions. We found that the orbitofrontal cortex was activated in the certain reward condition, while the prefrontal cortex, precentral gyrus, occipital visual cortex, inferior parietal lobe, cerebellar posterior lobe, middle temporal gyrus, inferior temporal gyrus, limbic lobe, and midbrain were activated during the ‘risk’ condition. The prefrontal cortex, temporal pole, inferior temporal gyrus, occipital visual cortex, and cerebellar posterior lobe were activated during ambiguous decision-making. The ventrolateral prefrontal lobe, frontal pole of the prefrontal lobe, orbitofrontal cortex, precentral gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus, inferior parietal lobule, and cerebellar posterior lobe exhibited greater activation in the ‘risk’ than in the ‘certain’ condition (P < 0.05). The frontal pole and dorsolateral region of the prefrontal lobe, as well as the cerebellar posterior lobe, showed significantly greater activation in the ‘ambiguous’ condition compared to the ‘risk’ condition (P < 0.05). The prefrontal lobe, occipital lobe, parietal lobe, temporal lobe, limbic lobe, midbrain, and posterior lobe of the cerebellum were activated during decision-making about uncertain rewards. Thus, we observed different levels and regions of

  18. 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

  19. Heritability of the limbic networks.

    PubMed

    Budisavljevic, Sanja; 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

    2016-05-01

    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

  20. Electroencephalographic Evaluation for Early Diagnosis of Limbic Encephalitis.

    PubMed

    Pessa, Maria Elena; Janes, Francesco; Gigli, Gian Luigi

    2016-07-01

    Limbic encephalitis (LE) is an inflammation of structures of limbic system. It may be an autoimmune disease or secondary to a neoplasia. Onset is subacute within a few weeks and clinical presentation is characterized by behavioral changes, psychiatric symptoms, short-term memory loss, and epileptic seizures. Diagnosis is typically set after a magnetic resonance imaging (MRI) scan, revealing hyperintensity in limbic structures on T2, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) sequences or detection of antineuronal antibodies; EEG aspecific alterations on temporal areas usually match with MRI and laboratory findings. Specific diagnostic criteria are still under debate. We describe a case presenting with EEG alterations before MRI ones.A 36-year-old woman came to our attention for a first generalized tonic-clonic seizure, several episodes of likely epigastric auras and memory loss. Her clinical history was unremarkable. Neurological examination and brain MRI with gadolinium were normal. Electroencephalographic (EEG) recordings showed theta activity and sharp elements in frontotemporal regions. Therapy with levetiracetam 1000 mg/day was started, but she had another generalized seizure and episodes of epigastric auras increased to 10 per day. After 2 months, another cerebral MRI revealed areas of swelling and signal alteration in deep left temporal areas, especially in hippocampal and parahippocampal gyrus. A spectroscopic evaluation revealed decreased N-acetyl aspartate peak and increased choline and myo-inositol peaks in left frontotemporal areas. These findings were consistent with LE. Cerebrospinal fluid (CSF) analysis was normal; viral serology and onconeuronal antibodies on CSF and blood were negative. Patient was treated with high-dosage steroids, with improvement in memory, epileptic seizures and auras. A third MRI revealed no signal alterations.In conclusion, the clinical picture initially did not meet accepted diagnostic

  1. Brain areas in abyssal demersal fishes.

    PubMed

    Wagner, H J

    2001-06-01

    Four areas of the brain which receive primary projections from chemical senses ([1] olfactory bulb, [2] gustatory area including facial and vagal lobes), the eye ([3] optic tectum), and mechanosensory, and-hair-cell based systems i.e. the lateral line, vestibular and auditory systems ([4] trigeminal and octavolateral regions) have been studied and relative size differences used to make deductions on the sensory preferences of 35 fish species living on or near the bottom of the deep sea. Furthermore the relative volumes of the telencephalon and the corpus cerebelli were determined. Two evaluation modes were applied: (1) the relative mean of each system was calculated and species with above-average areas identified; (2) a cluster analysis established multivariate correlations among the sensory systems. The diversity of sensory brain areas in this population of fish suggests that the benthic and epibenthic environment of the abyss presents a rich sensory environment. Vision seems to be the single most important sense suggesting the presence of relevant bioluminescent stimuli. However, in combination the chemical senses, smell and taste, surpass the visual system; most prominent among them is olfaction. The trigeminal/octavolateral area indicating the role of lateral line input and possibly audition is also well represented, but only in association with other sensory modalities. A large volume telencephalon was often observed in combination with a prominent olfactory system, whereas cerebella of unusually large sizes occurred in species with above-average visual, hair-cell based, but also olfactory systems, confirming their role as multimodal sensorimotor coordination centers. In several species the predictions derived from the volumetric brain analyses were confirmed by earlier observations of stomach content and data obtained by baited cameras. PMID:11713385

  2. Responses of Limbic and Extrapyramidal Substance P Systems to Nicotine Treatment

    PubMed Central

    Alburges, Mario E.; Frankel, Paul S.; Hoonakker, Amanda J.; Hanson, Glen R.

    2009-01-01

    Rationale Neuropeptides are linked to the psychopathology of stimulants of abuse, principally through dopamine mechanisms. Substance P (SP) is one of these neuropeptides and is associated with both limbic and extrapyramidal dopaminergic pathways and likely contributes to the pharmacology of these stimulants. The effects of nicotine on these dopamine systems has also been extensively studied, however, its effects on the associated SP pathways, have received little attention. Objectives In the present study, we elucidated the effects of nicotine treatment on limbic and extrapyramidal SP systems by measuring changes in associated SP tissue concentrations. Materials and methods Male Sprague-Dawley rats received (±) nicotine 4.0 mg/kg/day (0.8 mg/kg, intraperitoneally; five injections at 2-h intervals) in the presence or absence of selective dopamine D1 and D2 receptor antagonists or a nonselective nicotinic acetylcholine receptor antagonist. Results The nicotine treatment significantly but temporarily decreased substance P-like immunoreactivity (SPLI) content in the ventral tegmental area (VTA) and substantia nigra 12–18 h after drug exposure. The nicotine-mediated changes in SPLI were selectively blocked by pretreatment with mecamylamine as well as a dopamine D1, D2, or both receptor antagonists. Other brain areas that also selectively demonstrated nicotine-related declines in SPLI content included prefrontal cortex, the nucleus accumbens shell and the very posterior caudate. Conclusions These findings indicate that some limbic and basal ganglia SP systems are significantly affected by exposure to nicotine through processes mediated by nicotinic and dopaminergic receptors, suggesting a role for SP pathways in nicotine’s limbic and extrapyramidal effects. PMID:18773198

  3. 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. PMID:20599363

  4. 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. PMID:23916832

  5. 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. PMID:24514569

  6. 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…

  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. Effects of botulinum toxin type A facial injection on monoamines and their metabolites in sensory, limbic and motor brain regions in rats.

    PubMed

    Ibragić, S; Matak, I; Dračić, A; Smajlović, A; Muminović, M; Proft, F; Sofić, E; Lacković, Z; Riederer, P

    2016-03-23

    Despite its toxicity, botulinum neurotoxin type A (BTX-A) is a valuable therapeutic agent for several motor, autonomic and pain disorders. Numerous studies have described its peripheral as well as central effects. Using reversed-phase High Performance Liquid Chromatography with Electrochemical Detection (HPLC-ED) and gradient elution, we quantified the concentrations of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in 10 brain regions, ipsilateral and contralateral from the site of unilateral BTX-A administration (5U/kg) into the rat whisker pad. In regions associated with nociception and pain processing we also examined possible BTX-A effects in combination with formalin-induced inflammatory orofacial pain. The dominant BTX-A effects on the monoamines and their metabolites were insignificant. The only significant increase caused by BTX-A alone was that of NA in striatum and serotonin in hypothalamus. While antinociceptive effects of BTX-A are most probably not related to central monoamine concentrations, the localized increased NA and 5-HT concentrations might play a role in reported BTX-A efficacy for the treatment of depression. PMID:26876447

  9. A temperament for learning: The limbic system and myelomeningocele

    PubMed Central

    Vachha, Behroze; Adams, Richard C

    2004-01-01

    This article was the winner of the triennial Casey Holter Memorial Prize awarded by the Society for Research into Hydrocephalus and Spina Bifida, 2004. Abstract This essay explores the link between the limbic/hypothalamic systems within the complex conditions of hydrocephalus and myelomeningocele. Acknowledging the neuroanatomical and neuroendocrine risks inherent in the developing brains of these individuals, we focus on the converging components of temperament, cognition, and language. PMID:15679940

  10. Auditory-limbic interactions in chronic tinnitus: Challenges for neuroimaging research.

    PubMed

    Leaver, Amber M; Seydell-Greenwald, Anna; Rauschecker, Josef P

    2016-04-01

    Tinnitus is a widespread auditory disorder affecting approximately 10-15% of the population, often with debilitating consequences. Although tinnitus commonly begins with damage to the auditory system due to loud-noise exposure, aging, or other etiologies, the exact neurophysiological basis of chronic tinnitus remains unknown. Many researchers point to a central auditory origin of tinnitus; however, a growing body of evidence also implicates other brain regions, including the limbic system. Correspondingly, we and others have proposed models of tinnitus in which the limbic and auditory systems both play critical roles and interact with one another. Specifically, we argue that damage to the auditory system generates an initial tinnitus signal, consistent with previous research. In our model, this "transient" tinnitus is suppressed when a limbic frontostriatal network, comprised of ventromedial prefrontal cortex and ventral striatum, successfully modulates thalamocortical transmission in the auditory system. Thus, in chronic tinnitus, limbic-system damage and resulting inefficiency of auditory-limbic interactions prevents proper compensation of the tinnitus signal. Neuroimaging studies utilizing connectivity methods like resting-state fMRI and diffusion MRI continue to uncover tinnitus-related anomalies throughout auditory, limbic, and other brain systems. However, directly assessing interactions between these brain regions and networks has proved to be more challenging. Here, we review existing empirical support for models of tinnitus stressing a critical role for involvement of "non-auditory" structures in tinnitus pathophysiology, and discuss the possible impact of newly refined connectivity techniques from neuroimaging on tinnitus research. PMID:26299843

  11. Limbic circuitry of the midline thalamus.

    PubMed

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

    2015-07-01

    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

  12. fMRI evidence of degeneration-induced neuropathic pain in diabetes: enhanced limbic and striatal activations.

    PubMed

    Tseng, Ming-Tsung; Chiang, Ming-Chang; Chao, Chi-Chao; Tseng, Wen-Yih I; Hsieh, Sung-Tsang

    2013-10-01

    Persistent neuropathic pain due to peripheral nerve degeneration in diabetes is a stressful symptom; however, the underlying neural substrates remain elusive. This study attempted to explore neuroanatomical substrates of thermal hyperalgesia and burning pain in a diabetic cohort due to pathologically proven cutaneous nerve degeneration (the painful group). By applying noxious 44°C heat stimuli to the right foot to provoke neuropathic pain symptoms, brain activation patterns were compared with those of healthy control subjects and patients with a similar degree of cutaneous nerve degeneration but without pain (the painless group). Psychophysical results showed enhanced affective pain ratings in the painful group. After eliminating the influence of different pain intensity ratings on cerebral responses, the painful group displayed augmented responses in the limbic and striatal structures, including the perigenual anterior cingulate cortex (ACC), superior frontal gyrus, medial thalamus, anterior insular cortex, lentiform nucleus (LN), and premotor area. Among these regions, blood oxygen level-dependent (BOLD) signals in the ACC and LN were correlated with pain ratings to thermal stimulations in the painful group. Furthermore, activation maps of a simple regression analysis as well as a region of interest analysis revealed that responses in these limbic and striatal circuits paralleled the duration of neuropathic pain. However, in the painless group, BOLD signals in the primary somatosensory cortex and ACC were reduced. These results suggest that enhanced limbic and striatal activations underlie maladaptive responses after cutaneous nerve degeneration, which contributed to the development and maintenance of burning pain and thermal hyperalgesia in diabetes. PMID:22522975

  13. Effects of NMDA-receptor antagonist treatment on c-fos expression in rat brain areas implicated in schizophrenia.

    PubMed

    Väisänen, Jussi; Ihalainen, Jouni; Tanila, Heikki; Castrén, Eero

    2004-12-01

    1. The noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists produce behavioral responses that closely resemble both positive and negative symptoms of schizophrenia. These drugs also induce excitatory and neurotoxic effects in limbic cortical areas. 2. We have here mapped the brain areas which show increased activity in response to noncompetitive NMDA-receptor antagonist administration concentrating especially to those brain areas that have been suggested to be relevant in the pathophysiology of schizophrenia. 3. Rats were treated intraperitoneally with a NMDA-receptor antagonist MK801 and activation of brain areas was detected by monitoring the expression of c-fos mRNA by using in situ hybridization. 4. MK801 induced c-fos mRNA expression of in the retrosplenial, entorhinal, and prefrontal cortices. Lower c-fos expression was observed in the layer IV of the parietal and frontal cortex. In the thalamus, c-fos mRNA expression was detected in the midline nuclei and in the reticular nucleus but not in the dorsomedial nucleus. In addition, c-fos mRNA was expressed in the anterior olfactory nucleus, the ventral tegmental area, and in cerebellar granule neurons. 5. NMDA-receptor antagonist ketamine increased dopamine release in the parietal cortex, in the region where NMDA-receptor antagonist increased c-fos mRNA expression. 6. Thus, the psychotropic NMDA-receptor antagonist induced c-fos mRNA expression in most, but not all, brain areas implicated in the pathophysiology of schizophrenia. The high spatial resolution of in situ hybridization may help to define regions of interest for human imaging studies. PMID:15672679

  14. Scientists Zero in On Brain Area Linked to 'Parkinson's Gait'

    MedlinePlus

    ... Scientists Zero in on Brain Area Linked to 'Parkinson's Gait' Discovery could lead to new treatments for ... play a role in walking difficulties that afflict Parkinson's disease patients, new research suggests. The prefrontal cortex ...

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

    PubMed Central

    Chang, Guo-Qing; Karatayev, Olga; Barson, Jessica R.; Liang, Sherry C.; Leibowitz, Sarah F.

    2014-01-01

    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 five 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

  16. 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

  17. Cortico-limbic-striatal contribution after response and reversal learning: a metabolic mapping study.

    PubMed

    Fidalgo, Camino; Conejo, N M; González-Pardo, Héctor; Arias, J L

    2011-01-12

    Learning of arbitrary stimulus-response associations is an adaptive behavior essential for species survival in an ever-changing environment. Particular subdivisions of the striatum have been shown to be critical for both motor-response learning and reversal learning. However, recent evidence suggests that different cortical and subcortical brain regions may be involved in response learning, a kind of learning more complex than previously thought. In fact, many brain regions subserving response learning seem to be also related to reversal learning, traditionally ascribed to the prefrontal cortex. The present study examined the role of different subdivisions of the rat prefrontal cortex, striatum, amygdala and the ventral tegmental area on both response and reversal learning evaluated in the water T-maze. Increased neuronal metabolic activity, as measured by cytochrome oxidase (CO) histochemistry, was found in most brain regions after training rats in a response learning task as compared to yoked controls. Reversal learning was associated with a return to baseline CO activity levels except for the orbitofrontal cortex and the ventral tegmental area. Analysis of functional connectivity among brain regions showed significant correlations in CO activity between particular cortical and striatal subdivisions in the reversal learning group. These findings suggest that the interaction of specific frontal and subcortical regions is required for reversal but not for response learning. However, our findings support the involvement of a cortico-limbic-striatal circuit in both types of learning. PMID:21036158

  18. Transient phonemic paraphasia by bilateral hippocampus lesion in a case of limbic encephalitis

    PubMed Central

    Kishi, Masahiko; Sakakibara, Ryuji; Ogata, Takeshi; Ogawa, Emina

    2010-01-01

    Although the hippocampus has not typically been identified as part of the language and aphasia circuit, recent evidence suggests that the hippocampus is closely related to naming, word priming, and anomic aphasia. A 59-year old woman with limbic encephalitis of possible autoimmune etiology, after recovery of consciousness, presented with severe memory impairment in both anterograde and retrograde modalities, episodes of fear, hallucination and convulsion, and transient fluent, phonemic paraphasia, together with small sharp waves diffusely by EEG. Brain MRI revealed bilateral symmetric, discrete lesions in the body to the infundibulum of the hippocampus. The transient phonemic paraphasia noted in our patient may have been a result of primary damage in the hippocampus and its fiber connection to the Wernicke's area or secondary partial status epilepticus that might have originated in the hippocampus. PMID:21577344

  19. 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)

  20. 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)

  1. 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. PMID:26290660

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

    PubMed Central

    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. PMID:26290660

  3. A Brain Area for Visual Numerals

    PubMed Central

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

    2014-01-01

    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. PMID:23595729

  4. 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. PMID:18640279

  5. 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. PMID:26663825

  6. Unstable Prefrontal Response to Emotional Conflict and Activation of Lower Limbic Structures and Brainstem in Remitted Panic Disorder

    PubMed Central

    Chechko, Natalya; Wehrle, Renate; Erhardt, Angelika; Holsboer, Florian; Czisch, Michael; Sämann, Philipp G.

    2009-01-01

    Background The neural mechanisms of panic disorder (PD) are only incompletely understood. Higher sensitivity of patients to unspecific fear cues and similarities to conditioned fear suggest involvement of lower limbic and brainstem structures. We investigated if emotion perception is altered in remitted PD as a trait feature. Methodology/Principal Findings We used blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study neural and behavioural responses of 18 remitted PD patients and 18 healthy subjects to the emotional conflict paradigm that is based on the presentation of emotionally congruent and incongruent face/word pairs. We observed that patients showed stronger behavioural interference and lower adaptation to interference conflict. Overall performance in patients was slower but not less accurate. In the context of preceding congruence, stronger dorsal anterior cingulate cortex (dACC) activation during conflict detection was found in patients. In the context of preceding incongruence, controls expanded dACC activity and succeeded in reducing behavioural interference. In contrast, patients demonstrated a dropout of dACC and dorsomedial prefrontal cortex (dmPFC) recruitment but activation of the lower limbic areas (including right amygdala) and brainstem. Conclusions/Significance This study provides evidence that stimulus order in the presentation of emotional stimuli has a markedly larger influence on the brain's response in remitted PD than in controls, leading to abnormal responses of the dACC/dmPFC and lower limbic structures (including the amygdala) and brainstem. Processing of non-panic related emotional stimuli is disturbed in PD patients despite clinical remission. PMID:19462002

  7. 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

  8. Progressive limbic encephalopathy: Problems and prospects

    PubMed Central

    Chandra, Sadanandavalli Retnaswami; Seshadri, Roopa; Chikabasaviah, Yasha; Issac, Thomas Gregor

    2014-01-01

    Background: It was observed that a good number of patients presenting with psychiatric manifestations when investigated later because of unresponsiveness to treatment or late development of organic features turned out to be treatable limbic syndromes. Introduction: The aim of this study is to assess the patients presenting with new onset neuropsychiatric symptoms satisfying the criteria for probable limbic encephalitis. Patients and Methods: Patients referred to neurology department following a period of treatment for neuropsychiatric symptoms, which did not respond to conventional treatment were analyzed using Electroencephalography (EEG), magnetic resonance imaging, cerebrospinal fluid, screening for malignancy Vasculitic work-up, histopathology and autoantibody done when feasible. Results: There were 22 patients satisfying criteria for probable limbic encephalitis. Their mean age was 34.5 years. Symptoms varied from unexplained anxiety, panic and depression, lack of inhibition, wandering, incontinence, myoclonus, seizures and stroke like episodes. Three had systemic malignancy, 10 had chronic infection, one each with vasculitis, acute disseminated encephalomyelitis, Hashimoto encephalitis and two each with non-convulsive status, cryptogenic and Idiopathic inflammation. Conclusion: All patients who present with new onset neuropsychiatric symptoms need to be evaluated for sub-acute infections, inflammation, autoimmune limbic encephalitis and paraneoplastic syndrome. A repeated 20 minute EEG is a very effective screening tool to detect organicity. PMID:25024566

  9. 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. PMID:26577509

  10. 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

  11. 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. PMID:26876303

  12. Deep brain stimulation affects conditioned and unconditioned anxiety in different brain areas.

    PubMed

    van Dijk, A; Klanker, M; van Oorschot, N; Post, R; Hamelink, R; Feenstra, M G P; Denys, D

    2013-01-01

    Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive-compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of principal interest to understand which brain area is responsible for the anxiolytic effect and whether high-frequency stimulation of different areas differentially affect unconditioned (innate) and conditioned (learned) anxiety. In this study, we examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU)). The elevated plus maze was used to test the effect of stimulation on unconditioned anxiety, the Vogel conflict test for conditioned anxiety, and an activity test for general locomotor behaviour. We found different anxiolytic effects of stimulation in the five target areas. Stimulation of the CAU decreased both conditioned and unconditioned anxiety, while stimulation of the IC uniquely reduced conditioned anxiety. Remarkably, neither the accumbens nor the BNST stimulation affected conditioned or unconditioned anxiety. Locomotor activity increased with NAc core stimulation but decreased with the BNST. These findings suggest that (1) DBS may have a differential effect on unconditioned and conditioned anxiety depending on the stimulation area, and that (2) stimulation of the IC exclusively reduces conditioned anxiety. This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC. PMID:23900312

  13. Prelude to Passion: Limbic Activation by “Unseen” Drug and Sexual Cues

    PubMed Central

    Childress, Anna Rose; Ehrman, Ronald N.; Wang, Ze; Li, Yin; Sciortino, Nathan; Hakun, Jonathan; Jens, William; Suh, Jesse; Listerud, John; Marquez, Kathleen; Franklin, Teresa; Langleben, Daniel; Detre, John; O'Brien, Charles P.

    2008-01-01

    Background The human brain responds to recognizable signals for sex and for rewarding drugs of abuse by activation of limbic reward circuitry. Does the brain respond in similar way to such reward signals even when they are “unseen”, i.e., presented in a way that prevents their conscious recognition? Can the brain response to “unseen” reward cues predict the future affective response to recognizable versions of such cues, revealing a link between affective/motivational processes inside and outside awareness? Methodology/Principal Findings We exploited the fast temporal resolution of event-related functional magnetic resonance imaging (fMRI) to test the brain response to “unseen” (backward-masked) cocaine, sexual, aversive and neutral cues of 33 milliseconds duration in male cocaine patients (n = 22). Two days after scanning, the affective valence for visible versions of each cue type was determined using an affective bias (priming) task. We demonstrate, for the first time, limbic brain activation by “unseen” drug and sexual cues of only 33 msec duration. Importantly, increased activity in an large interconnected ventral pallidum/amygdala cluster to the “unseen” cocaine cues strongly predicted future positive affect to visible versions of the same cues in subsequent off-magnet testing, pointing both to the functional significance of the rapid brain response, and to shared brain substrates for appetitive motivation within and outside awareness. Conclusions/Significance These findings represent the first evidence that brain reward circuitry responds to drug and sexual cues presented outside awareness. The results underscore the sensitivity of the brain to “unseen” reward signals and may represent the brain's primordial signature for desire. The limbic brain response to reward cues outside awareness may represent a potential vulnerability in disorders (e.g., the addictions) for whom poorly-controlled appetitive motivation is a central feature

  14. Candidate gene associations with mood disorder, cognitive vulnerability, and fronto-limbic volumes

    PubMed Central

    Frazier, Thomas W; Youngstrom, Eric A; Frankel, Brian A; Zunta-Soares, Giovana B; Sanches, Marsal; Escamilla, Michael; Nielsen, David A; Soares, Jair C

    2014-01-01

    Background Four of the most consistently replicated variants associated with mood disorder occur in genes important for synaptic function: ANK3 (rs10994336), BDNF (rs6265), CACNA1C (rs1006737), and DGKH (rs1170191). Aims The present study examined associations between these candidates, mood disorder diagnoses, cognition, and fronto-limbic regions implicated in affect regulation. Methods and materials Participants included 128 individuals with bipolar disorder (33% male, Mean age = 38.5), 48 with major depressive disorder (29% male, Mean age = 40.4), and 149 healthy controls (35% male, Mean age = 36.5). Genotypes were determined by 5′-fluorogenic exonuclease assays (TaqMan®). Fronto-limbic volumes were obtained from high resolution brain images using Freesurfer. Chi-square analyses, bivariate correlations, and mediational models examined relationships between genetic variants, mood diagnoses, cognitive measures, and brain volumes. Results Carriers of the minor BDNF and ANK3 alleles showed nonsignificant trends toward protective association in controls relative to mood disorder patients (P = 0.047). CACNA1C minor allele carriers had larger bilateral caudate, insula, globus pallidus, frontal pole, and nucleus accumbens volumes (smallest r = 0.13, P = 0.043), and increased IQ (r = 0.18, P < 0.001). CACNA1C associations with brain volumes and IQ were independent; larger fronto-limbic volumes did not mediate increased IQ. Other candidate variants were not significantly associated with diagnoses, cognition, or fronto-limbic volumes. Discussion and conclusions CACNA1C may be associated with biological systems altered in mood disorder. Increases in fronto-limbic volumes and cognitive ability associated with CACNA1C minor allele genotypes are congruent with findings in healthy samples and may be a marker for increased risk for neuropsychiatric phenotypes. Even larger multimodal studies are needed to quantify the magnitude and specificity of genetic

  15. 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. PMID:27526187

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

    PubMed

    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

  17. 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

  18. Attachment style dimensions are associated with brain activity in response to gaze interaction.

    PubMed

    Cecchini, Marco; Iannoni, Maria Elena; Pandolfo, Anna Lucia; Aceto, Paola; Lai, Carlo

    2015-01-01

    Aim of the present study was to investigate the time course of brain processes involved in the visual perception of different gaze interactions in woman-child dyads and the association between attachment dimensions and brain activation during the presentation of gaze interactions. The hypothesis was that the woman avoidance will produce a greater activation of primary somatosensory and limbic areas. The attachment styles dimensions avoidant-related will be associated with fronto-limbic brain intensity during the convergence of gaze. Electroencephalogram (EEG) data were recorded using a 256-channel HydroCel Geodesic Sensor Net in 44 female subjects (age: 24 ± 2 years). Event-related potential (ERP) components and standardized low-resolution electromagnetic tomography (sLORETA) were analyzed. Participants were administered the attachment style questionnaire before EEG task. A lower P350 latency was found in the fronto-central montage in response to woman avoidance. sLORETA analysis showed a greater intensity of limbic and primary somatosensory areas in response to woman avoidance compared to the others gaze interactions. In response to convergence gaze, the confidence attachment dimension was negatively correlated with the intensities of the right temporal and limbic areas, and the relationships as secondary attachment dimension were positively correlated with the intensities of the bilateral frontal areas and of the left parietal area. PMID:25568957

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

    PubMed

    Lee, Tae-Ho; Telzer, Eva H

    2016-08-01

    Recent developmental brain imaging studies have demonstrated that negatively coupled prefrontal-limbic circuitry implicates the maturation of brain development in adolescents. Using resting-state functional magnetic resonance imaging (rs-fMRI) and independent component analysis (ICA), the present study examined functional network coupling between prefrontal and limbic systems and links to self-control and substance use onset in adolescents. Results suggest that negative network coupling (anti-correlated temporal dynamics) between the right fronto-parietal and limbic resting state networks is associated with greater self-control and later substance use onset in adolescents. These findings increase our understanding of the developmental importance of prefrontal-limbic circuitry for adolescent substance use at the resting-state network level. PMID:27344035

  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. PMID:21967727

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

    PubMed Central

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

    2014-01-01

    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. PMID:24478326

  2. 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. PMID:24478326

  3. Early Life Stress as an Influence on Limbic Epilepsy: An Hypothesis Whose Time has Come?

    PubMed Central

    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. PMID:19838325

  4. Effects of oxytocin and a derivative (Z-prolyl-D-leucine) on morphine tolerance/withdrawal are mediated by the limbic system.

    PubMed

    Kovács, G L; Izbéki, F; Horváth, Z; Telegdy, G

    1984-10-01

    Recent data indicate that the neurohypophyseal hormone oxytocin (OXT) and Z-prolyl-D-leucine (Z-Pro-D-Leu), a synthetic dipeptide derived from the C-terminal part of OXT, attenuate the development of tolerance to and dependence on morphine in the mouse. Biochemical and behavioral data raise the possibility that these effects of the peptides might be associated with their effects on the central nervous system and in particular on limbic brain structures. The present results confirm this hypothesis, since intracerebroventricular (i.c.v., 50 ng) and local (0.5 ng) injections of OXT and Z-Pro-D-Leu into the dorsal hippocampus and the mesolimbic nucleus accumbens attenuate morphine tolerance/dependence, similarly to systemic injections of these peptides in higher amounts (5-50 micrograms). Local injections of these peptides into other brain sites (e.g. the nucleus caudatus, ventral tegmental area and the external cortical surface) are without effect. Lesion of the nucleus accumbens by the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) completely prevents the effects of Z-Pro-D-Leu and partially those of OXT on morphine tolerance/dependence. The data point to the role of limbic structures as mediators of the effects of neuropeptides on morphine addiction. PMID:6542796

  5. Increased cortical-limbic anatomical network connectivity in major depression revealed by diffusion tensor imaging.

    PubMed

    Fang, Peng; Zeng, Ling-Li; Shen, Hui; Wang, Lubin; Li, Baojuan; Liu, Li; Hu, Dewen

    2012-01-01

    Magnetic resonance imaging studies have reported significant functional and structural differences between depressed patients and controls. Little attention has been given, however, to the abnormalities in anatomical connectivity in depressed patients. In the present study, we aim to investigate the alterations in connectivity of whole-brain anatomical networks in those suffering from major depression by using machine learning approaches. Brain anatomical networks were extracted from diffusion magnetic resonance images obtained from both 22 first-episode, treatment-naive adults with major depressive disorder and 26 matched healthy controls. Using machine learning approaches, we differentiated depressed patients from healthy controls based on their whole-brain anatomical connectivity patterns and identified the most discriminating features that represent between-group differences. Classification results showed that 91.7% (patients=86.4%, controls=96.2%; permutation test, p<0.0001) of subjects were correctly classified via leave-one-out cross-validation. Moreover, the strengths of all the most discriminating connections were increased in depressed patients relative to the controls, and these connections were primarily located within the cortical-limbic network, especially the frontal-limbic network. These results not only provide initial steps toward the development of neurobiological diagnostic markers for major depressive disorder, but also suggest that abnormal cortical-limbic anatomical networks may contribute to the anatomical basis of emotional dysregulation and cognitive impairments associated with this disease. PMID:23049910

  6. Effect of cocaine and sucrose withdrawal period on extinction behavior, cue-induced reinstatement, and protein levels of the dopamine transporter and tyrosine hydroxylase in limbic and cortical areas in rats.

    PubMed

    Grimm, J W; Shaham, Y; Hope, B T

    2002-09-01

    Lever pressing during tests for resistance to extinction and cue-induced reinstatement of cocaine seeking in rats progressively increases over the first 2 months of withdrawal. In the present report, we investigated the generality of these findings in rats trained to self-administer sucrose, a non-drug reinforcer. We also examined whether the time-dependent changes in cocaine seeking correlate with the levels of the dopamine transporter (DAT) and tyrosine hydroxylase (TH) proteins in the amygdala, nucleus accumbens, prefrontal cortex and orbitofrontal cortex. Rats were trained to self-administer cocaine (0.5 mg/kg/i.v. infusion) or 10% sucrose (0.2 ml/infusion into a liquid drop receptacle) for 10 days (6 h/day); each reward delivery was paired with a tone+light cue. Tests for cocaine seeking were conducted following 1 or 15 reward-free days. On the test day, rats were initially tested for resistance to extinction during 6-7 60-min extinction sessions in the absence of the tone-light cue, until they reached the extinction criterion of less than 15 responses/60 min. Subsequently, rats were tested for cue-induced reinstatement during a 60-min session in which each lever press led to a contingent presentation of the tone-light cue. Lever pressing during the tests for reward seeking was significantly greater on day 15 than on day 1 following withdrawal from both cocaine and sucrose self-administration training. The levels of DAT, but not TH, were greater in the prefrontal cortex of cocaine-trained rats than in sucrose-trained rats on both days 1 and 15 of withdrawal. The levels of DAT and TH in other brain areas were not altered following withdrawal from cocaine or sucrose self-administration. These data suggest that the withdrawal can modulate reward seeking of both drug and non-drug reinforcers, and that alterations in DAT and TH levels in the brain regions examined do not mediate this effect. PMID:12394414

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

    PubMed

    Keitel, Anne; Gross, Joachim

    2016-06-01

    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

  9. 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

  10. Decreased limbic and increased fronto-parietal connectivity in unmedicated patients with obsessive-compulsive disorder.

    PubMed

    Göttlich, Martin; Krämer, Ulrike M; Kordon, Andreas; Hohagen, Fritz; Zurowski, Bartosz

    2014-11-01

    Obsessive-compulsive disorder (OCD) is characterized by recurrent intrusive thoughts and ritualized, repetitive behaviors, or mental acts. Convergent experimental evidence from neuroimaging and neuropsychological studies supports an orbitofronto-striato-thalamo-cortical dysfunction in OCD. Moreover, an over excitability of the amygdala and over monitoring of thoughts and actions involving the anterior cingulate, frontal and parietal cortex has been proposed as aspects of pathophysiology in OCD. We chose a data driven, graph theoretical approach to investigate brain network organization in 17 unmedicated OCD patients and 19 controls using resting-state fMRI. OCD patients showed a decreased connectivity of the limbic network to several other brain networks: the basal ganglia network, the default mode network, and the executive/attention network. The connectivity within the limbic network was also found to be decreased in OCD patients compared to healthy controls. Furthermore, we found a stronger connectivity of brain regions within the executive/attention network in OCD patients. This effect was positively correlated with disease severity. The decreased connectivity of limbic regions (amygdala, hippocampus) may be related to several neurocognitive deficits observed in OCD patients involving implicit learning, emotion processing and expectation, and processing of reward and punishment. Limbic disconnection from fronto-parietal regions relevant for (re)-appraisal may explain why intrusive thoughts become and/or remain threatening to patients but not to healthy subjects. Hyperconnectivity within the executive/attention network might be related to OCD symptoms such as excessive monitoring of thoughts and behavior as a dysfunctional strategy to cope with threat and uncertainty. PMID:25044747

  11. 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.

  12. A case study of voltage-gated potassium channel antibody-related limbic encephalitis with PET/MRI findings

    PubMed Central

    Day, Brian K.; Eisenman, Lawrence; Black, Joseph; Maccotta, Luigi; Hogan, R. Edward

    2015-01-01

    Preclinical and clinical studies have demonstrated the significance of inflammation and autoantibodies in epilepsy, and the use of immunotherapies in certain situations has become an established practice. Temporal lobe epilepsy can follow paraneoplastic or nonparaneoplastic limbic encephalitis associated with antibodies directed against brain antigens. Here, we focus on a patient with worsening confusion and temporal lobe seizures despite treatment with antiepileptic medications. Serial brain MRIs did not conclusively reveal structural abnormalities, so the patient underwent brain PET/MRI to simultaneously evaluate brain structure and function, revealing bitemporal abnormalities. The patient was diagnosed with voltage-gated potassium channel antibody-related limbic encephalitis based on clinical presentation, imaging findings, and antibody testing. Treatment included the addition of a second antiepileptic agent and oral steroids. His seizures and cognitive deficits improved and stabilized. PMID:26106579

  13. 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.

  14. 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. PMID:25801500

  15. 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. PMID:26796690

  16. 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. PMID:19135805

  17. Retroductive reasoning in a proposed subtype of partial seizures, evoked by limbic "kindling".

    PubMed

    Pontius, A A

    1995-02-01

    This analysis provides a specific example of the generally applicable process of creative delineation of a novel pattern while searching for an explanatory hypothesis for puzzling observations. In so doing, the neglected retroductive form of inference or abduction was used. Central to such a process is the delineation of a specific "generative mechanism" capable of uniting and explaining heretofore unexplained phenomena. Herein the neurophysiologically known mechanism of limbic seizure "kindling" is offered as a unifying explanation for a dozen bizarre phenomena, proposed as a new subtype of partial seizures, "Limbic Psychotic Trigger Reaction." This new syndrome has been proposed over 15 years in 17 male social loners. Upon encounter with an individualized stimulus, which revived in memory prior moderately hurtful experiences, these men suddenly committed motiveless, unplanned acts with flat affect, transient psychosis and autonomic arousal, showing no quantitative impairment of consciousness and so without memory loss for their perplexing homicidal acts (13 cases), firesetting (3 cases), or bank robbery (1 case). Events occurred in three phases reminiscent of seizures: (1) aura-like puzzlement, (2) transient ictus with a limbic release of predatory or defensive aggression (circa 20 min.), and (3) postictal inefficient actions, implicating a transient frontal lobe system dysfunction secondary to the limbic hyperactivation. The 17 men were of diverse backgrounds, but all without history of prior violence or severe emotional trauma. Seven of 17 had some abnormal tests at some time during their lives and eight known histories of typically overlooked closed-brain injury. Brain damage may facilitate seizure "kindling" but has been traditionally observed in mammals and in a few humans without such damage. PMID:7770594

  18. Strongly reduced number of parvalbumin-immunoreactive projection neurons in the mammillary bodies in schizophrenia: further evidence for limbic neuropathology.

    PubMed

    Bernstein, Hans-Gert; Krause, Stephanie; Krell, Dieter; Dobrowolny, Henrik; Wolter, Marion; Stauch, Renate; Ranft, Karin; Danos, Peter; Jirikowski, Gustav F; Bogerts, Bernhard

    2007-01-01

    The mammillary bodies (MB) are important relay nuclei within limbic and extralimbic connections. They are known to play important roles in memory formation and are affected in alcoholism and vitamin B1 deficiency. Their strategic position linking temporo-limbic to cortico-thalamic brain structures make the MB a candidate brain structure for alterations in schizophrenia. We studied 15 postmortem brains of schizophrenics and 15 matched control brains. Brain sections were stained either with Heidenhain-Woelcke, glutamic acid decarboxylase (GAD), calretinin, or parvalbumin. We determined the volumes of the MB and performed cell countings using stereological principles and a computerized image analysis system. The volumes of MB do not differ between schizophrenics and controls. However, in schizophrenia the number of neurons as well as the resulting neuronal densities was significantly reduced on both sides (on left side by 38.9%, on right side by 22%). No changes were seen in the number of GAD-expressing or calretinin-containing neurons, whereas the number of parvalbumin-immunoreactive MB neurons was reduced by more than 50% in schizophrenia. This cell loss (as a result of developmental malformation and/or neurodegeneration) points to a prominent involvement of the MB in the pathomorphology of schizophrenia. Parvalbumin-immunoreactive GABAergic interneurons have been reported to be diminished in schizophrenia. However, in the MB parvalbumin labels a subpopulation of glutamate/aspartate-containing neurons projecting mainly to the anterior thalamus. Thus, our data provide new evidence for impaired limbic circuits in schizophrenia. PMID:17405923

  19. 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.

  20. PERVASIVE OLFACTORY IMPAIRMENT AFTER BILATERAL LIMBIC SYSTEM DESTRUCTION

    PubMed Central

    Tranel, Daniel; Welsh-Bohmer, Kathleen A.

    2012-01-01

    What pattern of brain damage could completely obliterate the sense of olfaction in humans? We had an opportunity to address this intriguing question in patient B., who has extensive bilateral damage to most of the limbic system, including the medial and lateral temporal lobes, orbital frontal cortex, insular cortex, anterior cingulate cortex, and basal forebrain, caused by herpes simplex encephalitis. The patient demonstrated profound impairments in odor identification and recognition. Moreover, he could not discriminate between olfactory stimuli and he had severe impairments in odor detection. Reliable stimulus detection was obtained only for solutions of the organic solvent acetone and highly concentrated solutions of ethanol. In contrast to the more circumscribed olfactory deficits demonstrated in patients with damage confined to either the temporal lobes or orbitofrontal cortex (which tend to involve odor identification but not odor detection), patient B. demonstrates a strikingly severe and complete anosmia. This contrast in olfactory abilities and deficits as a result of different anatomical pathology affords new insights into the neural substrates of olfactory processing in humans. PMID:22220560

  1. 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. PMID:27313873

  2. 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

  3. 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. PMID:25700996

  4. Investigation of LGI1 as the antigen in limbic encephalitis previously attributed to potassium channels: a case series

    PubMed Central

    Lai, Meizan; Huijbers, Maartje G M; Lancaster, Eric; Graus, Francesc; Bataller, Luis; Balice-Gordon, Rita; Cowell, John K; Dalmau, Josep

    2011-01-01

    Summary Background Voltage-gated potassium channels are thought to be the target of antibodies associated with limbic encephalitis. However, antibody testing using cells expressing voltage-gated potassium channels is negative; hence, we aimed to identify the real autoantigen associated with limbic encephalitis. Methods We analysed sera and CSF of 57 patients with limbic encephalitis and antibodies attributed to voltage-gated potassium channels and 148 control individuals who had other disorders with or without antibodies against voltage-gated potassium channels. Immunohistochemistry, immunoprecipitation, and mass spectrometry were used to characterise the antigen. An assay with HEK293 cells transfected with leucine-rich, glioma-inactivated 1 (LGI1) and disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) or ADAM23 was used as a serological test. The identity of the autoantigen was confirmed by immunoabsorption studies and immunostaining of Lgi1-null mice. Findings Immunoprecipitation and mass spectrometry analyses showed that antibodies from patients with limbic encephalitis previously attributed to voltage-gated potassium channels recognise LGI1, a neuronal secreted protein that interacts with presynaptic ADAM23 and postsynaptic ADAM22. Immunostaining of HEK293 cells transfected with LGI1 showed that sera or CSF from patients, but not those from control individuals, recognised LGI1. Co-transfection of LGI1 with its receptors, ADAM22 or ADAM23, changed the pattern of reactivity and improved detection. LGI1 was confirmed as the autoantigen by specific abrogation of reactivity of sera and CSF from patients after immunoabsorption with LGI1-expressing cells and by comparative immunostaining of wild-type and Lgi1-null mice, which showed selective lack of reactivity in brains of Lgi1-null mice. One patient with limbic encephalitis and antibodies against LGI1 also had antibodies against CASPR2, an autoantigen we identified in some patients with

  5. Clinico-pathological correlation in adenylate kinase 5 autoimmune limbic encephalitis.

    PubMed

    Ng, Adeline S L; Kramer, Joel; Centurion, Alejandro; Dalmau, Josep; Huang, Eric; Cotter, Jennifer A; Geschwind, Michael D

    2015-10-15

    Autoantibodies associated with autoimmune limbic encephalitis (ALE) have been well-characterized, with intracellular neuronal antibodies being less responsive to immunotherapy than antibodies to cell surface antigens. Adenylate kinase 5 (AK5) is a nucleoside monophosphate kinase vital for neuronal-specific metabolism and is located intracellularly in the cytosol and expressed exclusively in the brain. Antibodies to AK5 had been previously identified but were not known to be associated with human disease prior to the report of two patients with AK5-related ALE (Tuzun et al., 2007). We present the complete clinical picture for one of these patients and the first reported neuropathology for AK5 ALE. PMID:26439959

  6. 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. PMID:22209327

  7. Compromised Blood-Brain Barrier Competence in Remote Brain Areas in Ischemic Stroke Rats at Chronic Stage

    PubMed Central

    Garbuzova-Davis, Svitlana; Haller, Edward; Williams, Stephanie N.; Haim, Eithan D.; Tajiri, Naoki; Hernandez-Ontiveros, Diana G.; Frisina-Deyo, Aric; Boffeli, Sean M.; Sanberg, Paul R.; Borlongan, Cesario V.

    2014-01-01

    Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. PMID:24610730

  8. Dynamic Limbic Networks and Social Diversity in Vertebrates: From Neural Context to Neuromodulatory Patterning

    PubMed Central

    Goodson, James L.; Kabelik, David

    2009-01-01

    Vertebrate animals exhibit a spectacular diversity of social behaviors, yet a variety of basic social behavior processes are essential to all species. These include social signaling; discrimination of conspecifics and sexual partners; appetitive and consummatory sexual behaviors; aggression and dominance behaviors; and parental behaviors (the latter with rare exceptions). These behaviors are of fundamental importance and are regulated by an evolutionarily conserved, core social behavior network (SBN) of the limbic forebrain and midbrain. The SBN encodes social information in a highly dynamic, distributed manner, such that behavior is most strongly linked to the pattern of neural activity across the SBN, not the activity of single loci. Thus, shifts in the relative weighting of activity across SBN nodes can conceivably produce almost limitless variation in behavior, including diversity across species (as weighting is modified through evolution), across behavioral contexts (as weights change temporally) and across behavioral phenotypes (as weighting is specified through heritable and developmental processes). Individual neural loci may also express diverse relationships to behavior, depending upon temporal variations in their functional connectivity to other brain regions (“neural context”). We here review the basic properties of the SBN and show how behavioral variation relates to functional connectivity of the network, and discuss ways in which neuroendocrine factors adjust network activity to produce behavioral diversity. In addition to the actions of steroid hormones on SBN state, we examine the temporally plastic and evolutionarily labile properties of the nonapeptides (the vasopressin- and oxytocin-like neuropeptides), and show how variations in nonapeptide signaling within the SBN serve to promote behavioral diversity across social contexts, seasons, phenotypes and species. Although this diversity is daunting in its complexity, the search for common

  9. 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. PMID:25959040

  10. 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.

  11. 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

  12. 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

    2015-01-01

    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

  13. 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

  14. Sex differences of Gray Matter Morphology in Cortico-limbic-striatal Neural System in Major Depressive Disorder

    PubMed Central

    Kong, Lingtao; Chen, Kaiyuan; Womer, Fay; Jiang, Wenyan; Luo, Xingguang; Driesen, Naomi; Liu, Jie; Blumberg, Hilary; Tang, Yanqing; Xu, Ke; Wang, Fei

    2013-01-01

    Sex differences are observed in both epidemiological and clinical aspects of major depressive disorder (MDD). The cortico-limbic-striatal neural system, including the prefrontal cortex, amygdala, hippocampus, and striatum, have shown sexually dimorphic morphological features and have been implicated in the dysfunctional regulation of mood and emotion in MDD. In this study, we utilized a whole-brain, voxel-based approach to examine sex differences in the regional distribution of gray matter (GM) morphological abnormalities in medication-naïve participants with MDD. Participants included 29 medication-naïve individuals with MDD (16 females and 13 males) and 33 healthy controls (HC) (17 females and 16 males). Gray matter morphology of the cortico-limbic-striatal neural system was examined using voxel-based morphometry analyses of high-resolution structural magnetic resonance imaging scans. The main effect of diagnosis and interaction effect of diagnosis by sex on GM morphology were statistically significant (p<0.05, corrected) in the left ventral prefrontal cortex, right amygdala, right hippocampus and bilateral caudate when comparing the MDD and HC groups. Posthoc analyses showed that females with MDD had significant GM decreases in limbic regions (p<0.05, corrected), compared to female HC; while males with MDD demonstrated significant GM reduction in striatal regions, (p<0.05, corrected), compared to HC males. The observed sex-related patterns of abnormalities within the cortico-limbic-strial neural system, such as predominant prefrontal-limbic abnormalities in MDD females vs. predominant prefrontal-striatal abnormalities in MDD males, suggest differences in neural circuitry that may mediate sex differences in the clinical presentation of MDD and potential targets for sex-differentiated treatment of the disorder. PMID:23453566

  15. SVZ-derived newly generated neurons populate several olfactory and limbic forebrain regions

    PubMed Central

    Shapiro, Lee A.; Ng, Kwan; Zhou, Qun-Yong; Ribak, Charles E.

    2009-01-01

    Neurogenesis persists in several regions of the adult mammalian brain. Although the hippocampus and olfactory bulb are most commonly studied in the context of adult neurogenesis, there is an increasing body of evidence in support of neurogenesis occurring outside of these two regions. The current study expands upon previous data by showing newborn neurons with a mature phenotype are located in several olfactory and limbic structures outside of the hippocampus and olfactory bulb, where we previously described DCX/BrdU immature neurons. Notably, newborn neurons with a mature neuronal phenotype are found in the olfactory tubercles, anterior olfactory nuclei, tenia tecta, islands of Calleja, amygdala and lateral entorhinal cortex. The appearance of newborn neurons with a mature phenotype in these regions suggests that these structures are destinations, and that newborn neurons are not simply passing through these structures. In light of the increasing body of evidence for neurogenesis in these, and other olfactory, limbic and striatal structures, we hypothesize that brain regions displaying adult neurogenesis are functionally linked. PMID:18849007

  16. Surface area and cortical thickness descriptors reveal different attributes of the structural human brain networks.

    PubMed

    Sanabria-Diaz, Gretel; Melie-García, Lester; Iturria-Medina, Yasser; Alemán-Gómez, Yasser; Hernández-González, Gertrudis; Valdés-Urrutia, Lourdes; Galán, Lídice; Valdés-Sosa, Pedro

    2010-05-01

    Recently, a related morphometry-based connection concept has been introduced using local mean cortical thickness and volume to study the underlying complex architecture of the brain networks. In this article, the surface area is employed as a morphometric descriptor to study the concurrent changes between brain structures and to build binarized connectivity graphs. The statistical similarity in surface area between pair of regions was measured by computing the partial correlation coefficient across 186 normal subjects of the Cuban Human Brain Mapping Project. We demonstrated that connectivity matrices obtained follow a small-world behavior for two different parcellations of the brain gray matter. The properties of the connectivity matrices were compared to the matrices obtained using the mean cortical thickness for the same cortical parcellations. The topology of the cortical thickness and surface area networks were statistically different, demonstrating that both capture distinct properties of the interaction or different aspects of the same interaction (mechanical, anatomical, chemical, etc.) between brain structures. This finding could be explained by the fact that each descriptor is driven by distinct cellular mechanisms as result of a distinct genetic origin. To our knowledge, this is the first time that surface area is used to study the morphological connectivity of brain networks. PMID:20083210

  17. 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. PMID:24967698

  18. Microstructural Abnormalities in Language and Limbic Pathways in Orphanage-reared Children: A Diffusion Tensor Imaging Study

    PubMed Central

    Kumar, Ajay; Behen, Michael E.; Singsoonsud, Piti; Veenstra, Amy L.; Wolfe-Christensen, Cortney; Helder, Emily; Chugani, Harry T.

    2013-01-01

    This study utilized diffusion tensor imaging fiber tractography to examine the miscrostructural integrity of limbic and paralimbic white matter tracts in thirty-six children (Mean age=124 months) with histories of early deprivation, raised from birth in orphanages and subsequently adopted into the United States, compared to 16 age-matched typically developing children. We found increased mean diffusivity bilaterally in the arcuate fasciculus, and increased mean diffusivity and reduced fractional anisotropy bilaterally in the uncinate fasciculus and cingulum in children with early deprivation. Microstructural integrity of the left arcuate fasciculus and right cingulum was related to language and behavioral functioning, respectively. White matter abnormalities were also associated with length of deprivation and time in the adoptive home. Our findings suggest that white matter pathways, connecting limbic and paralimbic brain regions is abnormal in children with histories of early deprivation; with some pathways appearing more susceptible to early deprivation than others. PMID:23358628

  19. Reduced fractional anisotropy in the visual limbic pathway of young adults witnessing domestic violence in childhood.

    PubMed

    Choi, Jeewook; Jeong, Bumseok; Polcari, Ann; Rohan, Michael L; Teicher, Martin H

    2012-01-16

    Witnessing domestic violence (WDV) is a traumatic childhood experience associated with increased risk for depression, posttraumatic stress disorder and reduced IQ scores. Specific affects of WDV on brain development have not been assessed. We sought to ascertain whether WDV was associated with abnormalities in white matter (WM) tract integrity using diffusion tensor imaging (DTI). Twenty subjects who witnessed domestic violence (16F/4M, mean age 22.4 ± 2.48 years) but were not physically or sexually abused were compared to 27 healthy controls (19F/8M, 21.9 ± 1.97 years) without exposure to trauma or Axis I and II disorders. DTI images were acquired with a 3T Siemens Trio scanner. Group differences in fractional anisotropy (FA), covaried by age, gender, parental education, perceived financial sufficiency, IQ and degree of exposure to parental verbal aggression were assessed using tract-based spatial statistics (TBSS), which projects FA values onto an alignment-invariant fiber tract representation. FA values in the inferior longitudinal fasciculus of left lateral occipital lobe were significantly lower (P<0.05 corrected for multiple comparison) in the WDV group. FA values correlated inversely with ratings of depression, anxiety, somatization, 'limbic irritability' and neuropsychological measures of processing speed. Measures of radial but not axial diffusivity were affected suggesting alterations in myelination. Degree of FA reduction was associated with duration of witnessing interparental verbal aggression and with exposure between ages 7 and 13 years. The inferior longitudinal fasciculus connects occipital and temporal cortex and is the main component of the visual-limbic pathway that subserves emotional, learning and memory functions that are modality specific to vision. This finding is consistent with the hypothesis that exposure to childhood maltreatment is associated with alterations in fiber pathways that convey the adverse experience to frontal, temporal

  20. Individualized and Clinically Derived Stimuli Activate Limbic Structures in Depression: An fMRI Study

    PubMed Central

    Kessler, Henrik; Taubner, Svenja; Buchheim, Anna; Münte, Thomas F.; Stasch, Michael; Kächele, Horst; Roth, Gerhard; Heinecke, Armin; Erhard, Peter; Cierpka, Manfred; Wiswede, Daniel

    2011-01-01

    Objectives In the search for neurobiological correlates of depression, a major finding is hyperactivity in limbic-paralimbic regions. However, results so far have been inconsistent, and the stimuli used are often unspecific to depression. This study explored hemodynamic responses of the brain in patients with depression while processing individualized and clinically derived stimuli. Methods Eighteen unmedicated patients with recurrent major depressive disorder and 17 never-depressed control subjects took part in standardized clinical interviews from which individualized formulations of core interpersonal dysfunction were derived. In the patient group such formulations reflected core themes relating to the onset and maintenance of depression. In controls, formulations reflected a major source of distress. This material was thereafter presented to subjects during functional magnetic resonance imaging (fMRI) assessment. Results Increased hemodynamic responses in the anterior cingulate cortex, medial frontal gyrus, fusiform gyrus and occipital lobe were observed in both patients and controls when viewing individualized stimuli. Relative to control subjects, patients with depression showed increased hemodynamic responses in limbic-paralimbic and subcortical regions (e.g. amygdala and basal ganglia) but no signal decrease in prefrontal regions. Conclusions This study provides the first evidence that individualized stimuli derived from standardized clinical interviewing can lead to hemodynamic responses in regions associated with self-referential and emotional processing in both groups and limbic-paralimbic and subcortical structures in individuals with depression. Although the regions with increased responses in patients have been previously reported, this study enhances the ecological value of fMRI findings by applying stimuli that are of personal relevance to each individual's depression. PMID:21283580

  1. Reduced Fractional Anisotropy in the Visual Limbic Pathway of Young Adults Witnessing Domestic Violence in Childhood

    PubMed Central

    Choi, Jeewook; Jeong, Bumseok; Polcari, Ann; Rohan, Michael L.; Teicher, Martin H.

    2011-01-01

    Witnessing domestic violence (WDV) is a traumatic childhood experience associated with increased risk for depression, posttraumatic stress disorder and reduced IQ scores. Specific affects of WDV on brain development have not been assessed. We sought to ascertain whether WDV was associated with abnormalities in white matter (WM) tract integrity using diffusion tensor imaging (DTI). Twenty subjects who witnessed domestic violence (16F/ 4M, mean age 22.4±2.48 yrs) but were not physically or sexually abused were compared to 27 healthy controls (19F/ 8M, 21.9±1.97 yrs) without exposure to trauma or Axis I and II disorders. DTI images were acquired with a 3T Siemens Trio scanner. Group differences in fractional anisotropy (FA), covaried by age, gender, parental education, perceived financial sufficiency, IQ and degree of exposure to parental verbal aggression were assessed using tract-based spatial statistics (TBSS), which projects FA values onto an alignment-invariant fiber tract representation. FA values in the inferior longitudinal fasciculus of left lateral occipital lobe were significantly lower (p<0.05 corrected for multiple comparison) in the WDV group. FA values correlated inversely with ratings of depression, anxiety, somatization, ‘limbic irritability’ and neuropsychological measures of processing speed. Measures of radial but not axial diffusivity were affected suggesting alterations in myelination. Degree of FA reduction was associated with duration of witnessing interparental verbal aggression and with exposure between ages 7 – 13 years. The inferior longitudinal fasciculus connects occipital and temporal cortex and is the main component of the visual–limbic pathway that subserves emotional, learning and memory functions that are modality specific to vision. This finding is consistent with the hypothesis that exposure to childhood maltreatment is associated with alterations in fiber pathways that convey the adverse experience to frontal, temporal

  2. Brain activity for chronic knee osteoarthritis: dissociating evoked pain from spontaneous pain

    PubMed Central

    Parks, Elle L.; Geha, Paul Y.; Baliki, Marwan N.; Katz, Jeffrey; Schnitzer, Thomas J.; Apkarian, A. Vania

    2011-01-01

    Chronic pain is a hallmark of osteoarthritis (OA), yet little is known about its properties and representation in the brain. Here we use fMRI combined with psychophysics to study knee pain in 14 OA patients and 9 healthy controls. Mechanical painful pressure stimuli were applied to the knee in both groups and ratings of evoked pain and related brain activity examined. We observe that psychophysical properties and brain activation patterns of evoked pain are essentially the same between OA patients and healthy subjects, and between worse and better OA knees. In OA patients, stimulus-related brain activity could be distinguished from brain activity associated with spontaneous pain. The former activated brain regions commonly observed for acute painful stimuli in healthy subjects, while the spontaneous pain of OA engaged prefrontal-limbic regions closely corresponding to areas observed for spontaneous pain in other chronic pain conditions, such as chronic back pain and post-herpetic neuralgia. Arthritis-related clinical characteristics of knee OA also mapped to prefrontal-limbic regions. In a subgroup of patients (n = 6) we examined brain activity changes for a 2-week, repeat measure, cyclooxygenase-2 inhibitor (valdecoxib) therapy. Treatment decreased spontaneous pain for the worse knee and clinical characteristics of OA, and increased blood and csf levels of the drug which correlated positively with prefrontal-limbic brain activity. These findings indicate dissociation between mechanically induced and spontaneous OA knee pain, the latter engaging brain regions involved in emotional assessment of the self, and challenge the standard clinical view regarding the nature of OA pain. PMID:21315627

  3. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  4. 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

  5. Neuropeptide FF receptors as novel targets for limbic seizure attenuation.

    PubMed

    Portelli, Jeanelle; Meurs, Alfred; Bihel, Frederic; Hammoud, Hassan; Schmitt, Martine; De Kock, Joery; Utard, Valerie; Humbert, Jean-Paul; Bertin, Isabelle; Buffel, Ine; Coppens, Jessica; Tourwe, Dirk; Maes, Veronique; De Prins, An; Vanhaecke, Tamara; Massie, Ann; Balasubramaniam, Ambikaipakan; Boon, Paul; Bourguignon, Jean-Jacques; Simonin, Frederic; Smolders, Ilse

    2015-08-01

    Neuropeptide Y (NPY) is a well established anticonvulsant and first-in-class antiepileptic neuropeptide. In this study, the controversial role of NPY1 receptors in epilepsy was reassessed by testing two highly selective NPY1 receptor ligands and a mixed NPY1/NPFF receptor antagonist BIBP3226 in a rat model for limbic seizures. While BIBP3226 significantly attenuated the pilocarpine-induced seizures, neither of the highly selective NPY1 receptor ligands altered the seizure severity. Administration of the NPFF1/NPFF2 receptor antagonist RF9 also significantly attenuated limbic seizure activity. To further prove the involvement of NPFF receptors in these seizure-modulating effects, low and high affinity antagonists for the NPFF receptors were tested. We observed that the low affinity ligand failed to exhibit anticonvulsant properties while the two high affinity ligands significantly attenuated the seizures. Continuous NPFF1 receptor agonist administration also inhibited limbic seizures whereas bolus administration of the NPFF1 receptor agonist was without effect. This suggests that continuous agonist perfusion could result in NPFF1 receptor desensitization and mimic NPFF1 receptor antagonist administration. Our data unveil for the first time the involvement of the NPFF system in the management of limbic seizures. PMID:25963417

  6. 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. PMID:25291405

  7. Limbic Networks and Epileptiform Synchronization: The View from the Experimental Side

    PubMed Central

    Behr, Charles; D’Antuono, Margherita; Hamidi, Shabnam; Herrington, Rochelle; Lévesque, Maxime; Salami, Pariya; Shiri, Zahra; Köhling, Rüdiger; Avoli, Massimo

    2016-01-01

    In this review, we summarize findings obtained in acute and chronic epilepsy models and in particular experiments that have revealed how neuronal networks in the limbic system—which is closely involved in the pathophysiogenesis of mesial temporal lobe epilepsy (MTLE)—produce hypersynchronous discharges. MTLE is often associated with a typical pattern of brain damage known as mesial temporal sclerosis, and it is one of the most refractory forms of partial epilepsy in adults. Specifically, we will address the cellular and pharmacological features of abnormal electrographic events that, as in MTLE patients, can occur in in vivo and in vitro animal models; these include interictal and ictal discharges along with high-frequency oscillations. In addition, we will consider how different limbic structures made hyperexcitable by acute pharmacological manipulations interact during epileptiform discharge generation. We will also review the electrographic characteristics of two types of seizure onsets that are most commonly seen in human and experimental MTLE as well as in in vitro models of epileptiform synchronization. Finally, we will address the role played by neurosteroids in reducing epileptiform synchronization and in modulating epileptogenesis. PMID:25078499

  8. 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

  9. Virtual reality adaptive stimulation of limbic networks in the mental readiness training.

    PubMed

    Cosić, Kresimir; Popović, Sinisa; Kostović, Ivica; Judas, Milos

    2010-01-01

    A significant proportion of severe psychological problems in recent large-scale peacekeeping operations underscores the importance of effective methods for strengthening the stress resilience. Virtual reality (VR) adaptive stimulation, based on the estimation of the participant's emotional state from physiological signals, may enhance the mental readiness training (MRT). Understanding neurobiological mechanisms by which the MRT based on VR adaptive stimulation can affect the resilience to stress is important for practical application in the stress resilience management. After the delivery of a traumatic audio-visual stimulus in the VR, the cascade of events occurs in the brain, which evokes various physiological manifestations. In addition to the "limbic" emotional and visceral brain circuitry, other large-scale sensory, cognitive, and memory brain networks participate with less known impact in this physiological response. The MRT based on VR adaptive stimulation may strengthen the stress resilience through targeted brain-body interactions. Integrated interdisciplinary efforts, which would integrate the brain imaging and the proposed approach, may contribute to clarifying the neurobiological foundation of the resilience to stress. PMID:20543262

  10. 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. PMID:20946958

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

    PubMed

    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

  12. 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

  13. [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. PMID:23789489

  14. Regional contraction of brain surface area involves three large-scale networks in schizophrenia.

    PubMed

    Palaniyappan, Lena; Mallikarjun, Pavan; Joseph, Verghese; White, Thomas P; Liddle, Peter F

    2011-07-01

    In schizophrenia, morphological changes in the cerebral cortex have been primarily investigated using volumetric or cortical thickness measurements. In healthy subjects, as the brain size increases, the surface area expands disproportionately when compared to the scaling of cortical thickness. In this structural MRI study, we investigated the changes in brain surface area in schizophrenia by constructing relative areal contraction/expansion maps showing group differences in surface area using Freesurfer software in 57 patients and 41 controls. We observed relative areal contraction affecting Default Mode Network, Central Executive Network and Salience Network, in addition to other regions in schizophrenia. We confirmed the surface area reduction across these three large-scale brain networks by undertaking further region-of-interest analysis of surface area. We also observed a significant hemispheric asymmetry in the surface area changes, with the left hemisphere showing a greater reduction in the areal contraction maps. Our findings suggest that a fundamental disturbance in cortical expansion is likely in individuals who develop schizophrenia. PMID:21497489

  15. [A case of smoldering anti-leucine-rich glioma-inactivated 1 (LGI1) antibody-associated limbic encephalitis with faciobrachial dystonic seizure].

    PubMed

    Nakaoku, Yuriko; Maki, Takakuni; Kanazawa, Kyoko; Matsumoto, Riki; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2013-01-01

    We report a 59-year-old right-handed woman with smoldering leucine-rich glioma-inactivated 1 (LGI1) antibody-associated limbic encephalitis (LE) following faciobrachial dystonic seizures. During 8 months before her admission, she developed partial seizures manifesting very brief and very frequent dystonia in her right hand sometimes with oral automatism and loss of awareness. In addition, she showed psychiatric disturbances such as emotionally labile condition and personality changes. On admission, neuropsychological examination revealed short-term memory impairment. During electroencephalography (EEG) monitoring, ictal EEG showed rhythmic delta waves and interictal EEG showed intermittent irregular slow waves at the bilateral frontotemporal area. Brain MRI demonstrated high T2/FLAIR signal changes in the left amygdala expanding into the left hippocampus. FDG-PET showed hypermetabolism in the left amygdala, hippocampus and the bilateral basal ganglia. Cerebrospinal fluid analysis was unremarkable. There were no signs of malignant tumor detected on systemic examination. LGI1 antibody was positive in the serum and the cerebrospinal fluid and the clinical diagnosis of LGI1 antibody-associated LE was confirmed. Her symptoms and the abnormalities in the brain MRI/FDG-PET showed immediate improvement after anti-epileptic and steroid therapy. PMID:24097318

  16. Optimizing limbic selective D2/D3 receptor occupancy by risperidone: a [123I]-epidepride SPET study.

    PubMed

    Bressan, Rodrigo A; Erlandsson, Kjell; Jones, Hugh M; Mulligan, Rachel S; Ell, Peter J; Pilowsky, Lyn S

    2003-02-01

    Selective action at limbic cortical dopamine D2-like receptors is a putative mechanism of atypical antipsychotic efficacy with few extrapyramidal side effects. Although risperidone is an atypical antipsychotic with high affinity for D2 receptors, low-dose risperidone treatment is effective without inducing extrapyramidal symptoms. The objective was to test the hypothesis that treatment with low-dose risperidone results in 'limbic selective' D2/D3 receptor blockade in vivo. Dynamic single photon emission tomography (SPET) sequences were obtained over 5 hours after injection of [123I]-epidepride (approximately 150 MBq), using a high-resolution triple-headed brain scanner (Marconi Prism 3000XP). Kinetic modelling was performed using the simplified reference region model to obtain binding potential values. Estimates of receptor occupancy were made relative to a normal volunteer control group (n = 5). Six patients treated with low-dose risperidone (mean = 2.6 mg) showed moderate levels of D2/D3 occupancy in striatum (49.9%), but higher levels of D2/D3 occupancy in thalamus (70.8%) and temporal cortex (75.2%). Occupancy values in striatum were significantly different from thalamus (F (1,4) = 26.3, p < 0.01) and from temporal cortex (F (1,4) = 53.4, p < 0.01). This is the first study to evaluate striatal and extrastriatal occupancy of risperidone. Low dose treatment with risperidone achieves a similar selectivity of limbic cortical over striatal D2/D3 receptor blockade to that of atypical antipsychotics with lower D2/D3 affinity such as clozapine, olanzapine and quetiapine. This finding is consistent with the relevance of 'limbic selective' D2/D3 receptor occupancy to the therapeutic efficacy of atypical antipsychotic drugs. PMID:12544369

  17. 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

  18. 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. PMID:15050586

  19. 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

  20. Distribution of androgen receptor in microdissected brain areas of the female baboon (Papio cynocephalus).

    PubMed

    Handa, R J; Roselli, C E; Resko, J A

    1988-03-29

    We measured androgen receptors in the brain and pituitary of 4 female baboons (Papio cynocephalus) by the in vitro binding of methyltrienolone (R1881) to cytosols from 17 brain subregions as well as anterior and posterior pituitaries. High levels of AR were detected in anterior (22.1 +/- 7.1 (S.E.M.) fmol/mg protein) and posterior pituitary (12.6 +/- 3.3 fmol/mg protein). In brain tissue, the highest androgen receptor levels were found in the infundibular nucleus/median eminence (9.4 +/- 2.3 fmol/mg protein), ventromedial nucleus (6.3 +/- 1.7 fmol/mg protein) and periventricular area (4.9 +/- 1.3 fmol/mg protein). Saturation analysis of anterior pituitary and brain tissue (pool of hypothalamic, preoptic area, amygdala and septum remaining after microdissection of brain nuclei) showed that [3H]R1881 binds to the androgen receptor with high specificity and affinity (Kd = 1.25 x 10(-10) M, 0.45 x 10(-10) M, in anterior pituitary and HPA cytosol, respectively). Serum testosterone levels were low in all animals (0.59 +/- 0.26 ng/ml). With these data we described the quantitative distribution of androgen receptor in the pituitary and in specific brain nuclei in a species of nonhuman primate. The distribution is similar in many respects to that described in the male rat and the data suggest a conservation of androgen receptor distribution across species. PMID:3259151

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

    PubMed

    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

  2. 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

  3. Mephedrone alters basal ganglia and limbic dynorphin systems

    PubMed Central

    German, Christopher L.; Alburges, Mario E.; Hoonakker, Amanda J.; Fleckenstein, Annette E.; Hanson, Glen R.

    2014-01-01

    Mephedrone (4-methymethcathinone) is a synthetic cathinone designer drug that disrupts central nervous system (CNS) dopamine (DA) signaling. Numerous central neuropeptide systems reciprocally interact with dopaminergic neurons to provide regulatory counterbalance, and are altered by aberrant DA activity associated with stimulant exposure. Endogenous opioid neuropeptides are highly concentrated within dopaminergic CNS regions and facilitate many rewarding and aversive properties associated with drug use. Dynorphin, an opioid neuropeptide and kappa receptor agonist, causes dysphoria and aversion to drug consumption through signaling within the basal ganglia and limbic systems, which is affected by stimulants. This study evaluated how mephedrone alters basal ganglia and limbic system dynorphin content, and the role of DA signaling in these changes. Repeated mephedrone administrations (4 × 25 mg/kg/injection, 2-h intervals) selectively increased dynorphin content throughout the dorsal striatum and globus pallidus, decreased dynorphin content within the frontal cortex, and did not alter dynorphin content within most limbic system structures. Pre-treatment with D1-like (SCH-23380) or D2-like (eticlopride) antagonists blocked mephedrone-induced changes in dynorphin content in most regions examined, indicating altered dynorphin activity is a consequence of excessive DA signaling. PMID:25155699

  4. Mephedrone alters basal ganglia and limbic neurotensin systems

    PubMed Central

    German, Christopher L.; Hoonakker, Amanda H.; Fleckenstein, Annette E.; Hanson, Glen R.

    2014-01-01

    Mephedrone (4-methylmethcathinone) is a synthetic cathinone designer drug that alters presynaptic dopamine (DA) activity like many psychostimulants. However, little is known about the postsynaptic dopaminergic impacts of mephedrone. The neuropeptide neurotensin (NT) provides inhibitory feedback for basal ganglia and limbic DA pathways, and postsynaptic D1-like and D2-like receptor activity affects NT tissue levels. This study evaluated how mephedrone alters basal ganglia and limbic system NT content and the role of NT receptor activation in drug consumption behavior. Four 25 mg/kg injections of mephedrone increased NT content in basal ganglia (striatum, substantia nigra and globus pallidus) and the limbic regions (nucleus accumbens core), while a lower dosage (5 mg/kg/injection) only increased striatal NT content. Mephedrone-induced increases in basal ganglia NT levels were mediated by D1-like receptors in the striatum and the substantia nigra by both D1-like and D2-like receptors in the globus pallidus. Mephedrone increased substance P content, another neuropeptide, in the globus pallidus, but not in the dorsal striatum or substantia nigra. Finally, the NT receptor agonist PD149163 blocked mephedrone self-administration, suggesting reduced NT release, as indicated by increased tissue levels, likely contributing to patterns of mephedrone consumption. PMID:24678634

  5. 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. PMID:26190301

  6. [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. PMID:857280

  7. 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. PMID:24349687

  8. 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

  9. 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

  10. 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. PMID:18752396

  11. Brain development during adolescence: A mixed-longitudinal investigation of cortical thickness, surface area, and volume.

    PubMed

    Vijayakumar, Nandita; Allen, Nicholas B; Youssef, George; Dennison, Meg; Yücel, Murat; Simmons, Julian G; Whittle, Sarah

    2016-06-01

    What we know about cortical development during adolescence largely stems from analyses of cross-sectional or cohort-sequential samples, with few studies investigating brain development using a longitudinal design. Further, cortical volume is a product of two evolutionarily and genetically distinct features of the cortex - thickness and surface area, and few studies have investigated development of these three characteristics within the same sample. The current study examined maturation of cortical thickness, surface area and volume during adolescence, as well as sex differences in development, using a mixed longitudinal design. 192 MRI scans were obtained from 90 healthy (i.e., free from lifetime psychopathology) adolescents (11-20 years) at three time points (with different MRI scanners used at time 1 compared to 2 and 3). Developmental trajectories were estimated using linear mixed models. Non-linear increases were present across most of the cortex for surface area. In comparison, thickness and volume were both characterised by a combination of non-linear decreasing and increasing trajectories. While sex differences in volume and surface area were observed across time, no differences in thickness were identified. Furthermore, few regions exhibited sex differences in the cortical development. Our findings clearly illustrate that volume is a product of surface area and thickness, with each exhibiting differential patterns of development during adolescence, particularly in regions known to contribute to the development of social-cognition and behavioral regulation. These findings suggest that thickness and surface area may be driven by different underlying mechanisms, with each measure potentially providing independent information about brain development. Hum Brain Mapp 37:2027-2038, 2016. © 2016 Wiley Periodicals, Inc. PMID:26946457

  12. 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

  13. 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

  14. 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…

  15. 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. PMID:24727703

  16. Development of large-scale functional brain networks in children.

    PubMed

    Supekar, Kaustubh; Musen, Mark; Menon, Vinod

    2009-07-01

    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

  17. 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.

  18. Multiple interacting brain areas underlie successful spatiotemporal memory retrieval in humans.

    PubMed

    Schedlbauer, Amber M; Copara, Milagros S; Watrous, Andrew J; Ekstrom, Arne D

    2014-01-01

    Emerging evidence suggests that our memories for recent events depend on a dynamic interplay between multiple cortical brain regions, although previous research has also emphasized a primary role for the hippocampus in episodic memory. One challenge in determining the relative importance of interactions between multiple brain regions versus a specific brain region is a lack of analytic approaches to address this issue. Participants underwent neuroimaging while retrieving the spatial and temporal details of a recently experienced virtual reality environment; we then employed graph theory to analyze functional connectivity patterns across multiple lobes. Dense, large-scale increases in connectivity during successful memory retrieval typified network topology, with individual participant performance correlating positively with overall network density. Within this dense network, the hippocampus, prefrontal cortex, precuneus, and visual cortex served as "hubs" of high connectivity. Spatial and temporal retrieval were characterized by distinct but overlapping "subnetworks" with higher connectivity within posterior and anterior brain areas, respectively. Together, these findings provide new insight into the neural basis of episodic memory, suggesting that the interactions of multiple hubs characterize successful memory retrieval. Furthermore, distinct subnetworks represent components of spatial versus temporal retrieval, with the hippocampus acting as a hub integrating information between these two subnetworks. PMID:25234342

  19. 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

  20. 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. PMID:25540983

  1. Melanocortin 4 Receptor and Dopamine D2 Receptor Expression in Brain Areas Involved in Food Intake

    PubMed Central

    Yoon, Ye Ran

    2015-01-01

    Background The melanocortin 4 receptor (MC4R) is involved in the regulation of homeostatic energy balance by the hypothalamus. Recent reports showed that MC4R can also control the motivation for food in association with a brain reward system, such as dopamine. We investigated the expression levels of MC4R and the dopamine D2 receptor (D2R), which is known to be related to food rewards, in both the hypothalamus and brain regions involved in food rewards. Methods We examined the expression levels of D2R and MC4R by dual immunofluorescence histochemistry in hypothalamic regions and in the bed nucleus of the stria terminalis (BNST), the central amygdala, and the ventral tegmental area of transgenic mice expressing enhanced green fluorescent protein under the control of the D2R gene. Results In the hypothalamic area, significant coexpression of MC4R and D2R was observed in the arcuate nucleus. We observed a significant coexpression of D2R and MC4R in the BNST, which has been suggested to be an important site for food reward. Conclusion We suggest that MC4R and D2R function in the hypothalamus for control of energy homeostasis and that within the brain regions related with rewards, such as the BNST, the melanocortin system works synergistically with dopamine for the integration of food motivation in the control of feeding behaviors. PMID:26790386

  2. 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. PMID:25813749

  3. [Localization of human brain areas activated for chaotic and ordered pattern perception].

    PubMed

    Fokin, V A; Shelepin, Iu E; Kharauzov, A K; Trufanov, G E; Sevost'ianov, A V; Pronin, S V; Koskin, S A

    2007-10-01

    The aim of our work was to localize cortical areas involved in the processing of incomplete figures using functional MRI (fMRI) for 8 healthy volunteers (18-30 year old) with the did of anatomical and fMRI fast imaging technique: echo planar imaging (EPI), whole brain scan (36 slices) matrix 64 x 64, 3.7 second. We used 1.5 T MR-scanner and BOLD-method (Blood Oxygenation Level Dependent), based on distinctions of magnetic properties of hemoglobin. Fast imaging technique on modern MR-scanners with > or = 1.5 T provides precise statistical maps of oxygenation increase with high spatial resolution. For test stimuli we used matrix of Gabor grating. We used two types of 10 x 10 matrices with chaotic and ordered orientation of Gabor gratings. The size, brightness and contrast of the stimuli were identical. The chaotic and ordered patterns activated different brain areas. We establish that ordered patterns activated only primary visual cortex - V1 and V2, (BA17-18), wheareas chaotic patterns activated in addition primary visual cortex, the V3,V4,V5 (BA19) of the occipital cortex and the area 7 of parietal area (BA7) classification. Decision making for that task is localized in prefrontal and frontal cortex, including (BA 6, 9, 10). PMID:18074783

  4. Neural mechanisms of auditory categorization: from across brain areas to within local microcircuits

    PubMed Central

    Tsunada, Joji; Cohen, Yale E.

    2014-01-01

    Categorization enables listeners to efficiently encode and respond to auditory stimuli. Behavioral evidence for auditory categorization has been well documented across a broad range of human and non-human animal species. Moreover, neural correlates of auditory categorization have been documented in a variety of different brain regions in the ventral auditory pathway, which is thought to underlie auditory-object processing and auditory perception. Here, we review and discuss how neural representations of auditory categories are transformed across different scales of neural organization in the ventral auditory pathway: from across different brain areas to within local microcircuits. We propose different neural transformations across different scales of neural organization in auditory categorization. Along the ascending auditory system in the ventral pathway, there is a progression in the encoding of categories from simple acoustic categories to categories for abstract information. On the other hand, in local microcircuits, different classes of neurons differentially compute categorical information. PMID:24987324

  5. Acute nonparaneoplastic limbic encephalitis in childhood: a case series in Japan.

    PubMed

    Sakuma, Hiroshi; Sugai, Kenji; Sasaki, Masayuki

    2010-09-01

    Limbic encephalitis not associated with malignancy was investigated in Japanese children, with particular focus on clinical features distinct from adult cases. Clinical, laboratory, and radiographic findings were studied in pediatric nonparaneoplastic limbic encephalitis, based on a literature review and questionnaire-based analyses. Analysis of 14 cases revealed the predominance of seizure occurrence, disturbance in consciousness, and frequent extralimbic signs. The majority manifested antecedent febrile illnesses, suggesting the involvement of infection-induced autoimmunity targeted to neuronal antigens. These clinical observations indicate a child-specific phenotype of limbic encephalitis. Further studies on its immunopathogenesis are needed to determine whether childhood limbic encephalitis is a distinct subcategory. PMID:20691937

  6. 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…

  7. 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. PMID

  8. 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. PMID:26412254

  9. 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. PMID:27375466

  10. 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

  11. Lithium lengthens circadian period of cultured brain slices in area specific manner.

    PubMed

    Yoshikawa, Tomoko; Honma, Sato

    2016-11-01

    Lithium has been used for the treatment of bipolar disorder (BD). However, the mechanisms how lithium exerts its mood stabilizing effects remain to be studied. The disorder in circadian pacemaking has been suggested as an underlying mechanism of the characteristic mood instability of the BD. Lithium is also known to lengthen the circadian periods. We recently proposed that chronic methamphetamine treatment induced circadian oscillation as a complex oscillator including multiple dopaminergic brain areas, and the complex oscillator regulates behavior rhythm independent from the central circadian oscillator in the suprachiasmatic nucleus (SCN). Sleep-wake pattern of rapid cycling BD exhibits similar rhythm disorganization to methamphetamine treated animals. Therefore, we hypothesized that the dysregulated circadian rhythm in BD patients is caused by desynchronization of sleep-wake rhythms from the central clock in the SCN, and that mood stabilizing effect of lithium is achieved through their resynchronization. In the present experiment, we examined how lithium affects the circadian rhythms of brain areas involved in the complex oscillator as well as the SCN. Here we report that lithium lengthens the circadian periods in the SCN, olfactory bulb, median eminence and substantia nigra with dose and area specific manner. The effective lithium dose was much higher than the plasma levels that are required for lengthening the circadian behavior rhythms as well for therapeutic use. Low dose of lithium did not lengthen the period but enhanced the amplitude of circadian rhythms, which may exert therapeutic effects on BD. PMID:27478137

  12. Variability of magnetoencephalographic sensor sensitivity measures as a function of age, brain volume and cortical area

    PubMed Central

    Irimia, Andrei; Erhart, Matthew J.; Brown, Timothy T.

    2014-01-01

    Objective To assess the feasibility and appropriateness of magnetoencephalography (MEG) for both adult and pediatric studies, as well as for the developmental comparison of these factors across a wide range of ages. Methods For 45 subjects with ages from 1 to 24 years (infants, toddlers, school-age children and young adults), lead fields (LFs) of MEG sensors are computed using anatomically realistic boundary element models (BEMs) and individually-reconstructed cortical surfaces. Novel metrics are introduced to quantify MEG sensor focality. Results The variability of MEG focality is graphed as a function of brain volume and cortical area. Statistically significant differences in total cerebral volume, cortical area, MEG global sensitivity and LF focality are found between age groups. Conclusions Because MEG focality and sensitivity differ substantially across the age groups studied, the cortical LF maps explored here can provide important insights for the examination and interpretation of MEG signals from early childhood to young adulthood. Significance This is the first study to (1) investigate the relationship between MEG cortical LFs and brain volume as well as cortical area across development, and (2) compare LFs between subjects with different head sizes using detailed cortical reconstructions. PMID:24589347

  13. 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. PMID:26537783

  14. 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.

  15. 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…

  16. 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. PMID:23073928

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

    PubMed Central

    Stone, Valerie E.; Cosmides, Leda; Tooby, John; Kroll, Neal; Knight, Robert T.

    2002-01-01

    Social exchange is a pervasive feature of human social life. Models in evolutionary biology predict that for social exchange to evolve in a species, individuals must be able to detect cheaters (nonreciprocators). Previous research suggests that humans have a cognitive mechanism specialized for detecting cheaters. Here we provide neurological evidence indicating that social exchange reasoning can be selectively impaired while reasoning about other domains is left intact. The patient, R.M., had extensive bilateral limbic system damage, affecting orbitofrontal cortex, temporal pole, and amygdala. We compared his performance on two types of reasoning problem that were closely matched in form and equally difficult for control subjects: social contract rules (of the form, “If you take the benefit, then you must satisfy the requirement”) and precaution rules (of the form, “If you engage in hazardous activity X, then you must take precaution Y”). R.M. performed significantly worse in social contract reasoning than in precaution reasoning, when compared both with normal controls and with other brain-damaged subjects. This dissociation in reasoning performance provides evidence that reasoning about social exchange is a specialized and separable component of human social intelligence, and is consistent with other research indicating that the brain processes information about the social world differently from other types of information. PMID:12177408

  18. A locus on mouse Ch10 influences susceptibility to limbic seizure severity: fine mapping and in silico candidate gene analysis

    PubMed Central

    Winawer, Melodie R.; Klassen, Tara L.; Teed, Sarah; Shipman, Marissa; Leung, Emily H.; Palmer, Abraham A.

    2014-01-01

    Identification of genes contributing to mouse seizure susceptibility can reveal novel genes or pathways that provide insight into human epilepsy. Using mouse chromosome substitution strains and interval-specific congenic strains (ISCS), we previously identified an interval conferring pilocarpine-induced limbic seizure susceptibility on distal mouse Chromosome 10 (Ch10). We narrowed the region by generating subcongenics with smaller A/J Ch10 segments on a C57BL/6J (B6) background and tested them with pilocarpine. We also tested pilocarpine susceptible congenics for 6Hz ECT, another model of limbic seizure susceptibility, to determine whether the susceptibility locus might have a broad effect on neuronal hyperexcitability across more than one mode of limbic seizure induction. ISCS Line 1, which contained the distal 2.7 Mb segment from A/J (starting at rs29382217), was more susceptible to both pilocarpine and ECT. Line 2, which was a subcongenic of Line1 (starting at rs13480828), was not susceptible; thus defining a 1.0 Mb critical region that was unique to Line1. Bioinformatic approaches identified 52 human orthologues within the unique Line 1 susceptibility region, the majority syntenic to human Ch12. Applying an epilepsy network analysis of known and suspected excitability genes and examination of interstrain genomic and brain expression differences revealed novel candidates within the region. These include Stat2, which plays a role in hippocampal GABA receptor expression after status epilepticus, and novel candidates Pan2, Cdk2, Gls2, and Cs, which are involved in neural cell differentiation, cellular remodeling, and embryonic development. Our strategy may facilitate discovery of novel human epilepsy genes. PMID:24373497

  19. 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. PMID:25387340

  20. Leptin Therapy Alters Appetite and Neural Responses to Food Stimuli in Brain Areas of Leptin-Sensitive Subjects Without Altering Brain Structure

    PubMed Central

    Farr, Olivia M.; Fiorenza, Christina; Papageorgiou, Panagiotis; Brinkoetter, Mary; Ziemke, Florencia; Koo, Bang-Bon; Rojas, Rafael

    2014-01-01

    Context: Leptin is a key regulator of energy intake and expenditure. Individuals with congenital leptin deficiency demonstrate structural and functional brain changes when given leptin. However, whether acquired leptin deficiency may operate similarly is unclear. Objective: We set out to determine whether the brains of individuals with acquired leptin deficiency may react to leptin in a similar manner. Design: We used functional magnetic resonance imaging before and after short- and long-term metreleptin treatment in three leptin-sensitive patients with acquired hypoleptinemia. Nine healthy women were scanned as normoleptinemic controls. Setting: The setting was an academic medical center. Patients or Other Participants: The participants were 3 hypoleptinemic women and nine normoleptinemic, matched women. Interventions: We used metreleptin, recombinant leptin, therapy for 24 weeks in hypoleptinemic women only. Main Outcome Measure: We measured neural changes in response to viewing food as compared to nonfood images. We hypothesized that metreleptin treatment would increase brain activity in areas related to cognitive control and inhibition and would decrease brain activity in areas related to reward processing, as compared to the normoleptinemic counterparts. Results: Unlike patients with congenital leptin deficiency, hypoleptinemic patients demonstrated no structural brain differences from healthy controls and/or structural changes in response to treatment. Short-term metreleptin treatment in leptin-sensitive hypoleptinemic subjects enhances areas involved in detecting the salience and rewarding value of food during fasting, whereas long-term treatment decreases attention to food and the rewarding value of food after feeding. Furthermore, hypothalamic activity is modulated by metreleptin treatment, and leptin decreases functional connectivity of the hypothalamus to key feeding-related areas in these hypoleptinemic subjects. Conclusions: Leptin replacement in

  1. 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

  2. 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

  3. [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. PMID:26876086

  4. 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. PMID:25300959

  5. A voxel-based lesion study on facial emotion recognition after penetrating brain injury.

    PubMed

    Dal Monte, Olga; Krueger, Frank; Solomon, Jeffrey M; Schintu, Selene; Knutson, Kristine M; Strenziok, Maren; Pardini, Matteo; Leopold, Anne; Raymont, Vanessa; Grafman, Jordan

    2013-08-01

    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

  6. Neuronal Heterotopias Affect the Activities of Distant Brain Areas and Lead to Behavioral Deficits.

    PubMed

    Ishii, Kazuhiro; Kubo, Ken-ichiro; Endo, Toshihiro; Yoshida, Keitaro; Benner, Seico; Ito, Yukiko; Aizawa, Hidenori; Aramaki, Michihiko; Yamanaka, Akihiro; Tanaka, Kohichi; Takata, Norio; Tanaka, Kenji F; Mimura, Masaru; Tohyama, Chiharu; Kakeyama, Masaki; Nakajima, Kazunori

    2015-09-01

    Neuronal heterotopia refers to brain malformations resulting from deficits of neuronal migration. Individuals with heterotopias show a high incidence of neurological deficits, such as epilepsy. More recently, it has come to be recognized that focal heterotopias may also show a range of psychiatric problems, including cognitive and behavioral impairments. However, because focal heterotopias are not always located in the brain areas responsible for the symptoms, the causal relationship between the symptoms and heterotopias remains elusive. In this study, we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited spatial working memory deficit and low competitive dominance behavior, which have been shown to be closely associated with the activity of the medial prefrontal cortex (mPFC) in rodents. Analysis of the mPFC activity revealed that the immediate-early gene expression was decreased and the local field potentials of the mPFC were altered in the mice with heterotopias compared with the control mice. Moreover, activation of these ectopic and overlying sister neurons using the DREADD (designer receptor exclusively activated by designer drug) system improved the working memory deficits. These findings suggest that cortical regions containing focal heterotopias can affect distant brain regions and give rise to behavioral abnormalities. Significance statement: Recent studies reported that patients with heterotopias have a variety of clinical symptoms, such as cognitive disturbance, psychiatric symptoms, and autistic behavior. However, the causal relationship between the symptoms and heterotopias remains elusive. Here we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited behavioral deficits that have been shown to be associated with the mPFC activity in rodents. The existence of heterotopias indeed altered the neural activities of the mPFC, and

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

    PubMed

    Joseph, R

    1982-01-01

    Discussed evidence and assumptions that concern hemispheric laterality and asymmetrical functional representation. It is hypothesized that the asymmetrical linguistic-motor vs. sensory-spatial-affective representation of function may be a result of differential rates of cortical, subcortical and spinal motor-sensory maturation. Evidence with regard to embryological and early postnatal neurological development is reviewed. It is argued that motor areas mature before sensory and that the left hemisphere develops prior to the right, such that the left hemisphere gains a competitive advantage in the acquisition of motor representation, whereas the later maturing right has an advantage in the establishment of sensory-affective synaptic representation, including that of limbic mediation. The influences of these differing maturational events on cognitive and psychic functioning are examined, particularly with regard to limbic influences on the development of language, thought, and mental imagery, and the effects of early emotional experience on later behavior. Thinking is viewed in part as a left hemisphere internalization of egocentric language, the internalization of which corresponds to the increasing maturation of intra-cortical and subcortical structures and fiber pathways, and the myelination of the callosal connections that subserve information transfer between the hemispheres. It is argued that thought is a means of organizing, interpreting, and explaining impulses that arise in the non-linguistic portions of the nervous system so that the language dependent regions may achieve understanding. In addition, the neurodynamics and mechanisms involved in the mislabeling, misinterpretation, and inhibition of impulses, desires, and emotional expression are discussed in relation to disturbances in psychic functioning. PMID:7056873

  8. The limbic circuitry underlying cocaine seeking encompasses the PPTg/LDT

    PubMed Central

    Schmidt, Heath D.; Famous, Katie R.; Pierce, R. Christopher

    2009-01-01

    The direct glutamatergic projection from the medial prefrontal cortex (mPFC) to the nucleus accumbens plays a critical role in mediating the reinstatement of cocaine-seeking behavior. The mPFC also sends glutamatergic projections to the pedunculopontine tegmental nucleus (PPTg)/laterodorsal tegmental nucleus (LDT), which in turn sends glutamatergic and cholinergic efferents to the ventral tegmental area (VTA) where they synapse on dopaminergic cells that innervate limbic structures including the nucleus accumbens. The goal of these experiments was to examine a potential role for the PPTg/LDT in the reinstatement of cocaine seeking. All rats were trained to self-administer cocaine (0.25 mg, i.v.) on a fixed-ratio 5 (FR5) schedule of reinforcement. Cocaine self-administration behavior was extinguished and a series of subsequent pharmacological experiments were performed to assess the potential role of the mPFC, PPTg/LDT and VTA in the reinstatement of cocaine seeking. Administration of the D1-like dopamine receptor agonist SKF-81297 (1.0 μg) directly into the mPFC produced a small, but statistically significant, increase in cocaine-seeking behavior. Furthermore, microinjection of the ionotropic glutamate receptor antagonist CNQX (0.3 μg) into the PPTg/LDT attenuated the reinstatement of drug seeking induced by a priming injection of cocaine (10 mg/kg, i.p.). Intra-VTA administration of CNQX, the nicotinic receptor antagonist mecamylamine (10.0 μg) or the muscarinic receptor antagonist scopolamine (24.0 μg) also blocked cocaine seeking. Taken together, these results suggest that cocaine priming-induced reinstatement of drug seeking is mediated in part by a serial polysynaptic limbic subcircuit encompassing the mPFC, PPTg/LDT and VTA. PMID:19788581

  9. Evaluation of large-sized brains for neurotoxic endpoints.

    PubMed

    Garman, Robert H

    2003-01-01

    Sampling of large-sized brains (eg, dog, primate) for microscopic examination is frequently inadequate to detect localized neurotoxic injury. Furthermore, the examination of H&E-stained sections alone will often be insufficient for the detection of subtle neuropathogic alteration. It is imperative for any pathologist evaluating brain sections to have knowledge of microscopic neuroanatomy and to also have some understanding of basic neurochemistry. When a focus of degeneration is detected within the brain, the pathologist needs to ascertain not only the specific anatomic location of this focus but also the neuroanatomic regions that project to and receive output from the injured focus. Because of the complexity of brain circuitry and the fact that the brain contains many distinctive neuron populations, many more brain sections are required for adequate microscopic evaluation than for any other body organ. Deciding which and how many areas should be examined, microscopically, from a large size brain is often problematic. Although any sampling protocol will be influenced by what is known about the test chemical, it has been well established that certain regions of the brain (eg, hippocampus and other components of the limbic system, basal ganglia, Purkinje neurons) are more susceptible than others to a variety of physical, metabolic, and chemical insults. Knowledge of these regional sensitivities will assist in guiding the pathologist in the development of an adequate sampling protocol. PMID:12597429

  10. [A Patient with Acute Limbic Encephalitis Associated with Anti-Glutamate Receptor Antibodies and Subsequent Optic Neuritis].

    PubMed

    Murakami, Aya; Nakamura, Masataka; Kaneko, Satoshi; Takahashi, Yukitoshi; Kusaka, Hirofumi

    2016-03-01

    A 19-year-old woman presented with headache and fever. Cerebrospinal fluid (CSF) analysis revealed increased pressure (>200 mmH2O) and pleocytosis. Brain MRI showed high intensity in the medial part of the right temporal lobe, insular regions, and basal ganglia of the right hemisphere on fluid attenuated inversion recovery images. Based on a tentative diagnosis of limbic encephalitis caused by viral infection, acyclovir therapy was started. However, 10 days after admission, a right superior temporal quadrantanopia developed in the left eye. MRI detected abnormal intensity in the left optic nerve on short tau inversion recovery images. After three courses of steroid pulse therapy, the optic neuritis quickly improved and the patient was maintained on subsequent oral administration of prednisolone, without relapse for one year. The CSF was positive for anti-glutamate receptor (GluR) antibodies (GluN2B, GluN1, and GluD2); however, anti-N-methyl-D-aspartate receptor antibody was not detected in both serum and CSF with cell-based asseys. Compared to previously reported anti-GluR positive cases combined with optic neuritis, the clinical outcome of our patient was short, with good prognosis. Our results indicate that an autoimmune mechanism involving anti-GluR antibodies contributes to the pathogenesis of optic neuritis as well as limbic encephalitis. PMID:27001777

  11. Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology.

    PubMed

    Hultman, Rainbo; Mague, Stephen D; Li, Qiang; Katz, Brittany M; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D; Dzirasa, Kafui

    2016-07-20

    Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1 Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. PMID:27346529

  12. Cognitive Impairments Preceding and Outlasting Autoimmune Limbic Encephalitis

    PubMed Central

    Gross, Robert; Davis, Jennifer; Roth, Julie; Querfurth, Henry

    2016-01-01

    Mild cognitive impairment (MCI) can be the initial manifestation of autoimmune limbic encephalitis (ALE), a disorder that at times presents a diagnostic challenge. In addition to memory impairment, clinical features that might suggest this disorder include personality changes, agitation, insomnia, alterations of consciousness, and seizures. Once recognized, ALE typically responds to treatment with immune therapies, but long-term cognitive deficits may remain. We report two cases of patients with MCI who were ultimately diagnosed with ALE with antibodies against the voltage gated potassium channel complex. Months after apparent resolution of their encephalitides, both underwent neuropsychological testing, which demonstrated persistent cognitive deficits, primarily in the domains of memory and executive function, for cases 1 and 2, respectively. A brief review of the literature is included. PMID:26881156

  13. [A man with sexual disinhibition caused by paraneoplastic limbic encephalitis].

    PubMed

    de Vries, C L; Koers, H

    2013-01-01

    A 63-year-old man with symptoms of depression and sexual disinhibition was admitted to a psychiatric clinic for the elderly. Because the man’s symptoms rapidly became more severe he was referred to the emergency room. There, his illness was diagnosed as paraneoplastic limbic encephalitis with positive anti-Hu antibodies; this is a paraneoplastic neurological syndrome presenting with short-term memory loss, epileptic seizures and psychiatric symptoms. For the prognosis of the illness it is essential that the syndrome is diagnosed as early as possible. Since patients sometimes present with mainly psychiatric symptoms it is important that psychiatrists are fully informed about the symptoms and are able to make an accurate diagnosis. PMID:23408365

  14. Dissociation of brain areas associated with force production and stabilization during manipulation of unstable objects

    PubMed Central

    de Manzano, Örjan; Vollmer, Brigitte; Forsman, Lea; Valero-Cuevas, Francisco J.; Ullén, Fredrik; Forssberg, Hans

    2014-01-01

    Multifinger dexterous manipulation of unstable or deformable objects requires control of both direction and magnitude of fingertip force vectors. Our aim was to study the neuroanatomical correlates of these two distinct control functions. Brain activity was measured using functional magnetic resonance imaging while 16 male subjects (age: 26–42, M = 32, SD ± 4 years) compressed four springs representing a 2 × 2 factorial design with two levels of force and instability requirements. Significant activations associated with higher instability were located bilaterally in the precentral gyri, the postcentral gyrus, and the cerebellum. In the main effect for high force, activity was found in areas located in the primary motor regions contralateral to the active hand and bilaterally in the cerebellum. An overlap in activation between the two main effects was found bilaterally in the cerebellum (lobule VI). This study not only confirms a recently described bilateral fronto-parieto-cerebellar network for manipulation of increasingly unstable objects, but critically extends our understanding by describing its differentiated modulation with both force magnitude and instability requirements. Our results, therefore, expose a previously unrecognized and context-sensitive system of brain regions that enable dexterous manipulation for different force magnitude and instability requirements of the task. PMID:22038714

  15. Blood brain barrier breakdown was found in non-infarcted area after 2-h MCAO.

    PubMed

    Wang, Xiaona; Liu, Yushan; Sun, Yanyun; Liu, Wenlan; Jin, Xinchun

    2016-04-15

    The blood brain barrier (BBB) could be damaged within the thrombolytic time window and is considered to be a precursor to hemorrhagic transformation during reperfusion. Although we have recently reported the association between BBB damage and tissue injury within the thrombolytic time window, our knowledge about this early BBB damage is limited. In this study, rats were subjected to 2-h middle cerebral artery occlusion (MCAO) followed by 10 min reperfusion with Evan's blue as a tracer to detect BBB damage. Rat brain was sliced into 10 consecutive sections and with TTC staining, a macro and full view of the spatial distribution of BBB damage and tissue injury could be clearly seen in the same group of animals. After 2-h MCAO, tissue injury started from 2nd slice and the BBB leakage started from the 5th slice, of note, there is no colocalization between BBB damage and tissue injury. Fluoro Jade B was employed to explore the localization of neuronal degeneration, and our results showed that 2-h MCAO produced greater number of positive cells in ischemic cortex and dorsal striatum than other areas. More important, 2-h MCAO induced occludin but not claudin-5 degradation in the ischemic hemisphere and pretreatment with MMP inhibitor GM6001 significantly reduced occludin degradation as well as BBB damage detected by IgG leakage. Taken together, our findings demonstrated a "mismatch" between ischemic tissue injury and BBB leakage and a differential degradation of occludin and claudin-5 by MMP-2 after 2-h MCAO. PMID:27000223

  16. 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. PMID:16316688

  17. 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. PMID:26649203

  18. 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

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

    MedlinePlus

    ... tinnitus than others. They propose that the limbic system—a linked network of brain structures involved in emotion, behavior, and long-term memory—acts as a gatekeeper to keep the tinnitus ...

  20. BRAIN STRUCTURE. Cortical folding scales universally with surface area and thickness, not number of neurons.

    PubMed

    Mota, Bruno; Herculano-Houzel, Suzana

    2015-07-01

    Larger brains tend to have more folded cortices, but what makes the cortex fold has remained unknown. We show that the degree of cortical folding scales uniformly across lissencephalic and gyrencephalic species, across individuals, and within individual cortices as a function of the product of cortical surface area and the square root of cortical thickness. This relation is derived from the minimization of the effective free energy associated with cortical shape according to a simple physical model, based on known mechanisms of axonal elongation. This model also explains the scaling of the folding index of crumpled paper balls. We discuss the implications of this finding for the evolutionary and developmental origin of folding, including the newfound continuum between lissencephaly and gyrencephaly, and for pathologies such as human lissencephaly. PMID:26138976

  1. Semantic brain areas are involved in gesture comprehension: An electrical neuroimaging study.

    PubMed

    Proverbio, Alice Mado; Gabaro, Veronica; Orlandi, Andrea; Zani, Alberto

    2015-08-01

    While the mechanism of sign language comprehension in deaf people has been widely investigated, little is known about the neural underpinnings of spontaneous gesture comprehension in healthy speakers. Bioelectrical responses to 800 pictures of actors showing common Italian gestures (e.g., emblems, deictic or iconic gestures) were recorded in 14 persons. Stimuli were selected from a wider corpus of 1122 gestures. Half of the pictures were preceded by an incongruent description. ERPs were recorded from 128 sites while participants decided whether the stimulus was congruent. Congruent pictures elicited a posterior P300 followed by late positivity, while incongruent gestures elicited an anterior N400 response. N400 generators were investigated with swLORETA reconstruction. Processing of congruent gestures activated face- and body-related visual areas (e.g., BA19, BA37, BA22), the left angular gyrus, mirror fronto/parietal areas. The incongruent-congruent contrast particularly stimulated linguistic and semantic brain areas, such as the left medial and the superior temporal lobe. PMID:26011745

  2. 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

  3. 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

  4. Fibromyalgia Is Associated with Decreased Connectivity Between Pain- and Sensorimotor Brain Areas

    PubMed Central

    Martinsen, Sofia; Löfgren, Monika; Bileviciute-Ljungar, Indre; Kosek, Eva; Fransson, Peter

    2014-01-01

    Abstract Fibromyalgia (FM) is a syndrome characterized by chronic pain without known peripheral causes. Previously, we have reported dysfunctional pain inhibitory mechanisms for FM patients during pain administration. In this study we employed a seed correlation analysis, independent component analysis (ICA), and an analysis of fractional amplitude of low frequency fluctuations (fALFF) to study differences between a cohort of female FM patients and an age- and sex-matched healthy control group during a resting-state condition. FM patients showed decreased connectivity between thalamus and premotor areas, between the right insula and primary sensorimotor areas, and between supramarginal and prefrontal areas. Individual sensitivity to painful pressure was associated with increased connectivity between pain-related regions (e.g., insula and thalamus) and midline regions of the default mode network (including posterior cingulate cortex and medial prefrontal cortex) among patients and controls. However, neither ICA nor fALFF revealed any group differences. Our findings suggest that abnormal connectivity patterns between pain-related regions and the remaining brain during rest reflect an impaired central mechanism of pain modulation in FM. Weaker coupling between pain regions and prefrontal- and sensorimotor areas might indicate a less efficient system level control of pain circuits. Moreover, our results show that multiple, complementary analytical approaches are valuable for obtaining a more comprehensive characterization of deviant resting-state activity. In conclusion, our findings show that FM primarily is associated with decreased connectivity, for example, between several pain-related areas and sensorimotor regions, which could reflect a deficiency in pain regulation. PMID:24998297

  5. High-field MRI reveals an acute impact on brain function in survivors of the magnitude 8.0 earthquake in China

    PubMed Central

    Lui, Su; Huang, Xiaoqi; Chen, Long; Tang, Hehan; Zhang, Tijiang; Li, Xiuli; Li, Dongming; Kuang, Weihong; Chan, Raymond C.; Mechelli, Andrea; Sweeney, John A.; Gong, Qiyong

    2009-01-01

    Besides the enormous medical and economic consequences, national disasters, such as the Wenchuan 8.0 earthquake, also pose a risk to the mental health of survivors. In this context, a better understanding is needed of how functional brain systems adapt to severe emotional stress. Previous animal studies have demonstrated the importance of limbic, paralimbic, striatal, and prefrontal structures in stress and fear responses. Human studies, which have focused primarily on patients with clinically established posttraumatic stress disorders, have reported abnormalities in similar brain structures. At present, little is known about potential alterations of brain function in trauma survivors shortly after traumatic events. Here, we show alteration of brain function in a cohort of healthy survivors within 25 days after the Wenchuan earthquake by a recently discovered method known as “resting-state” functional MRI. The current investigation demonstrates that regional activity in frontolimbic and striatal areas increased significantly and connectivity among limbic and striatal networks was attenuated in our participants who had recently experienced severe emotional trauma. Trauma victims also had a reduced temporal synchronization within the “default mode” of resting-state brain function, which has been characterized in humans and other species. Taken together, our findings provide evidence that significant alterations in brain function, similar in many ways to those observed in posttraumatic stress disorders, can be seen shortly after major traumatic experiences, highlighting the need for early evaluation and intervention for trauma survivors. PMID:19720989

  6. Distribution of corticotropin-releasing factor receptors in primate brain

    SciTech Connect

    Millan, M.A.; Jacobowitz, D.M.; Hauger, R.L.; Catt, K.J.; Aguilera, G.

    1986-03-01

    The distribution and properties of receptors for corticotropin-releasing factor (CRF) were analyzed in the brain of cynomolgus monkeys. Binding of (/sup 125/I)tyrosine-labeled ovine CRF to frontal cortex and amygdala membrane-rich fractions was saturable, specific, and time- and temperature-dependent, reaching equilibrium in 30 min at 23/sup 0/C. Scatchard analysis of the binding data indicated one class of high-affinity sites with a K/sub d/ of 1 nM and a concentration of 125 fmol/mg. As in the rat pituitary and brain, CRF receptors in monkey cerebral cortex and amygdala were coupled to adenylate cyclase. Autoradiographic analysis of specific CRF binding in brain sections revealed that the receptors were widely distributed in the cerebral cortex and limbic system. Receptor density was highest in the pars tuberalis of the pituitary and throughout the cerebral cortex, specifically in the prefrontal, frontal, orbital, cingulate, insular, and temporal areas, and in the cerebellar cortex. A low binding density was present in the superior colliculus, locus coeruleus, substantia gelatinosa, preoptic area, septal area, and bed nucleus of the stria terminalis. These data demonstrate that receptors for CRF are present within the primate brain at areas related to the central control of visceral function and behavior, suggesting that brain CRF may serve as a neurotransmitter in the coordination of endocrine and neural mechanisms involved in the response to stress.

  7. CD8+ T Cell-Mediated Neuronal Dysfunction and Degeneration in Limbic Encephalitis

    PubMed Central

    Ehling, Petra; Melzer, Nico; Budde, Thomas; Meuth, Sven G.

    2015-01-01

    Autoimmune inflammation of the limbic gray matter structures of the human brain has recently been identified as major cause of mesial temporal lobe epilepsy with interictal temporal epileptiform activity and slowing of the electroencephalogram, progressive memory disturbances, as well as a variety of other behavioral, emotional, and cognitive changes. Magnetic resonance imaging exhibits volume and signal changes of the amygdala and hippocampus, and specific anti-neuronal antibodies binding to either intracellular or plasma membrane neuronal antigens can be detected in serum and cerebrospinal fluid. While effects of plasma cell-derived antibodies on neuronal function and integrity are increasingly becoming characterized, potentially contributing effects of T cell-mediated immune mechanisms remain poorly understood. CD8+ T cells are known to directly interact with major histocompatibility complex class I-expressing neurons in an antigen-specific manner. Here, we summarize current knowledge on how such direct CD8+ T cell–neuron interactions may impact neuronal excitability, plasticity, and integrity on a single cell and network level and provide an overview on methods to further corroborate the in vivo relevance of these mechanisms mainly obtained from in vitro studies. PMID:26236280

  8. Restoring Susceptibility Induced MRI Signal Loss in Rat Brain at 9.4 T: A Step towards Whole Brain Functional Connectivity Imaging

    PubMed Central

    Li, Rupeng; Liu, Xiping; Sidabras, Jason W.; Paulson, Eric S.; Jesmanowicz, Andrzej; Nencka, Andrew S.; Hudetz, Anthony G.; Hyde, James S.

    2015-01-01

    The aural cavity magnetic susceptibility artifact leads to significant echo planar imaging (EPI) signal dropout in rat deep brain that limits acquisition of functional connectivity fcMRI data. In this study, we provide a method that recovers much of the EPI signal in deep brain. Needle puncture introduction of a liquid-phase fluorocarbon into the middle ear allows acquisition of rat fcMRI data without signal dropout. We demonstrate that with seeds chosen from previously unavailable areas, including the amygdala and the insular cortex, we are able to acquire large scale networks, including the limbic system. This tool allows EPI-based neuroscience and pharmaceutical research in rat brain using fcMRI that was previously not feasible. PMID:25844644

  9. 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

  10. Limbic Encephalitis Associated With GAD65 Antibodies: Brief Review of the Relevant literature.

    PubMed

    Gagnon, Maude-Marie; Savard, Martin

    2016-07-01

    Recently, many cases of autoimmune limbic encephalitis with positive GAD65 (glutamic acid decarboxylase) antibodies have been described in the scientific literature. However, it remains an understudied topic of great relevance to practicing neurologists. Thus, we report here a review of published cases, in English, of autoimmune limbic encephalitis with this type of antibodies, focusing on presenting symptoms and signs, associated conditions, and findings upon investigation. We also report treatment responses. We aim to offer a better description of the clinical spectrum of autoimmune limbic encephalitis associated with GAD65 antibodies as well as to expose its paraclinical features and outcome. PMID:27030381

  11. High-Resolution Mapping of Myeloarchitecture In Vivo: Localization of Auditory Areas in the Human Brain.

    PubMed

    De Martino, Federico; Moerel, Michelle; Xu, Junqian; van de Moortele, Pierre-Francois; Ugurbil, Kamil; Goebel, Rainer; Yacoub, Essa; Formisano, Elia

    2015-10-01

    The precise delineation of auditory areas in vivo remains problematic. Histological analysis of postmortem tissue indicates that the relation of areal borders to macroanatomical landmarks is variable across subjects. Furthermore, functional parcellation schemes based on measures of, for example, frequency preference (tonotopy) remain controversial. Here, we propose a 7 Tesla magnetic resonance imaging method that enables the anatomical delineation of auditory cortical areas in vivo and in individual brains, through the high-resolution visualization (0.6 × 0.6 × 0.6 mm(3)) of intracortical anatomical contrast related to myelin. The approach combines the acquisition and analysis of images with multiple MR contrasts (T1, T2*, and proton density). Compared with previous methods, the proposed solution is feasible at high fields and time efficient, which allows collecting myelin-related and functional images within the same measurement session. Our results show that a data-driven analysis of cortical depth-dependent profiles of anatomical contrast allows identifying a most densely myelinated cortical region on the medial Heschl's gyrus. Analyses of functional responses show that this region includes neuronal populations with typical primary functional properties (single tonotopic gradient and narrow frequency tuning), thus indicating that it may correspond to the human homolog of monkey A1. PMID:24994817

  12. Touching a rubber hand: feeling of body ownership is associated with activity in multisensory brain areas.

    PubMed

    Ehrsson, H Henrik; Holmes, Nicholas P; Passingham, Richard E

    2005-11-01

    In the "rubber-hand illusion," the sight of brushing of a rubber hand at the same time as brushing of the person's own hidden hand is sufficient to produce a feeling of ownership of the fake hand. We shown previously that this illusion is associated with activity in the multisensory areas, most notably the ventral premotor cortex (Ehrsson et al., 2004). However, it remains to be demonstrated that this illusion does not simply reflect the dominant role of vision and that the premotor activity does not reflect a visual representation of an object near the hand. To address these issues, we introduce a somatic rubber-hand illusion. The experimenter moved the blindfolded participant's left index finger so that it touched the fake hand, and simultaneously, he touched the participant's real right hand, synchronizing the touches as perfectly as possible. After approximately 9.7 s, this stimulation elicited an illusion that one was touching one's own hand. We scanned brain activity during this illusion and two control conditions, using functional magnetic resonance imaging. Activity in the ventral premotor cortices, intraparietal cortices, and the cerebellum was associated with the illusion of touching one's own hand. Furthermore, the rated strength of the illusion correlated with the degree of premotor and cerebellar activity. This finding suggests that the activity in these areas reflects the detection of congruent multisensory signals from one's own body, rather than of visual representations. We propose that this could be the mechanism for the feeling of body ownership. PMID:16280594

  13. 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

  14. Limbic responses to reward cues correlate with antisocial trait density in heavy drinkers

    PubMed Central

    Oberlin, Brandon G.; Dzemidzic, Mario; Bragulat, Veronique; Lehigh, Cari A.; Talavage, Thomas; O’Connor, Sean J.; Kareken, David A.

    2012-01-01

    Antisocial traits are common among alcoholics— particularly in certain subtypes. Although people with antisocial tendencies show atypical brain activation in some emotion and reward paradigms, how the brain reward systems of heavy drinkers (HD) are influenced by antisocial traits remains unclear. We used subjects’ preferred alcohol drink odors (AO), appetitive (ApCO) and non-appetitive (NApO) control odors in functional magnetic resonance imaging (fMRI) to determine if reward system responses varied as a function of antisocial trait density (ASD). In this retrospective analysis, we examined 30 HD who had participated in imaging twice: once while exposed to clamped intravenous alcohol infusion targeted to 50 mg%, and once during placebo saline infusion. Under placebo, there were positive correlations between ASD and blood oxygenation level dependent (BOLD) activation in the [AO > ApCO] contrast in the left dorsal putamen, while negative correlations were present in medial orbitofrontal cortex (OFC) and the bilateral amygdala. A similar pattern was observed in the correlation with the [AO > NApO] contrast. This inverse relationship between ASD and activation to alcohol odors in OFC and amygdala was specific to AO. However, negative correlations between ASD and the [ApCO > NApO] contrast were also present in the insula, putamen, and medial frontal cortex. These data suggest that frontal and limbic reward circuits of those with significant ASD are less responsive to reward cues in general, and particularly to alcohol cues in medial OFC and amygdala. These findings are broadly consistent with the reward deficiency syndrome hypothesis, although positive correlation in the striatum suggests regional variability. PMID:22227139

  15. The auditory and non-auditory brain areas involved in tinnitus. An emergent property of multiple parallel overlapping subnetworks.

    PubMed

    Vanneste, Sven; De Ridder, Dirk

    2012-01-01

    Tinnitus is the perception of a sound in the absence of an external sound source. It is characterized by sensory components such as the perceived loudness, the lateralization, the tinnitus type (pure tone, noise-like) and associated emotional components, such as distress and mood changes. Source localization of quantitative electroencephalography (qEEG) data demonstrate the involvement of auditory brain areas as well as several non-auditory brain areas such as the anterior cingulate cortex (dorsal and subgenual), auditory cortex (primary and secondary), dorsal lateral prefrontal cortex, insula, supplementary motor area, orbitofrontal cortex (including the inferior frontal gyrus), parahippocampus, posterior cingulate cortex and the precuneus, in different aspects of tinnitus. Explaining these non-auditory brain areas as constituents of separable subnetworks, each reflecting a specific aspect of the tinnitus percept increases the explanatory power of the non-auditory brain areas involvement in tinnitus. Thus, the unified percept of tinnitus can be considered an emergent property of multiple parallel dynamically changing and partially overlapping subnetworks, each with a specific spontaneous oscillatory pattern and functional connectivity signature. PMID:22586375

  16. 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

  17. 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

  18. Thalamic changes in mesial temporal sclerosis: a limbic system pathology. A case report.

    PubMed

    Caranci, F; Bartiromo, F; Cirillo, L; Aiello, A; Cirillo, S; Brunetti, A

    2007-04-30

    Hippocampal abnormalities correlated with mesial temporal sclerosis (MTS) are well documented. MTS may be associated with extrahippocampal anomalies involving limbic structures along a known neuroanatomic pathway (Papez circuit). We report a patient with MTS and thalamic changes. Seizure-related thalamic damage could have been caused by abnormal electric discharges from the mamillary body to the anterior thalamus through the mamillothalamic tract. This suggests that MTS is not limited to the temporal lobe but could represent a limbic system pathology. PMID:24299648

  19. Habituation of human limbic neuronal response to sensory stimulation.

    PubMed

    Wilson, C L; Babb, T L; Halgren, E; Wang, M L; Crandall, P H

    1984-04-01

    Hippocampal, parahippocampal gyrus, and amygdalar neuronal responses to visual and acoustic stimuli were analyzed during trains of several hundred stimulus repetitions as part of an investigation of sensory pathways to medial temporal lobe structures in complex-partial epilepsy patients who were being monitored with depth electrodes. Ten percent of more than 500 single and multiple units tested were responsive to simple sensory stimuli. The majority of the responsive units were recorded in the posterior parahippocampal gyrus (HG) during visual stimulation. Although neurons in pes hippocampi (PH; Ammons's horn) were also responsive to photic stimuli, no visually responsive units were found in amygdala. Very few units were responsive to acoustic stimuli, and these were found only in PH and amygdala, and not in HG. Significant trends of increase or decrease in response amplitude during trains of stimuli were found in all acoustically responsive units. Significant trends of visual response amplitude increase or decrease were found in 20% of PH units, and in 44% of HG units. Mean latencies of acoustically responsive units were longer than those of visually responsive units, and latencies of PH sensory units showing decremental response were longer than nondecremental PH units. Rate of response decrement was usually linear for acoustic responses and exponential for visual responses. The response dynamics of medial temporal lobe neurons are compared with those described in the animal limbic system and are related to habituation of human sensory evoked scalp potentials. PMID:6705888

  20. The stomach-brain axis.

    PubMed

    Holtmann, Gerald; Talley, Nicholas J

    2014-12-01

    The stomach has distinct functions in relation to the ingestion and handling of solids and liquids. These functions include storage of the food before it is gradually emptied into the duodenum, mechanical crushing of larger food particles to increase the surface area, secretion of an acidic enzyme rich gastric juice and mixing the ingested food with the gastric juice. In addition, the stomach 'senses' the composition of the gastric content and this information is passed via the vagal nerve to the lateral hypothalamus and the limbic system, most likely as palatability signals that influence eating behaviour. Other sensory qualities related to the stimulation of gastric tension receptors are satiety and fullness. Receptors that respond to macronutrient content or gastric wall tension influence appetite and meal related hormone responses. The ingestion of food - in contrast to an infusion of nutrients into the stomach - has distinct effects on the activation of specific brain regions. Brain areas such as thalamus, amygdala, putamen and praecuneus are activated by the ingestion of food. Gastric nutrient infusion evokes greater activation in the hippocampus and anterior cingulate. The brain integrates these interrelated neural and hormonal signals arising from the stomach as well as visual, olfactory and anticipatory stimuli that ultimately influence eating and other behavioural patterns. Furthermore, there is now good evidence from experimental studies that gastric afferents influence mood, and animal studies point towards the possibility that gastric dysfunction may be a risk factor for mood disorders such as anxiety and depression. The stomach is also not only colonised by Helicobacter pylori but a large array of bacteria. While there is sufficient evidence to suggest that H. pylori may alter caloric intake and mood, the role of other gastric microbiome for the brain function is unknown. To address this appropriate targeted gastric microbiome studies would be

  1. Search for a threatening target triggers limbic guidance of spatial attention.

    PubMed

    Mohanty, Aprajita; Egner, Tobias; Monti, Jim M; Mesulam, M-Marsel

    2009-08-26

    The ability to actively locate potential threats in our environment is highly adaptive. To investigate mediating neural mechanisms, we designed a visual search task in which central cues signaled future location and emotional expression (angry or neutral) of a target face. Cues predicting angry targets accelerated subsequent attention shifts, indicating that endogenous signals predicting threatening events can prime the spatial attention network. Functional imaging showed that spatially informative cues activated the fusiform gyrus (FG) as well as frontoparietal components of the spatial attention network, including intraparietal sulcus (IPS) and frontal eye field (FEF), whereas cues predicting angry faces also activated limbic areas, including the amygdala. Anatomically overlapping, additive effects of spatial and emotional cuing were identified in the IPS, FEFs, and FG, regions that also displayed augmented connectivity with the amygdala after cues predicting angry faces. These data highlight a key role for the frontoparietal spatial attention network in the compilation of a salience map that combines the spatial coordinates of an event with its motivational relevance. Furthermore, they suggest that active search for a threatening stimulus elicits amygdala input to the spatial attention network and inferotemporal visual areas, facilitating the rapid detection of upcoming motivationally significant events. PMID:19710309

  2. Search for a Threatening Target Triggers Limbic Guidance of Spatial Attention

    PubMed Central

    Mohanty, Aprajita; Egner, Tobias; Monti, Jim M.; Mesulam, M.-Marsel

    2015-01-01

    The ability to actively locate potential threats in our environment is highly adaptive. To investigate mediating neural mechanisms, we designed a visual search task in which central cues signaled future location and emotional expression (angry or neutral) of a target face. Cues predicting angry targets accelerated subsequent attention shifts, indicating that endogenous signals predicting threatening events can prime the spatial attention network. Functional imaging showed that spatially informative cues activated the fusiform gyrus (FG) as well as frontoparietal components of the spatial attention network, including intraparietal sulcus (IPS) and frontal eye field (FEF), whereas cues predicting angry faces also activated limbic areas, including the amygdala. Anatomically overlapping, additive effects of spatial and emotional cuing were identified in the IPS, FEFs, and FG, regions that also displayed augmented connectivity with the amygdala after cues predicting angry faces. These data highlight a key role for the frontoparietal spatial attention network in the compilation of a salience map that combines the spatial coordinates of an event with its motivational relevance. Furthermore, they suggest that active search for a threatening stimulus elicits amygdala input to the spatial attention network and inferotemporal visual areas, facilitating the rapid detection of upcoming motivationally significant events. PMID:19710309

  3. Brain responses to food and weight loss.

    PubMed

    Behary, Preeshila; Miras, Alexander D

    2014-09-01

    In this symposium report, we examine how functional neuroimaging has revolutionized the study of human eating behaviour. In the last 20 years, functional magnetic resonance and positron emission tomography techniques have enabled researchers to understand how the human brain regions that control homeostatic and hedonic eating respond to food in physiological and pathological states. Hypothalamic, brainstem, limbic and cortical brain areas form part of a well-co-ordinated brain system that responds to central and peripheral neuronal, hormonal and nutrient signals. Even in physiological conditions, it promotes the consumption of energy-dense food, because this is advantageous in evolutionary terms. Its function is dysregulated in the context of obesity so as to promote weight gain and resist weight loss. Pharmacological and bariatric surgical interventions might be more successful than lifestyle interventions in inducing weight loss and maintenance because, unlike dieting, they reduce not only hunger but also the reward value of food through their actions in homeostatic and hedonic brain regions. Functional neuroimaging is a research tool that cannot be used in isolation; its findings become meaningful and useful only when combined with data from direct measures of eating behaviour. The neuroimaging technology is continuously improving and is expected to contribute further to the in-depth understanding of the obesity phenotype and accelerate the development of more effective and safer treatments for the condition. PMID:25210111

  4. Increases of CCK mRNA and peptide in different brain areas following acute and chronic administration of morphine.

    PubMed

    Ding, X Z; Bayer, B M

    1993-10-15

    The present study examined whether either acute or chronic administration of morphine resulted in changes in the content of CCK mRNA and CCK immunoactive peptide in selective areas of the rat brain and spinal cord. Two hours after a single injection of morphine (10 mg/kg, s.c.), CCK mRNA significantly increased in the hypothalamus (0.8-fold) and spinal cord (2-fold) relative to the CCK mRNA content in saline-injected controls. No significant differences in CCK mRNA were observed in the frontal cortex, hippocampus, midbrain or brainstem. There were no significant alterations in CCK immunoreactivity in any brain regions and spinal cord after the acute treatment with morphine. Upon repeated morphine administration, the content of CCK mRNA in both the hypothalamus and the spinal cord was further elevated by at least 3-fold. A significant increase of CCK mRNA content in brain stem (2.8-fold) was also observed following chronic morphine administration. In contrast to the acute exposure to morphine, chronic administration resulted in significant increases in CCK immunoactive peptide in hypothalamus (2.6-fold), spinal cord (2.1-fold) and brainstem (1.6-fold), but not in the other brain areas. These results demonstrate that morphine, especially following repeated administrations, stimulates endogenous CCK biosynthesis in selective brain regions. PMID:8242392

  5. Hyper-resting brain entropy within chronic smokers and its moderation by Sex

    PubMed Central

    Li, Zhengjun; Fang, Zhuo; Hager, Nathan; Rao, Hengyi; Wang, Ze

    2016-01-01

    Cigarette smoking is a chronic relapsing brain disorder, and remains a premier cause of morbidity and mortality. Functional neuroimaging has been used to assess differences in the mean strength of brain activity in smokers’ brains, however less is known about the temporal dynamics within smokers’ brains. Temporal dynamics is a key feature of a dynamic system such as the brain, and may carry information critical to understanding the brain mechanisms underlying cigarette smoking. We measured the temporal dynamics of brain activity using brain entropy (BEN) mapping and compared BEN between chronic non-deprived smokers and non-smoking controls. Because of the known sex differences in neural and behavioral smoking characteristics, comparisons were also made between males and females. Associations between BEN and smoking related clinical measures were assessed in smokers. Our data showed globally higher BEN in chronic smokers compared to controls. The escalated BEN was associated with more years of smoking in the right limbic area and frontal region. Female nonsmokers showed higher BEN than male nonsmokers in prefrontal cortex, insula, and precuneus, but the BEN sex difference in smokers was less pronounced. These findings suggest that BEN mapping may provide a useful tool for probing brain mechanisms related to smoking. PMID:27377552

  6. Hyper-resting brain entropy within chronic smokers and its moderation by Sex.

    PubMed

    Li, Zhengjun; Fang, Zhuo; Hager, Nathan; Rao, Hengyi; Wang, Ze

    2016-01-01

    Cigarette smoking is a chronic relapsing brain disorder, and remains a premier cause of morbidity and mortality. Functional neuroimaging has been used to assess differences in the mean strength of brain activity in smokers' brains, however less is known about the temporal dynamics within smokers' brains. Temporal dynamics is a key feature of a dynamic system such as the brain, and may carry information critical to understanding the brain mechanisms underlying cigarette smoking. We measured the temporal dynamics of brain activity using brain entropy (BEN) mapping and compared BEN between chronic non-deprived smokers and non-smoking controls. Because of the known sex differences in neural and behavioral smoking characteristics, comparisons were also made between males and females. Associations between BEN and smoking related clinical measures were assessed in smokers. Our data showed globally higher BEN in chronic smokers compared to controls. The escalated BEN was associated with more years of smoking in the right limbic area and frontal region. Female nonsmokers showed higher BEN than male nonsmokers in prefrontal cortex, insula, and precuneus, but the BEN sex difference in smokers was less pronounced. These findings suggest that BEN mapping may provide a useful tool for probing brain mechanisms related to smoking. PMID:27377552

  7. Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin.

    PubMed

    Bernasconi, Fosco; Schmidt, André; Pokorny, Thomas; Kometer, Michael; Seifritz, Erich; Vollenweider, Franz X

    2014-12-01

    Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control. PMID:23861318

  8. 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

    2015-01-01

    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. PMID:25973686

  9. Fat/carbohydrate ratio but not energy density determines snack food intake and activates brain reward areas

    PubMed Central

    Hoch, Tobias; Kreitz, Silke; Gaffling, Simone; Pischetsrieder, Monika; Hess, Andreas

    2015-01-01

    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. PMID:25973686

  10. Bilinguals Use Language-Control Brain Areas More Than Monolinguals to Perform Non-Linguistic Switching Tasks

    PubMed Central

    Rodríguez-Pujadas, Aina; Sanjuán, Ana; Ventura-Campos, Noelia; Román, Patricia; Martin, Clara; Barceló, Francisco; Costa, Albert; Ávila, 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. PMID:24058456

  11. Default network connectivity decodes brain states with simulated microgravity.

    PubMed

    Zeng, Ling-Li; Liao, Yang; Zhou, Zongtan; Shen, Hui; Liu, Yadong; Liu, Xufeng; Hu, Dewen

    2016-04-01

    With great progress of space navigation technology, it becomes possible to travel beyond Earth's gravity. So far, it remains unclear whether the human brain can function normally within an environment of microgravity and confinement. Particularly, it is a challenge to figure out some neuroimaging-based markers for rapid screening diagnosis of disrupted brain function in microgravity environment. In this study, a 7-day -6° head down tilt bed rest experiment was used to simulate the microgravity, and twenty healthy male participants underwent resting-state functional magnetic resonance imaging scans at baseline and after the simulated microgravity experiment. We used a multivariate pattern analysis approach to distinguish the brain states with simulated microgravity from normal gravity based on the functional connectivity within the default network, resulting in an accuracy of no less than 85 % via cross-validation. Moreover, most discriminative functional connections were mainly located between the limbic system and cortical areas and were enhanced after simulated microgravity, implying a self-adaption or compensatory enhancement to fulfill the need of complex demand in spatial navigation and motor control functions in microgravity environment. Overall, the findings suggest that the brain states in microgravity are likely different from those in normal gravity and that brain connectome could act as a biomarker to indicate the brain state in microgravity. PMID:27066149

  12. Emotional speech synchronizes brains across listeners and engages large-scale dynamic brain networks

    PubMed Central

    Nummenmaa, Lauri; Saarimäki, Heini; Glerean, Enrico; Gotsopoulos, Athanasios; Jääskeläinen, Iiro P.; Hari, Riitta; Sams, Mikko

    2014-01-01

    Speech provides a powerful means for sharing emotions. Here we implement novel intersubject phase synchronization and whole-brain dynamic connectivity measures to show that networks of brain areas become synchronized across participants who are listening to emotional episodes in spoken narratives. Twenty participants' hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI) while they listened to 45-s narratives describing unpleasant, neutral, and pleasant events spoken in neutral voice. After scanning, participants listened to the narratives again and rated continuously their feelings of pleasantness–unpleasantness (valence) and of arousal–calmness. Instantaneous intersubject phase synchronization (ISPS) measures were computed to derive both multi-subject voxel-wise similarity measures of hemodynamic activity and inter-area functional dynamic connectivity (seed-based phase synchronization, SBPS). Valence and arousal time series were subsequently used to predict the ISPS and SBPS time series. High arousal was associated with increased ISPS in the auditory cortices and in Broca's area, and negative valence was associated with enhanced ISPS in the thalamus, anterior cingulate, lateral prefrontal, and orbitofrontal cortices. Negative valence affected functional connectivity of fronto-parietal, limbic (insula, cingulum) and fronto-opercular circuitries, and positive arousal affected the connectivity of the striatum, amygdala, thalamus, cerebellum, and dorsal frontal cortex. Positive valence and negative arousal had markedly smaller effects. We propose that high arousal synchronizes the listeners' sound-processing and speech-comprehension networks, whereas negative valence synchronizes circuitries supporting emotional and self-referential processing. PMID:25128711

  13. AMPA receptor antibodies in limbic encephalitis alter synaptic receptor location

    PubMed Central

    Lai, Meizan; Hughes, Ethan G.; Peng, Xiaoyu; Zhou, Lei; Gleichman, Amy J.; Shu, Huidy; Matà, Sabrina; Kremens, Daniel; Vitaliani, Roberta; Geschwind, Michael D.; Bataller, Luis; Kalb, Robert G.; Davis, Rebecca; Graus, Francesc; Lynch, David R.; Balice-Gordon, Rita; Dalmau, Josep

    2009-01-01

    Background Limbic encephalitis (LE) frequently associates with antibodies to cell surface antigens. Characterization of these antigens is important because it facilitates the diagnosis of those disorders that are treatment-responsive. We report a novel antigen of LE and the effect of patients' antibodies on neuronal cultures. Methods Clinical analysis of 10 patients with LE. Immunoprecipitation and mass spectrometry were used to identify the antigens. HEK293 cells expressing the antigens were used in immunocytochemistry and ELISA. The effect of patients' antibodies on cultures of live rat hippocampal neurons was determined with confocal microscopy. Results Median age was 60 years (38-87); 9 were women. Seven had tumors of the lung, breast or thymus. Nine patients responded to immunotherapy or oncological therapy but neurologic relapses, without tumor recurrence, were frequent and influenced the long-term outcome. One untreated patient died of LE. All patients had antibodies against neuronal cell surface antigens that by immunoprecipitation were found to be the GluR1 and GluR2 subunits of the AMPA receptor (AMPAR). HEK293 cells expressing GluR1/2 reacted with all patients' sera or CSF, providing a diagnostic test for the disorder. Application of antibodies to cultures of neurons significantly decreased the number of GluR2-containing AMPAR clusters at synapses with a smaller decrease in overall AMPAR cluster density; these effects were reversed after antibody removal. Conclusions Antibodies to GluR1/2 associate with LE that is often paraneoplastic, treatment-responsive, and has a tendency to relapse. Our findings support an antibody-mediated pathogenesis in which patients' antibodies alter the synaptic localization and number of AMPAR. PMID:19338055

  14. Cortical thinning in cognitively normal elderly cohort of 60 to 89 year old from AIBL database and vulnerable brain areas

    NASA Astrophysics Data System (ADS)

    Lin, Zhongmin S.; Avinash, Gopal; Yan, Litao; McMillan, Kathryn

    2014-03-01

    Age-related cortical thinning has been studied by many researchers using quantitative MR images for the past three decades and vastly differing results have been reported. Although results have shown age-related cortical thickening in elderly cohort statistically in some brain regions under certain conditions, cortical thinning in elderly cohort requires further systematic investigation. This paper leverages our previously reported brain surface intensity model (BSIM)1 based technique to measure cortical thickness to study cortical changes due to normal aging. We measured cortical thickness of cognitively normal persons from 60 to 89 years old using Australian Imaging Biomarkers and Lifestyle Study (AIBL) data. MRI brains of 56 healthy people including 29 women and 27 men were selected. We measured average cortical thickness of each individual in eight brain regions: parietal, frontal, temporal, occipital, visual, sensory motor, medial frontal and medial parietal. Unlike the previous published studies, our results showed consistent age-related thinning of cerebral cortex in all brain regions. The parietal, medial frontal and medial parietal showed fastest thinning rates of 0.14, 0.12 and 0.10 mm/decade respectively while the visual region showed the slowest thinning rate of 0.05 mm/decade. In sensorimotor and parietal areas, women showed higher thinning (0.09 and 0.16 mm/decade) than men while in all other regions men showed higher thinning than women. We also created high resolution cortical thinning rate maps of the cohort and compared them to typical patterns of PET metabolic reduction of moderate AD and frontotemporal dementia (FTD). The results seemed to indicate vulnerable areas of cortical deterioration that may lead to brain dementia. These results validate our cortical thickness measurement technique by demonstrating the consistency of the cortical thinning and prediction of cortical deterioration trend with AIBL database.

  15. Quantitative pharmacological analysis of 2-125I-iodomelatonin binding sites in discrete areas of the chicken brain

    SciTech Connect

    Siuciak, J.A.; Krause, D.N.; Dubocovich, M.L. )

    1991-09-01

    The authors have localized and characterized 2-125I-iodomelatonin binding sites in the chicken brain using in vitro quantitative autoradiography. Binding sites were widely distributed throughout the chicken brain, predominantly in regions associated with the visual system. The specific binding of 2-125I-iodomelatonin to discrete chicken brain areas was found to be saturable, reversible, and of high affinity. The specific binding of 2-125I-iodomelatonin (75 pm) was quantitated for 40 identifiable brain regions. Eight brain regions were chosen for binding characterization and pharmacological analysis: optic tectum, Edinger-Westphal nucleus, oculomotor nucleus, nucleus rotundus, ventral supraoptic decussation, ventrolateral geniculate nucleus, neostriatum, and ectostriatum. These regions showed no rostral-caudal gradient in 2-125I-iodomelatonin specific binding, and saturation analysis revealed a single class of high-affinity sites with KD values in the range of 33-48 pM and receptor site density (Bmax) ranging from 31 to 58 fmol/mg protein. Competition experiments carried out with various indoles revealed a similar order of pharmacological affinities in these areas: melatonin greater than 6-chloromelatonin greater than methoxyluzindole greater than N-acetylserotonin greater than luzindole much greater than 5-HT greater than 5-methoxytryptamine. The affinity constants determined by quantitative autoradiography for these compounds to compete for 2-125I-iodomelatonin binding in the optic tectum correlated well with the affinities in chicken brain membranes at 25 degrees C (r = 0.966; slope = 0.845; n = 7) and 0 degree C (r = 0.946; slope = 0.379; n = 7), chicken retinal membranes (r = 0.973; slope = 0.759; n = 7), and the potency or affinity of these compounds to affect the calcium-dependent release of 3H-dopamine from the rabbit retina (r = 0.902; slope = 0.506; n = 6).

  16. 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

  17. 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

  18. Anti-leucine-rich glioma-inactivated 1 limbic encephalitis: A case report and literature review

    PubMed Central

    LIU, JINGYAO; LI, MIN; LI, GUIBO; ZHOU, CHUNKUI; ZHANG, RENSHENG

    2016-01-01

    This study describes the case of a 41-year-old woman admitted for anterograde memory loss, right facial grimacing and right arm posturing that had begun 1 month previously. Cranial magnetic resonance-diffusion weighted imaging and -fluid-attenuated inversion recovery imaging revealed a hyperintense signal in the left hippocampus and right basal ganglia, but no contrast enhancement. An electroencephalogram revealed rhythmic sharp and slow waves and rhythmic θ build-ups in the left temporal area. Single-photon emission computed tomography showed increased regional blood flow perfusion in the left cerebral frontal lobe and the right basal ganglia. The cerebrospinal fluid was normal, with the exception of the presence of leucine-rich glioma-inactivated 1 (LGI1) antibodies, and LGI1 antibodies were also found in the blood serum. The presence of the antibodies, the faciobrachial dystonic seizures (FBDSs) and the memory loss indicated limbic encephalitis. After 3 months of immunotherapy, the patient was free from epileptic seizures and had undergone a partial memory restoration. FBDSs alone justify the immediate initiation of immunotherapy, even prior to laboratory confirmation of the disease, as early treatment limits the duration of the illness. PMID:26889260

  19. 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. PMID:24055595

  20. 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

  1. EEG Bands of Wakeful Rest, Slow-Wave and Rapid-Eye-Movement Sleep at Different Brain Areas in Rats.

    PubMed

    Jing, Wei; Wang, Yanran; Fang, Guangzhan; Chen, Mingming; Xue, Miaomiao; Guo, Daqing; Yao, Dezhong; Xia, Yang

    2016-01-01

    Accumulating evidence reveals that neuronal oscillations with various frequency bands in the brain have different physiological functions. However, the frequency band divisions in rats were typically based on empirical spectral distribution from limited channels information. In the present study, functionally relevant frequency bands across vigilance states and brain regions were identified using factor analysis based on 9 channels EEG signals recorded from multiple brain areas in rats. We found that frequency band divisions varied both across vigilance states and brain regions. In particular, theta oscillations during REM sleep were subdivided into two bands, 5-7 and 8-11 Hz corresponding to the tonic and phasic stages, respectively. The spindle activities of SWS were different along the anterior-posterior axis, lower oscillations (~16 Hz) in frontal regions and higher in parietal (~21 Hz). The delta and theta activities co-varied in the visual and auditory cortex during wakeful rest. In addition, power spectra of beta oscillations were significantly decreased in association cortex during REM sleep compared with wakeful rest. These results provide us some new insights into understand the brain oscillations across vigilance states, and also indicate that the spatial factor should not be ignored when considering the frequency band divisions in rats. PMID:27536231

  2. EEG Bands of Wakeful Rest, Slow-Wave and Rapid-Eye-Movement Sleep at Different Brain Areas in Rats

    PubMed Central

    Jing, Wei; Wang, Yanran; Fang, Guangzhan; Chen, Mingming; Xue, Miaomiao; Guo, Daqing; Yao, Dezhong; Xia, Yang

    2016-01-01

    Accumulating evidence reveals that neuronal oscillations with various frequency bands in the brain have different physiological functions. However, the frequency band divisions in rats were typically based on empirical spectral distribution from limited channels information. In the present study, functionally relevant frequency bands across vigilance states and brain regions were identified using factor analysis based on 9 channels EEG signals recorded from multiple brain areas in rats. We found that frequency band divisions varied both across vigilance states and brain regions. In particular, theta oscillations during REM sleep were subdivided into two bands, 5–7 and 8–11 Hz corresponding to the tonic and phasic stages, respectively. The spindle activities of SWS were different along the anterior-posterior axis, lower oscillations (~16 Hz) in frontal regions and higher in parietal (~21 Hz). The delta and theta activities co-varied in the visual and auditory cortex during wakeful rest. In addition, power spectra of beta oscillations were significantly decreased in association cortex during REM sleep compared with wakeful rest. These results provide us some new insights into understand the brain oscillations across vigilance states, and also indicate that the spatial factor should not be ignored when considering the frequency band divisions in rats. PMID:27536231

  3. 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

  4. Is Swimming Safe in Areas with the Freshwater 'Brain-Eating' Amoeba?

    MedlinePlus

    ... eating amoeba." The brain infection brought on by Naegleria fowleri , an amoeba that flourishes in warm open waters, ... at Southside Hospital, in Bay Shore, N.Y. Naegleria fowleri is found in warm bodies of fresh water, ...

  5. Measuring embeddedness: Hierarchical scale-dependent information exchange efficiency of the human brain connectome

    PubMed Central

    Ye, Allen Q.; Zhan, Liang; Conrin, Sean; GadElKarim, Johnson; Zhang, Aifeng; Yang, Shaolin; Feusner, Jamie D.; Kumar, Anand; Ajilore, Olusola; Leow, Alex

    2016-01-01

    This paper presents a novel approach for understanding information exchange efficiency and its decay across hierarchies of modularity, from local to global, of the structural human brain connectome. Magnetic resonance imaging techniques have allowed us to study the human brain connectivity as a graph, which can then be analyzed using a graph-theoretical approach. Collectively termed brain connectomics, these sophisticated mathematical techniques have revealed that the brain connectome, like many networks, is highly modular and brain regions can thus be organized into communities or modules. Here, using tractography-informed structural connectomes from 46 normal healthy human subjects, we constructed the hierarchical modularity of the structural connectome using bifurcating dendrograms. Moving from fine to coarse (i.e., local to global) up the connectome's hierarchy, we computed the rate of decay of a new metric that hierarchically preferentially weighs the information exchange between two nodes in the same module. By computing “embeddedness”-the ratio between nodal efficiency and this decay rate, one could thus probe the relative scale-invariant information exchange efficiency of the human brain. Results suggest that regions that exhibit high embeddedness are those that comprise the limbic system, the default mode network, and the subcortical nuclei. This supports the presence of near-decomposability overall yet relative embeddedness in select areas of the brain. The areas we identified as highly embedded are varied in function but are arguably linked in the evolutionary role they play in memory, emotion and behavior. PMID:26096223

  6. Aluminum overload increases oxidative stress in four functional brain areas of neonatal rats

    PubMed Central

    2012-01-01

    Background Higher aluminum (Al) content in infant formula and its effects on neonatal brain development are a cause for concern. This study aimed to evaluate the distribution and concentration of Al in neonatal rat brain following Al treatment, and oxidative stress in brain tissues induced by Al overload. Methods Postnatal day 3 (PND 3) rat pups (n =46) received intraperitoneal injection of aluminum chloride (AlCl3), at dosages of 0, 7, and 35 mg/kg body wt (control, low Al (LA), and high Al (HA), respectively), over 14 d. Results Aluminum concentrations were significantly higher in the hippocampus (751.0 ± 225.8 ng/g v.s. 294.9 ± 180.8 ng/g; p < 0.05), diencephalon (79.6 ± 20.7 ng/g v.s. 20.4 ± 9.6 ng/g; p < 0.05), and cerebellum (144.8 ± 36.2 ng/g v.s. 83.1 ± 15.2 ng/g; p < 0.05) in the HA group compared to the control. The hippocampus, diencephalon, cerebellum, and brain stem of HA animals displayed significantly higher levels of lipid peroxidative products (TBARS) than the same regions in the controls. However, the average superoxide dismutase (SOD) activities in the cerebral cortex, hippocampus, cerebellum, and brain stem were lower in the HA group compared to the control. The HA animals demonstrated increased catalase activity in the diencephalon, and increased glutathione peroxidase (GPx) activity in the cerebral cortex, hippocampus, cerebellum, and brain stem, compared to controls. Conclusion Aluminum overload increases oxidative stress (H2O2) in the hippocampus, diencephalon, cerebellum, and brain stem in neonatal rats. PMID:22613782

  7. Diagnostic work up for language testing in patients undergoing awake craniotomy for brain lesions in language areas.

    PubMed

    Bilotta, Federico; Stazi, Elisabetta; Titi, Luca; Lalli, Diana; Delfini, Roberto; Santoro, Antonio; Rosa, Giovanni

    2014-06-01

    Awake craniotomy is the technique of choice in patients with brain tumours adjacent to primary and accessory language areas (Broca's and Wernicke's areas). Language testing should be aimed to detect preoperative deficits, to promptly identify the occurrence of new intraoperative impairments and to establish the course of postoperative language status. Aim of this case series is to describe our experience with a dedicated language testing work up to evaluate patients with or at risk for language disturbances undergoing awake craniotomy for brain tumour resection. Pre- and intra operative testing was accomplished with 8 tests. Intraoperative evaluation was accomplished when patients were fully cooperative (Ramsey < 3). Postoperative evaluation was scheduled at early (within 21 days) and long-term follow-up (3-6 months). Twenty consecutive patients were prospectively recruited. Preoperative language testings were normal in 9 patients (45%), showed mild to moderate language deficit in 8 (40%) and severe language deficit or aphasic disorders in 3 (15%). Broca's area was identified in 15 patients, in all cases by counting arrest during stimulation and in 12 cases by naming arrest. In this article we describe our experience using a language testing work up to evaluate - pre, intra and postoperatively - patients undergoing awake craniotomy for brain tumour resection with preoperative language disturbances or at risk for postoperative language deficits. This approach allows a systematic evaluation and recording of language function status and can be accomplished even when a neuropsychologist or speech therapist are not involved in the operation crew. PMID:24195669

  8. Common brain areas engaged in false belief reasoning and visual perspective taking: a meta-analysis of functional brain imaging studies

    PubMed Central

    Schurz, Matthias; Aichhorn, Markus; Martin, Anna; Perner, Josef

    2013-01-01

    We performed a quantitative meta-analysis of functional neuroimaging studies to identify brain areas which are commonly engaged in social and visuo-spatial perspective taking. Specifically, we compared brain activation for visual-perspective taking to activation for false belief reasoning, which requires awareness of perspective to understand someone's mistaken belief about the world which contrasts with reality. In support of a previous account by Perner and Leekam (2008), our meta-analytic conjunction analysis found common activation for false belief reasoning and visual perspective taking in the left but not the right dorsal temporo-parietal junction (TPJ). This fits with the idea that the left dorsal TPJ is responsible for representing different perspectives in a domain-general fashion. Moreover, our conjunction analysis found activation in the precuneus and the left middle occipital gyrus close to the putative Extrastriate Body Area (EBA). The precuneus is linked to mental-imagery which may aid in the construction of a different perspective. The EBA may be engaged due to imagined body-transformations when another's viewpoint is adopted. PMID:24198773

  9. Deep Brain Electrical Stimulation in Epilepsy

    NASA Astrophysics Data System (ADS)

    Rocha, Luisa L.

    2008-11-01

    The deep brain electrical stimulation has been used for the treatment of neurological disorders such as Parkinson's disease, chronic pain, depression and epilepsy. Studies carried out in human brain indicate that the application of high frequency electrical stimulation (HFS) at 130 Hz in limbic structures of patients with intractable temporal lobe epilepsy abolished clinical seizures and significantly decreased the number of interictal spikes at focus. The anticonvulsant effects of HFS seem to be more effective in patients with less severe epilepsy, an effect associated with a high GABA tissue content and a low rate of cell loss. In addition, experiments using models of epilepsy indicate that HFS (pulses of 60 μs width at 130 Hz at subthreshold current intensity) of specific brain areas avoids the acquisition of generalized seizures and enhances the postictal seizure suppression. HFS is also able to modify the status epilepticus. It is concluded that the effects of HFS may be a good strategy to reduce or avoid the epileptic activity.

  10. Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

    SciTech Connect

    Constanzo, Julie; Paquette, Benoit; Charest, Gabriel; Masson-Côté, Laurence; Guillot, Mathieu

    2015-05-15

    Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brain were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife.

  11. 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. PMID:26284026

  12. The Limbic System Conception and Its Historical Evolution

    PubMed Central

    Roxo, Marcelo R.; Franceschini, Paulo R.; Zubaran, Carlos; Kleber, Fabrício D.; Sander, Josemir W.

    2011-01-01

    Throughout the centuries, scientific observers have endeavoured to extend their knowledge of the interrelationships between the brain and its regulatory control of human emotions and behaviour. Since the time of physicians such as Aristotle and Galen and the more recent observations of clinicians and neuropathologists such as Broca, Papez, and McLean, the field of affective neuroscience has matured to become the province of neuroscientists, neuropsychologists, neurologists, and psychiatrists. It is accepted that the prefrontal cortex, amygdala, anterior cingulate cortex, hippocampus, and insula participate in the majority of emotional processes. New imaging technologies and molecular biology discoveries are expanding further the frontiers of knowledge in this arena. The advancements of knowledge on the interplay between the human brain and emotions came about as the legacy of the pioneers mentioned in this field. The aim of this paper is to describe the historical evolution of the scientific understanding of interconnections between the human brain, behaviour, and emotions. PMID:22194673

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

    PubMed Central

    Landolfi, Joseph C.; Nadkarni, Mangala

    2003-01-01

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

  14. Comparing 3D Gyrification Index and area-independent curvature-based measures in quantifying neonatal brain folding

    NASA Astrophysics Data System (ADS)

    Rodriguez-Carranza, Claudia E.; Mukherjee, P.; Vigneron, Daniel; Barkovich, James; Studholme, Colin

    2007-03-01

    In this work we compare 3D Gyrification Index and our recently proposed area-independent curvature-based surface measures [26] for the in-vivo quantification of brain surface folding in clinically acquired neonatal MR image data. A meaningful comparison of gyrification across brains of different sizes and their subregions will only be possible through the quantification of folding with measures that are independent of the area of the region of analysis. This work uses a 3D implementation of the classical Gyrification Index, a 2D measure that quantifies folding based on the ratio of the inner and outer contours of the brain and which has been used to study gyral patterns in adults with schizophrenia, among other conditions. The new surface curvature-based measures and the 3D Gyrification Index were calculated on twelve premature infants (age 28-37 weeks) from which surfaces of cerebrospinal fluid/gray matter (CSF/GM) interface and gray matter/white matter (GM/WM) interface were extracted. Experimental results show that our measures better quantify folding on the CSF/GM interface than Gyrification Index, and perform similarly on the GM/WM interface.

  15. Age of second language acquisition in multilinguals has an impact on gray matter volume in language-associated brain areas

    PubMed Central

    Kaiser, Anelis; Eppenberger, Leila S.; Smieskova, Renata; Borgwardt, Stefan; Kuenzli, Esther; Radue, Ernst-Wilhelm; Nitsch, Cordula; Bendfeldt, Kerstin

    2015-01-01

    Numerous structural studies have established that experience shapes and reshapes the brain throughout a lifetime. The impact of early development, however, is still a matter of debate. Further clues may come from studying multilinguals who acquired their second language at different ages. We investigated adult multilinguals who spoke three languages fluently, where the third language was learned in classroom settings, not before the age of 9 years. Multilinguals exposed to two languages simultaneously from birth (SiM) were contrasted with multinguals who acquired their first two languages successively (SuM). Whole brain voxel based morphometry revealed that, relative to SuM, SiM have significantly lower gray matter volume in several language-associated cortical areas in both hemispheres: bilaterally in medial and inferior frontal gyrus, in the right medial temporal gyrus and inferior posterior parietal gyrus, as well as in the left inferior temporal gyrus. Thus, as shown by others, successive language learning increases the volume of language-associated cortical areas. In brains exposed early on and simultaneously to more than one language, however, learning of additional languages seems to have less impact. We conclude that – at least with respect to language acquisition – early developmental influences are maintained and have an effect on experience-dependent plasticity well into adulthood. PMID:26106338

  16. Age of second language acquisition in multilinguals has an impact on gray matter volume in language-associated brain areas.

    PubMed

    Kaiser, Anelis; Eppenberger, Leila S; Smieskova, Renata; Borgwardt, Stefan; Kuenzli, Esther; Radue, Ernst-Wilhelm; Nitsch, Cordula; Bendfeldt, Kerstin

    2015-01-01

    Numerous structural studies have established that experience shapes and reshapes the brain throughout a lifetime. The impact of early development, however, is still a matter of debate. Further clues may come from studying multilinguals who acquired their second language at different ages. We investigated adult multilinguals who spoke three languages fluently, where the third language was learned in classroom settings, not before the age of 9 years. Multilinguals exposed to two languages simultaneously from birth (SiM) were contrasted with multinguals who acquired their first two languages successively (SuM). Whole brain voxel based morphometry revealed that, relative to SuM, SiM have significantly lower gray matter volume in several language-associated cortical areas in both hemispheres: bilaterally in medial and inferior frontal gyrus, in the right medial temporal gyrus and inferior posterior parietal gyrus, as well as in the left inferior temporal gyrus. Thus, as shown by others, successive language learning increases the volume of language-associated cortical areas. In brains exposed early on and simultaneously to more than one language, however, learning of additional languages seems to have less impact. We conclude that - at least with respect to language acquisition - early developmental influences are maintained and have an effect on experience-dependent plasticity well into adulthood. PMID:26106338

  17. Area postrema, a brain circumventricular organ, is the site of antidipsogenic action of circulating atrial natriuretic peptide in eels.

    PubMed

    Tsukada, Takehiro; Nobata, Shigenori; Hyodo, Susumu; Takei, Yoshio

    2007-11-01

    Accumulating evidence indicates that circulating atrial natriuretic peptide (ANP) potently reduces excess drinking to ameliorate hypernatremia in seawater (SW) eels. However, the cerebral mechanism underlying the antidipsogenic effect is largely unknown. To localize the ANP target site in the brain, we examined the distribution of ANP receptors (NPR-A) in eel brain immunohistochemically using an antiserum specific for eel NPR-A. The immunoreactive NPR-A was localized in the capillaries of various brain regions. In addition, immunoreactive neurons were observed mostly in the medulla oblongata, including the reticular formation, glossopharyngeal-vagal motor complex, commissural nucleus of Cajal, and area postrema (AP). Trypan Blue, which binds serum albumin and does not cross the blood-brain barrier, was injected peripherally and stained the neurons in the AP but not other NPR-A immunopositive neurons. These histological data indicate that circulating ANP acts on the AP, which was further confirmed by physiological experiments. To this end, the AP in SW eels was topically destroyed by electric cauterization or were by chemical lesion of its neurons by kainic acid, and ANP (100 pmol kg(-1)) was then injected into the circulation. Both heat-coagulative and chemical lesions to the AP greatly reduced an antidipsogenic effect of ANP, but the ANP effect was retained in sham-operated eels and in those with lesions outside the AP. These results strongly suggest that the AP, a circumventricular organ without a blood-brain barrier, serves as a functional window of access for the circulating ANP to inhibit drinking in eels. PMID:17981865

  18. Prefrontal Brain Activation During Emotional Processing: A Functional Near Infrared Spectroscopy Study (fNIRS)

    PubMed Central

    Glotzbach, Evelyn; Mühlberger, Andreas; Gschwendtner, Kathrin; Fallgatter, Andreas J; Pauli, Paul; Herrmann, Martin J

    2011-01-01

    The limbic system and especially the amygdala have been identified as key structures in emotion induction and regulation. Recently research has additionally focused on the influence of prefrontal areas on emotion processing in the limbic system and the amygdala. Results from fMRI studies indicate that the prefrontal cortex (PFC) is involved not only in emotion induction but also in emotion regulation. However, studies using fNIRS only report prefrontal brain activation during emotion induction. So far it lacks the attempt to compare emotion induction and emotion regulation with regard to prefrontal activation measured with fNIRS, to exclude the possibility that the reported prefrontal brain activation in fNIRS studies are mainly caused by automatic emotion regulation processes. Therefore this work tried to distinguish emotion induction from regulation via fNIRS of the prefrontal cortex. 20 healthy women viewed neutral pictures as a baseline condition, fearful pictures as induction condition and reappraised fearful pictures as regulation condition in randomized order. As predicted, the view-fearful condition led to higher arousal ratings than the view-neutral condition with the reappraise-fearful condition in between. For the fNIRS results the induction condition showed an activation of the bilateral PFC compared to the baseline condition (viewing neutral). The regulation condition showed an activation only of the left PFC compared to the baseline condition, although the direct comparison between induction and regulation condition revealed no significant difference in brain activation. Therefore our study underscores the results of previous fNIRS studies showing prefrontal brain activation during emotion induction and rejects the hypothesis that this prefrontal brain activation might only be a result of automatic emotion regulation processes. PMID:21673974

  19. Gene expression patterns in four brain areas associate with quantitative measure of estrous behavior in dairy cows

    PubMed Central

    2011-01-01

    Background The decline noticed in several fertility traits of dairy cattle over the past few decades is of major concern. Understanding of the genomic factors underlying fertility, which could have potential applications to improve fertility, is very limited. Here, we aimed to identify and study those genes that associated with a key fertility trait namely estrous behavior, among genes expressed in four bovine brain areas (hippocampus, amygdala, dorsal hypothalamus and ventral hypothalamus), either at the start of estrous cycle, or at mid cycle, or regardless of the phase of cycle. Results An average heat score was calculated for each of 28 primiparous cows in which estrous behavior was recorded for at least two consecutive estrous cycles starting from 30 days post-partum. Gene expression was then measured in brain tissue samples collected from these cows, 14 of which were sacrificed at the start of estrus and 14 around mid cycle. For each brain area, gene expression was modeled as a function of the orthogonally transformed average heat score values using a Bayesian hierarchical mixed model. Genes whose expression patterns showed significant linear or quadratic relationships with heat scores were identified. These included genes expected to be related to estrous behavior as they influence states like socio-sexual behavior, anxiety, stress and feeding motivation (OXT, AVP, POMC, MCHR1), but also genes whose association with estrous behavior is novel and warrants further investigation. Conclusions Several genes were identified whose expression levels in the bovine brain associated with the level of expression of estrous behavior. The genes OXT and AVP play major roles in regulating estrous behavior in dairy cows. Genes related to neurotransmission and neuronal plasticity are also involved in estrous regulation, with several genes and processes expressed in mid-cycle probably contributing to proper expression of estrous behavior in the next estrus. Studying these

  20. Neurotransmitter and their metabolite concentrations in different areas of the HPRT knockout mouse brain.

    PubMed

    Tschirner, Sarah K; Gutzki, Frank; Schneider, Erich H; Seifert, Roland; Kaever, Volkhard

    2016-06-15

    Lesch-Nyhan syndrome (LNS) is characterized by uric acid overproduction and severe neurobehavioral symptoms, such as recurrent self-mutilative behavior. To learn more about the pathophysiology of the disease, we quantified neurotransmitters and their metabolites in the cerebral hemisphere, cerebellum and the medulla oblongata of HPRT knockout mice, an animal model for LNS, in comparison to the corresponding wild-type. Our analyses included l-glutamate, 4-aminobutanoic acid (GABA), acetylcholine, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, l-normetanephrine, epinephrine and l-metanephrine and were conducted via high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS). Among these neurotransmitter systems, we did not find any abnormalities in the HPRT knockout mouse brains. On one side, this might indicate that HPRT deficiency most severely affects dopamine signaling, while brain functioning based on other neurotransmitters is more or less spared. On the other hand, our findings may reflect a compensating mechanism for impaired purine salvage that protects the brain in HPRT-deficient mice but not in LNS patients. PMID:27206901

  1. Brain surgery

    MedlinePlus

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... Before surgery, the hair on part of the scalp is shaved and the area is cleaned. The doctor makes ...

  2. Quantitative radioimmunohistochemical method using (/sup 125/I)-protein A to measure the content of methionine enkephalin in discrete rat brain areas

    SciTech Connect

    Correa, F.M.; Guilhaume, S.G.; Saavedra, J.M.

    1988-11-01

    We report a quantitative radioimmunohistochemical method, using (125I)-protein A in combination with a specific antibody to methionine enkephalin (Met-enk), for determination of the content of this peptide in discrete areas of rat brain. After paraformaldehyde fixation, rat brain sections were incubated with a Met-enk polyclonal antibody, followed by incubation with (125I)-protein A. After autoradiography with 3H-sensitive Ultrofilm, optical densities (OD) were quantified by computerized microdensitometry. The OD obtained were compared to a standard curve, constructed after determination by radioimmunoassay of the Met-enk content in corresponding brain areas from adjacent tissue sections. After comparing 15 different brain areas over a ninetyfold range of concentrations, we found a linear relationship between the content of Met-enk, as determined by radioimmunoassay, and the OD generated by autoradiography. The content of Met-enk in other discrete brain areas can be quantified by interpolation of the OD determined by autoradiography in the standard curve. The method allows, for the first time, precise quantification of peptide concentrations in discrete areas and nuclei from thin sections of rat brain. This technique has a more than 100-fold higher sensitivity than classical radioimmunoassays, with the additional advantage of neuroanatomical localization. It also has the potential for application to the quantification of many other antigens present in brain and other tissues.

  3. New understanding of adolescent brain development: relevance to transitional healthcare for young people with long term conditions.

    PubMed

    Colver, Allan; Longwell, Sarah

    2013-11-01

    Whether or not adolescence should be treated as a special period, there is now no doubt that the brain changes much during adolescence. From an evolutionary perspective, the idea of an under developed brain which is not fit for purpose until adulthood is illogical. Rather, the adolescent brain is likely to support the challenges specific to that period of life. New imaging techniques show striking changes in white and grey matter between 11 and 25 years of age, with increased connectivity between brain regions, and increased dopaminergic activity in the pre-frontal cortices, striatum and limbic system and the pathways linking them. The brain is dynamic, with some areas developing faster and becoming more dominant until other areas catch up. Plausible mechanisms link these changes to cognitive and behavioural features of adolescence. The changing brain may lead to abrupt behavioural change with attendant risks, but such a brain is flexible and can respond quickly and imaginatively. Society allows adolescent exuberance and creativity to be bounded and explored in relative safety. In healthcare settings these changes are especially relevant to young people with long term conditions as they move to young adult life; such young people need to learn to manage their health conditions with the support of their healthcare providers. PMID:23986559

  4. Electroconvulsive therapy and structural neuroplasticity in neocortical, limbic and paralimbic cortex.

    PubMed

    Pirnia, T; Joshi, S H; Leaver, A M; Vasavada, M; Njau, S; Woods, R P; Espinoza, R; Narr, K L

    2016-01-01

    Electroconvulsive therapy (ECT) is a highly effective and rapidly acting treatment for severe depression. To understand the biological bases of therapeutic response, we examined variations in cortical thickness from magnetic resonance imaging (MRI) data in 29 patients scanned at three time points during an ECT treatment index series and in 29 controls at two time points. Changes in thickness across time and with symptom improvement were evaluated at high spatial resolution across the cortex and within discrete cortical regions of interest. Patients showed increased thickness over the course of ECT in the bilateral anterior cingulate cortex (ACC), inferior and superior temporal, parahippocampal, entorhinal and fusiform cortex and in distributed prefrontal areas. No changes across time occurred in controls. In temporal and fusiform regions showing significant ECT effects, thickness differed between patients and controls at baseline and change in thickness related to therapeutic response in patients. In the ACC, these relationships occurred in treatment responders only, and thickness measured soon after treatment initiation predicted the overall ECT response. ECT leads to widespread neuroplasticity in neocortical, limbic and paralimbic regions and changes relate to the extent of antidepressant response. Variations in ACC thickness, which discriminate treatment responders and predict response early in the course of ECT, may represent a biomarker of overall clinical outcome. Because post-mortem studies show focal reductions in glial density and neuronal size in patients with severe depression, ECT-related increases in thickness may be attributable to neuroplastic processes affecting the size and/or density of neurons and glia and their connections. PMID:27271858

  5. Electroconvulsive therapy and structural neuroplasticity in neocortical, limbic and paralimbic cortex

    PubMed Central

    Pirnia, T; Joshi, S H; Leaver, A M; Vasavada, M; Njau, S; Woods, R P; Espinoza, R; Narr, K L

    2016-01-01

    Electroconvulsive therapy (ECT) is a highly effective and rapidly acting treatment for severe depression. To understand the biological bases of therapeutic response, we examined variations in cortical thickness from magnetic resonance imaging (MRI) data in 29 patients scanned at three time points during an ECT treatment index series and in 29 controls at two time points. Changes in thickness across time and with symptom improvement were evaluated at high spatial resolution across the cortex and within discrete cortical regions of interest. Patients showed increased thickness over the course of ECT in the bilateral anterior cingulate cortex (ACC), inferior and superior temporal, parahippocampal, entorhinal and fusiform cortex and in distributed prefrontal areas. No changes across time occurred in controls. In temporal and fusiform regions showing significant ECT effects, thickness differed between patients and controls at baseline and change in thickness related to therapeutic response in patients. In the ACC, these relationships occurred in treatment responders only, and thickness measured soon after treatment initiation predicted the overall ECT response. ECT leads to widespread neuroplasticity in neocortical, limbic and paralimbic regions and changes relate to the extent of antidepressant response. Variations in ACC thickness, which discriminate treatment responders and predict response early in the course of ECT, may represent a biomarker of overall clinical outcome. Because post-mortem studies show focal reductions in glial density and neuronal size in patients with severe depression, ECT-related increases in thickness may be attributable to neuroplastic processes affecting the size and/or density of neurons and glia and their connections. PMID:27271858

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

    SciTech Connect

    Miletich, R.S.

    1985-01-01

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

  7. Domain-general inhibition areas of the brain are involved in language switching: fMRI evidence from trilingual speakers.

    PubMed

    de Bruin, Angela; Roelofs, Ardi; Dijkstra, Ton; Fitzpatrick, Ian

    2014-04-15

    The prevailing theory of language switching states that unbalanced bilingual speakers use inhibition to switch between their languages (Inhibitory Control or IC model; Green, 1998). Using fMRI, we examined the brain mechanisms underlying language switching and investigated the role of domain-general inhibition areas such as the right inferior frontal gyrus (rIFG) and the pre-supplementary motor area (pre-SMA). Dutch-English-German trilinguals performed a picture naming task in the MRI scanner in both a blocked-language and a mixed-language context. The rIFG and pre-SMA showed more activation for switches to the second and third language (L2 and L3) compared to non-switch trials and blocked trials. No such difference was found for switches to the first language (L1). Our results indicate that language switching recruits brain areas related to domain-general inhibition. In this way, our study supports the claim that multilinguals use inhibition to switch between their languages. PMID:24384153

  8. Increase in cocaine- and amphetamine-regulated transcript (CART) in specific areas of the mouse brain by acute caffeine administration.

    PubMed

    Cho, Jin Hee; Cho, Yun Ha; Kim, Hyo Young; Cha, Seung Ha; Ryu, Hyun; Jang, Wooyoung; Shin, Kyung Ho

    2015-04-01

    Caffeine produces a variety of behavioral effects including increased alertness, reduced food intake, anxiogenic effects, and dependence upon repeated exposure. Although many of the effects of caffeine are mediated by its ability to block adenosine receptors, it is possible that other neural substrates, such as cocaine- and amphetamine-regulated transcript (CART), may be involved in the effects of caffeine. Indeed, a recent study demonstrated that repeated caffeine administration increases CART in the mouse striatum. However, it is not clear whether acute caffeine administration alters CART in other areas of the brain. To explore this possibility, we investigated the dose- and time-dependent changes in CART immunoreactivity (CART-IR) after a single dose of caffeine in mice. We found that a high dose of caffeine (100 mg/kg) significantly increased CART-IR 2 h after administration in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), central nucleus of the amygdala (CeA), paraventricular hypothalamic nucleus (PVN), arcuate hypothalamic nucleus (Arc), and locus coeruleus (LC), and returned to control levels after 8 h. But this increase was not observed in other brain areas. In addition, caffeine administration at doses of 25 and 50 mg/kg appears to produce dose-dependent increases in CART-IR in these brain areas; however, the magnitude of increase in CART-IR observed at a dose of 50 mg/kg was similar or greater than that observed at a dose of 100 mg/kg. This result suggests that CART-IR in AcbSh, dBNST, CeA, PVN, Arc, and LC is selectively affected by caffeine administration. PMID:25820086

  9. Brain tumor - children

    MedlinePlus

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  10. Neuronal connectivity and interactions between the auditory and limbic systems. Effects of noise and tinnitus.

    PubMed

    Kraus, Kari Suzanne; Canlon, Barbara

    2012-06-01

    Acoustic experience such as sound, noise, or absence of sound induces structural or functional changes in the central auditory system but can also affect limbic regions such as the amygdala and hippocampus. The amygdala is particularly sensitive to sound with valence or meaning, such as vocalizations, crying or music. The amygdala plays a central role in auditory fear conditioning, regulation of the acoustic startle response and can modulate auditory cortex plasticity. A stressful acoustic stimulus, such as noise, causes amygdala-mediated release of stress hormones via the HPA-axis, which may have negative effects on health, as well as on the central nervous system. On the contrary, short-term exposure to stress hormones elicits positive effects such as hearing protection. The hippocampus can affect auditory processing by adding a temporal dimension, as well as being able to mediate novelty detection via theta wave phase-locking. Noise exposure affects hippocampal neurogenesis and LTP in a manner that affects structural plasticity, learning and memory. Tinnitus, typically induced by hearing malfunctions, is associated with emotional stress, depression and anatomical changes of the hippocampus. In turn, the limbic system may play a role in the generation as well as the suppression of tinnitus indicating that the limbic system may be essential for tinnitus treatment. A further understanding of auditory-limbic interactions will contribute to future treatment strategies of tinnitus and noise trauma. PMID:22440225

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

    EPA Science Inventory

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

  12. Limbic thalamus and state-dependent behavior: The paraventricular nucleus of the thalamic midline as a node in circadian timing and sleep/wake-regulatory networks.

    PubMed

    Colavito, Valeria; Tesoriero, Chiara; Wirtu, Amenu T; Grassi-Zucconi, Gigliola; Bentivoglio, Marina

    2015-07-01

    The paraventricular thalamic nucleus (PVT), the main component of the dorsal thalamic midline, receives multiple inputs from the brain stem and hypothalamus, and targets the medial prefrontal cortex, nucleus accumbens and amygdala. PVT has been implicated in several functions, especially adaptation to chronic stress, addiction behaviors and reward, mood, emotion. We here focus on the wiring and neuronal properties linking PVT with circadian timing and sleep/wake regulation, and their behavioral implications. PVT is interconnected with the master circadian pacemaker, the hypothalamic suprachiasmatic nucleus, receives direct and indirect photic input, is densely innervated by orexinergic neurons which play a key role in arousal and state transitions. Endowed with prominent wake-related Fos expression which is suppressed by sleep, and with intrinsic neuronal properties showing a diurnal oscillation unique in the thalamus, PVT could represent a station of interaction of thalamic and hypothalamic sleep/wake-regulatory mechanisms. PVT could thus play a strategic task by funneling into limbic and limbic-related targets circadian timing and state-dependent behavior information, tailoring it for cognitive performance and motivated behaviors. PMID:25479103

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

    PubMed Central

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

    2007-01-01

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

  14. [A case of limbic encephalitis with small cell lung carcinoma in which the cognitive function improved and redeteriorated during tumor therapy].

    PubMed

    Fujimoto, So; Yamaguchi, Yasuhiro; Gotanda, Hiroshi; Shiozawa, Ryosuke; Takemura, Aya; Umeda-Kameyama, Yumi; Yamamoto, Hiroshi; Iijima, Katsuya; Akishita, Masahiro; Ouchi, Yasuyoshi

    2010-01-01

    We report the findings regarding a 70-year-old man with paraneoplastic limbic encephalitis. He presented with a chief complaint of inability to recall any events. He had been well until one month before admission, and then he abruptly began to show progressive amnesia. At admission, the patient's score on the Revised Hasegawa Dementia Scale (HDS-R) showed a decline to 13/30, thus indicating the existence of severe disorientation and an impaired memory. The brain CT and EEG showed no specific abnormalities and an analysis of cerebrospinal fluid showed only a mild increase in the total protein level. A chest X-ray film revealed a mass in the right hilum, while a histological analysis of the biopsied specimen finally established a diagnosis of small cell lung carcinoma. The FDG-PET and the enhanced brain MRI showed a single small metastatic lesion in the cerebellum. After the 1st course of chemotherapy and whole brain radiation, cognitive function, especially the short-term memory, remarkably improved and the HDS-R score increased to 21/30. However, the tumor again increased in size during the 3(rd) and 4(th) courses of chemotherapy. Interestingly, cognitive function also worsened again and the score of HDS-R declined to 15/30, 20 weeks after the start of chemotherapy. Limbic encephalitis can be associated with malignant tumors, such as small cell lung carcinoma, and some reported cases have shown a cognitive improvement after tumor therapy. In our case, we also observed a reworsening of the cognitive function in association with the acquired chemoresistence. PMID:20339211

  15. Limbic associated pelvic pain: a hypothesis to explain the diagnostic relationships and features of patients with chronic pelvic pain.

    PubMed

    Fenton, Bradford W

    2007-01-01

    Limbic associated pelvic pain is a proposed pathophysiology designed to explain features commonly encountered in patients with chronic pelvic pain, including the presence of multiple pain diagnoses, the frequency of previous abuse, the minimal or discordant pathologic changes of the involved organs, the paradoxical effectiveness of many treatments, and the recurrent nature of the condition. These conditions include endometriosis, interstitial cystitis, irritable bowel syndrome, levator ani syndrome, pelvic floor tension myalgia, vulvar vestibulitis, and vulvodynia. The hypothesis is based on recent improvements in the understanding of pain processing pathways in the central nervous system, and in particular the role of limbic structures, especially the anterior cingulate cortex, hippocampus and amygdala, in chronic and affective pain perception. Limbic associated pelvic pain is hypothesized to occur in patients with chronic pelvic pain out of proportion to any demonstrable pathology (hyperalgesia), and with more than one demonstrable pain generator (allodynia), and who are susceptible to development of the syndrome. This most likely occurs as a result of childhood sexual abuse but may include other painful pelvic events or stressors, which lead to limbic dysfunction. This limbic dysfunction is manifest both as an increased sensitivity to pain afferents from pelvic organs, and as an abnormal efferent innervation of pelvic musculature, both visceral and somatic. The pelvic musculature undergoes tonic contraction as a result of limbic efferent stimulation, which produces the minimal changes found on pathological examination, and generates a further sensation of pain. The pain afferents from these pelvic organs then follow the medial pain pathway back to the sensitized, hypervigilant limbic system. Chronic stimulation of the limbic system by pelvic pain afferents again produces an efferent contraction of the pelvic muscles, thus perpetuating the cycle. This cycle is

  16. Cellular activation in limbic brain systems during social play behaviour in rats

    PubMed Central

    van Kerkhof, Linda W.M.; Trezza, Viviana; Mulder, Tessa; Gao, Ping; Voorn, Pieter; Vanderschuren, Louk J.M.J.

    2013-01-01

    Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer-peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited. Therefore, the purpose of this study was to map the neural circuits involved in social play behaviour in rats. This was achieved by examining cellular activity after social play using the immediate early gene c-fos as a marker. After a session of social play behaviour, pronounced increases in c-fos expression were observed in the medial prefrontal cortex, medial and ventral orbitofrontal cortex, dorsal striatum, nucleus accumbens core and shell, lateral amygdala, several thalamic nuclei, dorsal raphe and the pedunculopontine tegmental nucleus. Importantly, the cellular activity patterns after social play were topographically organised in this network, as indicated by play-specific correlations in c-fos activity between regions with known direct connections. These correlations suggest involvement in social play behaviour of the projections from the medial prefrontal cortex to the striatum, and of amygdala and monoaminergic inputs to frontal cortex and striatum. The analyses presented here outline a topographically organised neural network implicated in processes such as reward, motivation and cognitive control over behaviour, which mediates social play behaviour in rats. PMID:23670540

  17. Brain Responses to High-Protein Diets12

    PubMed Central

    Journel, Marion; Chaumontet, Catherine; Darcel, Nicolas; Fromentin, Gilles; Tomé, Daniel

    2012-01-01

    Proteins are suspected to have a greater satiating effect than the other 2 macronutrients. After protein consumption, peptide hormones released from the gastrointestinal tract (mainly anorexigenic gut peptides such as cholecystokinin, glucagon peptide 1, and peptide YY) communicate information about the energy status to the brain. These hormones and vagal afferents control food intake by acting on brain regions involved in energy homeostasis such as the brainstem and the hypothalamus. In fact, a high-protein diet leads to greater activation than a normal-protein diet in the nucleus tractus solitarius and in the arcuate nucleus. More specifically, neural mechanisms triggered particularly by leucine consumption involve 2 cellular energy sensors: the mammalian target of rapamycin and AMP-activated protein kinase. In addition, reward and motivation aspects of eating behavior, controlled mainly by neurons present in limbic regions, play an important role in the reduced hedonic response of a high-protein diet. This review examines how metabolic signals emanating from the gastrointestinal tract after protein ingestion target the brain to control feeding, energy expenditure, and hormones. Understanding the functional roles of brain areas involved in the satiating effect of proteins and their interactions will demonstrate how homeostasis and reward are integrated with the signals from peripheral organs after protein consumption. PMID:22585905

  18. Unique Brain Areas Associated with Abstinence Control Are Damaged in Multiply Detoxified Alcoholics

    PubMed Central

    Duka, Theodora; Trick, Leanne; Nikolaou, Kyriaki; Gray, Marcus A.; Kempton, Matthew J.; Williams, Hugh; Williams, Steven C.R.; Critchley, Hugo D.; Stephens, David N.

    2011-01-01

    Background The ability to abstain from drinking, despite incentives to imbibe, is essential to recovery from alcoholism. Methods We used an incentive conflict task to investigate ability to abstain from responding during presentations of incentive cues. Both alcoholic (n = 23) and healthy subjects (n = 22) were required to withhold responding during the simultaneous presentation of two visual stimuli in which the individual presentation allowed responding for monetary reward. Brain structures activated during performance of the task were studied using functional magnetic resonance imaging in healthy volunteers (n = 8), and changes in gray matter volume were studied in a separate group of patients (n = 29) compared with control subjects (n = 31) in regions of interest identified on functional magnetic resonance imaging. Results Abstinent alcoholic patients were severely impaired on the incentive conflict task. The impairment was greater in patients with experience of several versus a single detoxification. Healthy volunteers, during the same incentive conflict task, showed distinct patterns of brain activation (including gyrus rectus, ventromedial prefrontal cortex, and superior frontal gyrus). Reduction of gray matter volume in ventromedial prefrontal cortex and superior frontal gyrus of patients was more extensive in those with multiple detoxifications. Conclusions Performance deficits in alcoholics are associated with withdrawal-induced impairments in prefrontal subfields, which are exacerbated following repeated episodes of detoxification. Detoxification thus compromises functional and structural integrity of prefrontal cortex and may thus impair the ability to control future drinking. Performance in the incentive conflict task is a sensitive biomarker for such deficits. PMID:21612768

  19. Plasticity in Unimodal and Multimodal Brain Areas Reflects Multisensory Changes in Self-Face Identification

    PubMed Central

    Apps, Matthew A. J.; Tajadura-Jiménez, Ana; Sereno, Marty; Blanke, Olaf; Tsakiris, Manos

    2015-01-01

    Nothing provides as strong a sense of self as seeing one's face. Nevertheless, it remains unknown how the brain processes the sense of self during the multisensory experience of looking at one's face in a mirror. Synchronized visuo-tactile stimulation on one's own and another's face, an experience that is akin to looking in the mirror but seeing another's face, causes the illusory experience of ownership over the other person's face and changes in self-recognition. Here, we investigate the neural correlates of this enfacement illusion using fMRI. We examine activity in the human brain as participants experience tactile stimulation delivered to their face, while observing either temporally synchronous or asynchronous tactile stimulation delivered to another's face on either a specularly congruent or incongruent location. Activity in the multisensory right temporo-parietal junction, intraparietal sulcus, and the unimodal inferior occipital gyrus showed an interaction between the synchronicity and the congruency of the stimulation and varied with the self-reported strength of the illusory experience, which was recorded after each stimulation block. Our results highlight the important interplay between unimodal and multimodal information processing for self-face recognition, and elucidate the neurobiological basis for the plasticity required for identifying with our continuously changing visual appearance. PMID:23964067

  20. Dopamine in thelimbic regions of the human brain: normal and abnormal.

    PubMed

    Farley, I J; Price, K S; Hornykiewicz, O

    1977-01-01

    1. In the human brain, DA was found in appreciable amounts in most of the examined basal telencephalic limbic regions, with the nucleus accumbens having the highest mean level (3.38 microgram/g). In the cortical areas of the limbic lobe of Broca, DA could be measured with certainty only in the parolfactory gyrus (0.35 microgram/g). 2. In patients with Parkinson's disease, the DA concentration in the parolfactory gyrus and nucleur accumbens was markedly reduced, whereas little change was seen in the olfactory areas. Quantitatively, the DA decrease in the nucleus accumbens was of the same magnitude as in the caudate nucleus, being, in both regions, distinctly less severe than in the putamen. 3. In three cases of paranoid schizophrenia, there were no statistically significant changes of the mean levels of DA or HVA in the nucleus accumbens. However, the DA/HVA ratio was shifted noticeably in favor of HVA, possibly indicating an increase in DA turnover. This change was less pronounced in the putamen of these cases and was absent in the caudate nucleus. 4. The possibility of the substantia nigra contributing to the dopaminergic innervation of the human nucleus accumbens, as well as the significance of the observations on DA metabolism in the schizophrenic cases, is discussed. PMID:883559

  1. Opiate dependence induces network state shifts in the limbic system.

    PubMed

    Dejean, C; Boraud, T; Le Moine, C

    2013-11-01

    Among current theories of addiction, hedonic homeostasis dysregulation predicts that the brain reward systems, particularly the mesolimbic dopamine system, switch from a physiological state to a new "set point." In opiate addiction, evidence show that the dopamine system principal targets, prefrontal cortex (PFC), nucleus accumbens (NAC) and basolateral amygdala complex (BLA) also adapt to repeated drug stimulation. Here we investigated the impact of chronic morphine on the dynamics of the network of these three interconnected structures. For that purpose we performed simultaneous electrophysiological recordings in freely-moving rats subcutaneously implanted with continuous-release morphine pellets. Chronic morphine produced a shift in the network state underpinned by changes in Delta and Gamma oscillations in the LFP of PFC, NAC and BLA, in correlation to behavioral changes. However despite continuous stimulation by the drug, an apparent normalization of the network activity and state occurred after 2 days indicating large scale adaptations. Blockade of μ opioid receptors was nonetheless sufficient to disrupt this acquired new stability in morphine-dependent animals. In line with the homeostatic dysregulation theory of addiction, our study provides original direct evidence that the PFC-NAC-BLA network of the dependent brain is characterized by a de novo balance for which the drug of abuse becomes the main contributor. PMID:23911767

  2. The Spatial Attention Network Interacts with Limbic and Monoaminergic Systems to Modulate Motivation-Induced Attention Shifts

    PubMed Central

    Gitelman, Darren R.; Small, Dana M.; Mesulam, M. Marsel

    2008-01-01

    How does the human brain integrate information from multiple domains to guide spatial attention according to motivational needs? To address this question, we measured hemodynamic responses to central cues predicting locations of peripheral attentional targets (food or tool images) in a novel covert spatial attention paradigm. The motivational relevance of food-related attentional targets was experimentally manipulated via hunger and satiety. Amygdala, posterior cingulate, locus coeruleus, and substantia nigra showed selective sensitivity to food-related cues when hungry but not when satiated, an effect that did not generalize to tools. Posterior parietal cortex (PPC), including intraparietal sulcus, posterior cingulate, and the orbitofrontal cortex displayed correlations with the speed of attentional shifts that were sensitive not just to motivational state but also to the motivational value of the target. Stronger functional coupling between PPC and posterior cingulate occurred during attentional biasing toward motivationally relevant food targets. These results reveal conjoint limbic and monoaminergic encoding of motivational salience in spatial attention. They emphasize the interactive role of posterior parietal and cingulate cortices in integrating motivational information with spatial attention, a process that is critical for selective allocation of attentional resources in an environment where target position and relevance can change rapidly. PMID:18308706

  3. Exposure to smoking cues during an emotion recognition task can modulate limbic fMRI activation in cigarette smokers.

    PubMed

    Artiges, Eric; Ricalens, Emmanuel; Berthoz, Sylvie; Krebs, Marie-Odile; Penttilä, Jani; Trichard, Christian; Martinot, Jean-Luc

    2009-09-01

    Smoking cues (SCs) refer to smoking-associated environmental stimuli that may trigger craving and withdrawal symptoms, and predispose to relapse in smokers. Although previous brain imaging studies have explored neural responses to SCs, no study has characterized the effects of SCs on cerebral activity in smokers engaged in an attention-demanding cognitive task that is unrelated to smoking. Thirteen tobacco smokers and a demographically matched group of 13 healthy non-smokers participated in a fast event-related functional magnetic resonance imaging (fMRI) study that involved a visual task integrating SCs and neutral cues (NCs) during emotion recognition trials requiring a high level of attention. No significant SC-induced alterations were detected in smokers' behavioural performance. fMRI results show that non-smokers exhibited no difference between SC and NC trials; in contrast, smokers showed SC-induced widespread deactivations in a limbic, paralimbic and striatal network classically involved in addiction, and activation in the right dorsolateral prefrontal cortex. In addition, a correlation between deactivation of the right insula and the severity of smoking dependence (Fagerström test) was detected in smokers. These results suggest that the neural reactivity of smokers to SCs can be modified in the context of a cognitive challenge. This could reflect smokers' ability to inhibit cue-induced craving and may help in smoking cessation. PMID:19650816

  4. Evidence of a pathogenic role for CD8+ T cells in anti-GABAB receptor limbic encephalitis

    PubMed Central

    Golombeck, Kristin S.; Bönte, Kathrin; Mönig, Constanze; van Loo, Karen M.; Hartwig, Marvin; Schwindt, Wolfram; Widman, Guido; Lindenau, Matthias; Becker, Albert J.; Glatzel, Markus; Elger, Christian E.; Wiendl, Heinz; Meuth, Sven G.; Lohmann, Hubertus; Gross, Catharina C.

    2016-01-01

    Objectives: To characterize the cellular autoimmune response in patients with γ-aminobutyric acid (GABA)B receptor antibody–associated limbic encephalitis (GABAB-R LE). Methods: Patients underwent MRI, extensive neuropsychological assessment, and multiparameter flow cytometry of peripheral blood and CSF. Results: We identified a series of 3 cases of nonparaneoplastic GABAB-R LE and one case of paraneoplastic GABAB-R LE associated with small cell lung cancer. All patients exhibited temporal lobe epilepsy, neuropsychological deficits, and MRI findings typical of LE. Absolute numbers of CD19+ B cells, CD138+ CD19+ plasma cells, CD4+ T cells, activated HLADR+ CD4+ T cells, as well as CD8+ T cells and HLADR+ CD8+ T cells did not differ in peripheral blood but were elevated in CSF of patients with GABAB-R LE compared to controls. Augmented absolute numbers of CD138+ CD19+ plasma cells and activated HLADR+ CD8+ T cells in CSF corresponded to higher overall neuropsychological and memory deficits in patients with GABAB-R LE. A histologic specimen of one patient following selective amygdalohippocampectomy revealed perivascular infiltrates of CD138+ plasma cells and CD4+ T cells, whereas cytotoxic CD8+ T cells were detected within the brain parenchyma in close contact to neurons. Conclusion: Our data suggest a pathogenic role for CD8+ T cells in addition to the established role of plasma cell–derived autoantibodies in GABAB-R LE. PMID:27213174

  5. Functional brain microstate predicts the outcome in a visuospatial working memory task.

    PubMed

    Muthukrishnan, Suriya-Prakash; Ahuja, Navdeep; Mehta, Nalin; Sharma, Ratna

    2016-11-01

    Humans have limited capacity of processing just up to 4 integrated items of information in the working memory. Thus, it is inevitable to commit more errors when challenged with high memory loads. However, the neural mechanisms that determine the accuracy of response at high memory loads still remain unclear. High temporal resolution of Electroencephalography (EEG) technique makes it the best tool to resolve the temporal dynamics of brain networks. EEG-defined microstate is the quasi-stable scalp electrical potential topography that represents the momentary functional state of brain. Thus, it has been possible to assess the information processing currently performed by the brain using EEG microstate analysis. We hypothesize that the EEG microstate preceding the trial could determine its outcome in a visuospatial working memory (VSWM) task. Twenty-four healthy participants performed a high memory load VSWM task, while their brain activity was recorded using EEG. Four microstate maps were found to represent the functional brain state prior to the trials in the VSWM task. One pre-trial microstate map was found to determine the accuracy of subsequent behavioural response. The intracranial generators of the pre-trial microstate map that determined the response accuracy were localized to the visuospatial processing areas at bilateral occipital, right temporal and limbic cortices. Our results imply that the behavioural outcome in a VSWM task could be determined by the intensity of activation of memory representations in the visuospatial processing brain regions prior to the trial. PMID:27515287

  6. Mild Traumatic Brain Injury Decreases Broadband Power in Area CA1.

    PubMed

    Paterno, Rosalia; Metheny, Hannah; Xiong, Guoxiang; Elkind, Jaclynn; Cohen, Akiva S

    2016-09-01

    Cognitive impairment caused by traumatic brain injury (TBI) can lead to devastating consequences for both patients and their families. The underlying neurological basis for TBI-induced cognitive dysfunction remains unknown. However, many lines of research have implicated the hippocampus in the pathophysiology of TBI. In particular, past research has found that theta oscillations, long thought to be the electrophysiological basis of learning and memory, are decreased in the hippocampus post-TBI. Here, we recorded in vivo electrophysiological activity in the hippocampi of 16 mice, 8 of which had previously undergone a TBI. Consistent with previous data, we found that theta power in the hippocampus was decreased in TBI animals compared to sham controls; however, this effect was driven by changes in broadband power and not theta oscillations. This result suggests that broadband fluctuations in the hippocampal local field potential can be used as an electrophysiological surrogate of abnormal neurological activity post-TBI. PMID:26529412

  7. MRI-based surface area estimates in the normal adult human brain: evidence for structural organisation.

    PubMed Central

    Sisodiya, S; Free, S; Fish, D; Shorvon, S

    1996-01-01

    There are a number of quantitative relationships between geometric parameters describing the structure of the normal human cerebral cortex examined in vivo using volumetric magnetic resonance imaging. A voxel-counting method is used to estimate grey-white interface surface area. The effects of bias associated with the method are considered. In 33 normal controls, the cerebral hemispheres were symmetric in terms of total volume, irrespective of handedness, but not in terms of surface areas for right-handers. The surface area of the grey matter-white matter interface was directly proportional to the cortical grey matter volume, suggesting that growth of the neocortex is primarily tangential, with repetition of a basic structural element rather than gross alterations in the thickness of the cortex. The majority of the surface area of the grey-white interface lies within gyral white matter cores. The mean thickness of the cortex of the right cerebral hemisphere in vivo was 3.0 mm and that of the left 3.3 mm. There was a relationship between the cross-sectional area of the corpus callosum and grey-white interface surface area, suggesting that a fixed proportion and cortical neurons extend interhemispheric axons. These findings suggest that there are general architectural principles governing the organisation of the complex, but ordered, human cerebral cortex. Images Fig. 1 Fig. 2 PMID:8621342

  8. Architectural Representation of Valence in the Limbic System.

    PubMed

    Namburi, Praneeth; Al-Hasani, Ream; Calhoon, Gwendolyn G; Bruchas, Michael R; Tye, Kay M

    2016-06-01

    In order to thrive, animals must be able to recognize aversive and appetitive stimuli within the environment and subsequently initiate appropriate behavioral responses. This assignment of positive or negative valence to a stimulus is a key feature of emotional processing, the neural substrates of which have been a topic of study for several decades. Until recently, the result of this work has been the identification of specific brain regions, such as the basolateral amygdala (BLA) and nucleus accumbens (NAc), as important to valence encoding. The advent of modern tools in neuroscience has allowed further dissection of these regions to identify specific populations of neurons signaling the valence of environmental stimuli. In this review, we focus upon recent work examining the mechanisms of valence encoding, and provide a model for the systematic investigation of valence within anatomically-, genetically-, and functionally defined populations of neurons. PMID:26647973

  9. Vasopressin receptors in the brain, liver and kidney of rats following osmotic stimulation.

    PubMed

    Landgraf, R; Szot, P; Dorsa, D M

    1991-03-29

    The binding site concentration (Bmax) and equilibrium dissociation constant (Kd) for [3H]-arginine vasopressin (AVP) binding sites were measured in limbic brain areas (septum, dorsal hippocampus, amygdala) and liver and kidney of control and osmotically stimulated male Wistar rats. Membrane binding was performed in these five areas 30, 60 and 180 min following intraperitoneal injection of hypertonic saline. This paradigm resulted in no significant change in binding characteristics in the septum, dorsal hippocampus, amygdala and liver from control treated rats. In contrast, the kidney Bmax was significantly reduced 60 min following osmotic stimulation, with no effect on affinity. These results also suggest that AVP receptors in the CNS are relatively resistant to regulatory effects of an acute AVP exposure. PMID:1828184

  10. Correlation of the impedance and effective electrode area of doped PEDOT modified electrodes for brain-machine interfaces.

    PubMed

    Harris, Alexander R; Molino, Paul J; Kapsa, Robert M I; Clark, Graeme M; Paolini, Antonio G; Wallace, Gordon G

    2015-05-01

    Electrode impedance is used to assess the thermal noise and signal-to-noise ratio for brain-machine interfaces. An intermediate frequency of 1 kHz is typically measured, although other frequencies may be better predictors of device performance. PEDOT-PSS, PEDOT-DBSA and PEDOT-pTs conducting polymer modified electrodes have reduced impedance at 1 kHz compared to bare metal electrodes, but have no correlation with the effective electrode area. Analytical solutions to impedance indicate that all low-intermediate frequencies can be used to compare the electrode area at a series RC circuit, typical of an ideal metal electrode in a conductive solution. More complex equivalent circuits can be used for the modified electrodes, with a simplified Randles circuit applied to PEDOT-PSS and PEDOT-pTs and a Randles circuit including a Warburg impedance element for PEDOT-DBSA at 0 V. The impedance and phase angle at low frequencies using both equivalent circuit models is dependent on the electrode area. Low frequencies may therefore provide better predictions of the thermal noise and signal-to-noise ratio at modified electrodes. The coefficient of variation of the PEDOT-pTs impedance at low frequencies was lower than the other conducting polymers, consistent with linear and steady-state electroactive area measurements. There are poor correlations between the impedance and the charge density as they are not ideal metal electrodes. PMID:25773879

  11. Cortical Potentials Evoked by Deep Brain Stimulation in the Subthalamic Area

    PubMed Central

    Devergnas, Annaelle; Wichmann, Thomas

    2011-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been used since the mid-1990s as a treatment for patients with Parkinson's disease, and more recently also in other conditions, such as dystonia or obsessive compulsive disorder. Non-invasive studies of cortical evoked potentials (EPs) that follow individual STN–DBS stimuli has provided us with insights about the conduction of the DBS pulses to the cortex. Such EPs have multiple components of different latencies, making it possible to distinguish short-latency and long-latency responses (3–8 ms and 18–25 ms latency, respectively). The available evidence indicates that these short- and long-latency EPs correspond to conduction from the STN stimulation site to the cortical recording location via anti- and orthodromic pathways, respectively. In this review we survey the literature from recording studies in human patients treated with STN–DBS for Parkinson's disease and other conditions, as well as recent animal studies (including our own) that have begun to elucidate details of the pathways, frequency dependencies, and other features of EPs. In addition, we comment on the possible clinical utility of this knowledge. PMID:21625611

  12. Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study

    PubMed Central

    Bauer, M; Berman, S; Stamm, T; Plotkin, M; Adli, M; Pilhatsch, M; London, E D; Hellemann, G S; Whybrow, P C; Schlagenhauf, F

    2016-01-01

    Adding supraphysiologic doses of levothyroxine (L-T4) to standard treatment for bipolar depression shows promise, but the mechanisms underlying clinical improvement are unknown. In a previous pilot study, L-T4 treatment reduced depression scores and activity within the anterior limbic network. Here we extended this work in a randomized, double-blind, placebo-controlled study of patients with bipolar depression. Cerebral glucose metabolism was assessed with positron emission tomography and [F-18]fluorodeoxyglucose before and after 6 weeks of treatment with L-T4 (n=15) or placebo (n=10) in 12 volumes of interest (VOIs): the bilateral thalamus, amygdala, hippocampus, dorsal striatum and ventral striatum, and midline cerebellar vermis and subgenual cingulate cortex. Radioactivity in the VOIs, normalized to whole-brain radioactivity was taken as a surrogate index of glucose metabolism, and markers of thyroid function were assayed. Changes in brain activity and their association with clinical response were assessed using statistical parametric mapping. Adjunctive L-T4 treatment produced a significant decline in depression scores during the 6-week treatment. In patients treated with L-T4, we found a significant decrease in regional activity at P<0.05 after Bonferroni correction in the left thalamus, right amygdala, right hippocampus, left ventral striatum and the right dorsal striatum. Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate were correlated with a reduction in depression scores (P<0.05 after Bonferroni correction). Placebo treatment was associated with a significant decrease in activity only in the right amygdala, and no region had a change in activity that was correlated with change in depression scores. The groups differed significantly in the relationship between the changes in depression scores and in activity in the thalamus bilaterally and the left ventral striatum. The findings provide evidence that administration of

  13. Brain Regions Associated With Internalizing and Externalizing Psychiatric Symptoms in Patients With Penetrating Traumatic Brain Injury.

    PubMed

    Huey, Edward D; Lee, Seonjoo; Lieberman, Jeffrey A; Devanand, D P; Brickman, Adam M; Raymont, Vanessa; Krueger, Frank; Grafman, Jordan

    2016-01-01

    A factor structure underlying DSM-IV diagnoses has been previously reported in neurologically intact patients. The authors determined the brain regions associated with factors underlying DSM-IV diagnoses and compared the ability of DSM-IV diagnoses, factor scores, and self-report measures to account for the neuroanatomical findings in patients with penetrating brain injuries. This prospective cohort study included 254 Vietnam War veterans: 199 with penetrating brain injuries and 55 matched control participants. Measures include DSM-IV diagnoses (from a Structured Clinical Interview for DSM), self-report measures of depression and anxiety, and CT scans. Factors underlying DSM-IV diagnoses were determined using an exploratory factor analysis and correlated with percent of brain regions affected. The ability of the factor scores, DSM-IV diagnoses, and the self-report psychiatric measures to account for the anatomical variance was compared with multiple regressions. Internalizing and externalizing factors were identified in these brain-injured patients. Damage to the left amygdala and bilateral basal ganglia was associated with lower internalizing factor scores, and damage to the left medial orbitofrontal cortex (OFC) with higher, and bilateral hippocampi with lower, externalizing factor scores. Factor scores best predicted left amygdala and bilateral hippocampal involvement, whereas DSM-IV diagnoses best predicted bilateral basal ganglia and left OFC involvement. Damage to the limbic areas involved in the processing of emotional and reward information, including structures involved in the National Institute of Mental Health's Research Domain Criteria Negative Valence Domain, influences the development of internalizing and externalizing psychiatric symptoms. Self-report measures underperformed DSM-IV and factor scores in predicting neuroanatomical findings. PMID:26715034

  14. A short-term diabetes induced changes of catecholamines and p38-MAPK in discrete areas of rat brain.

    PubMed

    Ramakrishnan, R; Kempuraj, D; Prabhakaran, K; Jayakumar, A R; Devi, R S; Suthanthirarajan, N; Namasivayam, A

    2005-08-26

    Chronic diabetes is associated with the alteration of second messengers and CNS disorders. We have recently identified that protein kinases (CaMKII and PKC-alpha) and brain neurotransmitters are altered during diabetes as well as in hyperglycemic and acidotic conditions. In this study, we investigated the effects of acute diabetes on the levels of dopamine (DA), norepinephrine (NE), epinephrine (E) and p38-Mitogen-Activated Protein Kinase (p38-MAPK) in striatum (ST), hippocampus (HC), hypothalamus (HT), midbrain (MB), pons medulla (PM), cerebellum (CB) and cerebral cortex (CCX). Alloxan (45 mg/kg) diabetic untreated rats that showed hyperglycemia (>260 mg%), revealed significant increases of DA level in ST (1.5 fold), HC (2.2 fold) and PM (2.0 fold) and the E level also found to be increased significantly in HT (2.4 fold), whereas the NE level was decreased in CB (0.5 fold), after 7 days of diabetes. Immunoblotting study of p38-MAPK expression under identical conditions showed significant alterations in ST, HC, HT and PM (p<0.05) correlated with the changes of catecholamines (DA and E). On the other hand, the above changes were reversed in insulin-treated diabetic rats maintained under normal glucose level (80 -110 mg %). These results suggest that p38-MAPK may regulate the rate of either the synthesis or release of DA and E in corresponding brain areas, but not NE, under these conditions. PMID:16009379

  15. Motor imagery of hand actions: Decoding the content of motor imagery from brain activity in frontal and parietal motor areas

    PubMed Central

    Pilgramm, Sebastian; de Haas, Benjamin; Helm, Fabian; Zentgraf, Karen; Stark, Rudolf; Munzert, Jörn

    2015-01-01

    Abstract How motor maps are organized while imagining actions is an intensely debated issue. It is particularly unclear whether motor imagery relies on action‐specific representations in premotor and posterior parietal cortices. This study tackled this issue by attempting to decode the content of motor imagery from spatial patterns of Blood Oxygen Level Dependent (BOLD) signals recorded in the frontoparietal motor imagery network. During fMRI‐scanning, 20 right‐handed volunteers worked on three experimental conditions and one baseline condition. In the experimental conditions, they had to imagine three different types of right‐hand actions: an aiming movement, an extension–flexion movement, and a squeezing movement. The identity of imagined actions was decoded from the spatial patterns of BOLD signals they evoked in premotor and posterior parietal cortices using multivoxel pattern analysis. Results showed that the content of motor imagery (i.e., the action type) could be decoded significantly above chance level from the spatial patterns of BOLD signals in both frontal (PMC, M1) and parietal areas (SPL, IPL, IPS). An exploratory searchlight analysis revealed significant clusters motor‐ and motor‐associated cortices, as well as in visual cortices. Hence, the data provide evidence that patterns of activity within premotor and posterior parietal cortex vary systematically with the specific type of hand action being imagined. Hum Brain Mapp 37:81–93, 2016. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26452176

  16. Weight Gain following Pallidal Deep Brain Stimulation: A PET Study.

    PubMed

    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc

    2016-01-01

    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson's disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target. PMID:27070317

  17. Weight Gain following Pallidal Deep Brain Stimulation: A PET Study

    PubMed Central

    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc

    2016-01-01

    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi-DBS in patients with Parkinson’s disease (PD). Body mass index was calculated and brain activity prospectively measured using 2-deoxy-2[18F]fluoro-D-glucose PET four months before and four months after the start of GPi-DBS in 19 PD patients. Dopaminergic medication was included in the analysis to control for its possible influence on brain metabolism. Body mass index increased significantly by 0.66 ± 1.3 kg/m2 (p = 0.040). There were correlations between weight gain and changes in brain metabolism in premotor areas, including the left and right superior gyri (Brodmann area, BA 6), left superior gyrus (BA 8), the dorsolateral prefrontal cortex (right middle gyrus, BAs 9 and 46), and the left and right somatosensory association cortices (BA 7). However, we found no correlation between weight gain and metabolic changes in limbic and associative areas. Additionally, there was a trend toward a correlation between reduced dyskinesia and weight gain (r = 0.428, p = 0.067). These findings suggest that, unlike STN-DBS, motor improvement is the major contributing factor for weight gain following GPi-DBS PD, confirming the motor selectivity of this target. PMID:27070317

  18. Effect of Acute Emotional Stress on Proteomic Profile of Selected Brain Areas and Lysosomal Proteolysis in Rats with Different Behavioral Activity.

    PubMed

    Sharanova, N E; Kirbaeva, N V; Toropygin, I Yu; Khryapova, E V; Koplik, E V; Soto, C Kh; Pertsov, S S; Vasiliev, A V

    2016-07-01

    We compared proteome profiles of selected brain areas (cortex, amygdala, hippocampus, and reticular formation) and measured cathepsins B and D activity in liver lysosomal fraction in rats with different behavioral activity under conditions of emotional stress. In passive rats, the expression of some proteins in various brain regions was changed and baseline cathepsin B activity was higher than in active animals. Taken together, the results attest to differences in the adaptive response formation in rats, depending on behavioral features. PMID:27502534

  19. Vasopressin and noradrenaline coexistence in the rat locus ceruleus: differential decreases of their levels in distant brain areas after thermal and neurotoxic lesions.

    PubMed

    Caffé, A R; van Leeuwen, F W; Buijs, R M; van der Gugten, J

    1988-09-01

    Vasopressin (VP) and noradrenaline (NA) coexist in the rat locus ceruleus (LC). After thermal lesions of LC, however, no detectable loss of VP-immunoreactive fibers was examined in the brain. VP and NA levels were also measured in the cortex, hippocampus and cerebellum, after unilateral LC lesions. Only significant ipsilateral depletions of NA levels were found. Therefore, no indications were obtained for VP transport by LC neurons towards distant brain areas. PMID:3140998

  20. Verbal fluency deficits and altered lateralization of language brain areas in individuals genetically predisposed to schizophrenia

    PubMed Central

    Bhojraj, Tejas S; Francis, Alan N; Rajarethinam, Rajaprabhakaran; Eack, Shaun; Kulkarni, Shreedhar; Prasad, Konasale M; Montrose, Debra M; Dworakowski, Diana; Diwadkar, Vaibhav; Keshavan, Matcheri S

    2016-01-01

    Alterations of verbal fluency may correlate with deficits of gray matter volume and hemispheric lateralization of language brain regions like the pars triangularis (PT) in schizophrenia. Examining non-psychotic individuals at high genetic risk (HR) for schizophrenia may clarify if these deficits represent heritable trait markers or state dependent phenomena. We assessed adolescent and young adult HR subjects (N=60) and healthy controls (HC; N=42) using verbal fluency tests and Freesurfer to process T1-MRI scans. We hypothesized volumetric and lateralization alterations of the PT and their correlation with verbal fluency deficits. HR subjects had letter verbal fluency deficits (controlling for IQ), left PT deficits (p=.00), (controlling ICV) and reversal of the L>R PT asymmetry noted in HC. Right Heschl’s (p=.00), left supramarginal (p=.00) and right angular gyrii (p=.02) were also reduced in HR subjects. The L>R asymmetry of the Heschl’s gyrus seen in HC was exaggerated and asymmetries of L>R of supramarginal and R>L of angular gyri, seen in HC were attenuated in HR subjects. L>R asymmetry of the PT predicted better verbal fluency across the pooled HR and HC groups. Young relatives of schizophrenia patients have verbal fluency deficits, gray matter volume deficits and reversed asymmetry of the pars triangularis. A reversed structural asymmetry of the PT in HR subjects may impair expressive language abilities leading to verbal f;uency deficits. Volumetric deficits and altered asymmetry in inferior parietal and Heschl’s gyrii may accompany genetic liability to schizophrenia. PMID:19840895

  1. Norepinephrine content in discrete brain areas and neurohypophysial vasopressin in rats after a 9-d spaceflight (SLS-1)

    NASA Technical Reports Server (NTRS)

    Fareh, Jeannette; Cottet-Emard, Jean-Marie; Pequignot, Jean-Marc; Jahns, Gary; Meylor, John; Viso, Michel; Vassaux, Didier; Gauquelin, Guillemette; Gharib, Claude

    1993-01-01

    The norepinephrine (NE) content in discrete brain areas and the vasopressin content in the neurohypophysial system were assessed in rats after a 9-d spaceflight and after a recovery period. The NE content in the locus coeruleus decreased significantly in spaceflight rats, but showed no difference between control and flight animals after a 9-d recovery. These findings were probably due to an acute stress undergone during landing. The NE content was unchanged in the A2 and A5 cell groups. In rats flown aboard SLS-1, the vasopressin content was increased in the posterior pituitary, and was significantly decreased in the hypothalamus. We conclude that the NE depletion in the locus coeruleus and the alteration in vasopressin release were consistent with an acute stress, likely occurring during and/or after landing. These changes tend to mask the actual neuroendocrine modifications caused by microgravity.

  2. The metabolic effects of limbic leucotomy in Gilles de la Tourette syndrome.

    PubMed Central

    Sawle, G V; Lees, A J; Hymas, N F; Brooks, D J; Frackowiak, R S

    1993-01-01

    Regional cerebral oxygen metabolism was measured before and after limbic leucotomy in a patient with Gilles de la Tourette syndrome, obsessive compulsive disorder, and obsessional slowness. The preoperative scan showed hypermetabolism in the caudate nuclei, which normalised after operation. It is proposed that the beneficial effects of this operation on both tics and obsessive compulsive behaviour are mediated by disruption of abnormal neural activity in basal ganglia-thalamocortical loops. Images PMID:8410025

  3. Low doses of neurotensin in the preoptic area produce hyperthermia. Comparison with other brain sites and with neurotensin-induced analgesia.

    PubMed

    Benmoussa, M; Chait, A; Loric, G; de Beaurepaire, R

    1996-01-01

    High amounts of neurotensin (NT) are found in the preoptic area of the hypothalamus, an area known to be involved in the regulation of body temperature. It is generally believed that NT is a peptide that produces hypothermia, and several sites in the brain have been proposed to mediate NT-induced hypothermia, including the preoptic area. However, the doses of NT used in these experiments were always very high (microgram order) whereas, according to Goedert, the total brain content of NT in the rat does not exceed 10 ng. We therefore reinvestigated the effects of microinjections of NT in the brain, using high (5 micrograms) and low (50 and 5 ng) doses, into the preoptic area and other brain sites (cerebral ventricles, posterior hypothalamus, and nucleus accumbens), and we also studied, as a comparison, the effects of high and low doses of NT on pain sensitivity in the same sites. The results show that the preoptic area has unique properties in the regulation of body temperature: low doses of NT in the preoptic area produce a hyperthermic response, whereas high doses produce hypothermia. In comparison, NT produces hypothermia in the posterior hypothalamus whatever the dose, and NT has analgesic effects in the preoptic area only at high doses. Besides, NT has no thermic effect, but does have an analgesic effect, in the nucleus accumbens. The selectivity of the actions of high doses of NT, as well as the mechanism of action of NT (possibly an endogenous neuroleptic), are discussed. PMID:8705314

  4. Brain Mapping-Based Model of Δ(9)-Tetrahydrocannabinol Effects on Connectivity in the Pain Matrix.

    PubMed

    Walter, Carmen; Oertel, Bruno G; Felden, Lisa; Kell, Christian A; Nöth, Ulrike; Vermehren, Johannes; Kaiser, Jochen; Deichmann, Ralf; Lötsch, Jörn

    2016-05-01

    Cannabinoids receive increasing interest as analgesic treatments. However, the clinical use of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) has progressed with justified caution, which also owes to the incomplete mechanistic understanding of its analgesic effects, in particular its interference with the processing of sensory or affective components of pain. The present placebo-controlled crossover study therefore focused on the effects of 20 mg oral THC on the connectivity between brain areas of the pain matrix following experimental stimulation of trigeminal nocisensors in 15 non-addicted healthy volunteers. A general linear model (GLM) analysis identified reduced activations in the hippocampus and the anterior insula following THC administration. However, assessment of psychophysiological interaction (PPI) revealed that the effects of THC first consisted in a weakening of the interaction between the thalamus and the secondary somatosensory cortex (S2). From there, dynamic causal modeling (DCM) was employed to infer that THC attenuated the connections to the hippocampus and to the anterior insula, suggesting that the reduced activations in these regions are secondary to a reduction of the connectivity from somatosensory regions by THC. These findings may have consequences for the way THC effects are currently interpreted: as cannabinoids are increasingly considered in pain treatment, present results provide relevant information about how THC interferes with the affective component of pain. Specifically, the present experiment suggests that THC does not selectively affect limbic regions, but rather interferes with sensory processing which in turn reduces sensory-limbic connectivity, leading to deactivation of affective regions. PMID:26514581

  5. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens.

    PubMed

    Albaugh, Daniel L; Salzwedel, Andrew; Van Den Berge, Nathalie; Gao, Wei; Stuber, Garret D; Shih, Yen-Yu Ian

    2016-01-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action. PMID:27601003

  6. Functional Magnetic Resonance Imaging of Electrical and Optogenetic Deep Brain Stimulation at the Rat Nucleus Accumbens

    PubMed Central

    Albaugh, Daniel L.; Salzwedel, Andrew; Van Den Berge, Nathalie; Gao, Wei; Stuber, Garret D.; Shih, Yen-Yu Ian

    2016-01-01

    Deep brain stimulation of the nucleus accumbens (NAc-DBS) is an emerging therapy for diverse, refractory neuropsychiatric diseases. Although DBS therapy is broadly hypothesized to work through large-scale neural modulation, little is known regarding the neural circuits and networks affected by NAc-DBS. Using a healthy, sedated rat model of NAc-DBS, we employed both evoked- and functional connectivity (fc) MRI to examine the functional circuit and network changes achieved by electrical NAc stimulation. Optogenetic-fMRI experiments were also undertaken to evaluate the circuit modulation profile achieved by selective stimulation of NAc neurons. NAc-DBS directly modulated neural activity within prefrontal cortex and a large number of subcortical limbic areas (e.g., amygdala, lateral hypothalamus), and influenced functional connectivity among sensorimotor, executive, and limbic networks. The pattern and extent of circuit modulation measured by evoked-fMRI was relatively insensitive to DBS frequency. Optogenetic stimulation of NAc cell bodies induced a positive fMRI signal in the NAc, but no other detectable downstream responses, indicating that therapeutic NAc-DBS might exert its effect through antidromic stimulation. Our study provides a comprehensive mapping of circuit and network-level neuromodulation by NAc-DBS, which should facilitate our developing understanding of its therapeutic mechanisms of action. PMID:27601003

  7. Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume?

    PubMed

    Lemaitre, Herve; Goldman, Aaron L; Sambataro, Fabio; Verchinski, Beth A; Meyer-Lindenberg, Andreas; Weinberger, Daniel R; Mattay, Venkata S

    2012-03-01

    Normal aging is accompanied by global as well as regional structural changes. While these age-related changes in gray matter volume have been extensively studied, less has been done using newer morphological indexes, such as cortical thickness and surface area. To this end, we analyzed structural images of 216 healthy volunteers, ranging from 18 to 87 years of age, using a surface-based automated parcellation approach. Linear regressions of age revealed a concomitant global age-related reduction in cortical thickness, surface area and volume. Cortical thickness and volume collectively confirmed the vulnerability of the prefrontal cortex, whereas in other cortical regions, such as in the parietal cortex, thickness was the only measure sensitive to the pronounced age-related atrophy. No cortical regions showed more surface area reduction than the global average. The distinction between these morphological measures may provide valuable information to dissect age-related structural changes of the brain, with each of these indexes probably reflecting specific histological changes occurring during aging. PMID:20739099

  8. Activation Changes in Zebra Finch (Taeniopygia guttata) Brain Areas Evoked by Alterations of the Earth Magnetic Field

    PubMed Central

    Keary, Nina; Bischof, Hans-Joachim

    2012-01-01

    Many animals are able to perceive the earth magnetic field and to use it for orientation and navigation within the environment. The mechanisms underlying the perception and processing of magnetic field information within the brain have been thoroughly studied, especially in birds, but are still obscure. Three hypotheses are currently discussed, dealing with ferromagnetic particles in the beak of birds, with the same sort of particles within the lagena organs, or describing magnetically influenced radical-pair processes within retinal photopigments. Each hypothesis is related to a well-known sensory organ and claims parallel processing of magnetic field information with somatosensory, vestibular and visual input, respectively. Changes in activation within nuclei of the respective sensory systems have been shown previously. Most of these previous experiments employed intensity enhanced magnetic stimuli or lesions. We here exposed unrestrained zebra finches to either a stationary or a rotating magnetic field of the local intensity and inclination. C-Fos was used as an activity marker to examine whether the two treatments led to differences in fourteen brain areas including nuclei of the somatosensory, vestibular and visual system. An ANOVA revealed an overall effect of treatment, indicating that the magnetic field change was perceived by the birds. While the differences were too small to be significant in most areas, a significant enhancement of activation by the rotating stimulus was found in a hippocampal subdivision. Part of the hyperpallium showed a strong, nearly significant, increase. Our results are compatible with previous studies demonstrating an involvement of at least three different sensory systems in earth magnetic field perception and suggest that these systems, probably less elaborated, may also be found in nonmigrating birds. PMID:22679515

  9. Development traumatic brain injury computer user interface for disaster area in Indonesia supported by emergency broadband access network.

    PubMed

    Sutiono, Agung Budi; Suwa, Hirohiko; Ohta, Toshizumi; Arifin, Muh Zafrullah; Kitamura, Yohei; Yoshida, Kazunari; Merdika, Daduk; Qiantori, Andri; Iskandar

    2012-12-01

    Disasters bring consequences of negative impacts on the environment and human life. One of the common cause of critical condition is traumatic brain injury (TBI), namely, epidural (EDH) and subdural hematoma (SDH), due to downfall hard things during earthquake. We proposed and analyzed the user response, namely neurosurgeon, general doctor/surgeon and nurse when they interacted with TBI computer interface. The communication systems was supported by TBI web based applications using emergency broadband access network with tethered balloon and simulated in the field trial to evaluate the coverage area. The interface consisted of demography data and multi tabs for anamnesis, treatment, follow up and teleconference interfaces. The interface allows neurosurgeon, surgeon/general doctors and nurses to entry the EDH and SDH patient's data during referring them on the emergency simulation and evaluated based on time needs and their understanding. The average time needed was obtained after simulated by Lenovo T500 notebook using mouse; 8-10 min for neurosurgeons, 12-15 min for surgeons/general doctors and 15-19 min for nurses. By using Think Pad X201 Tablet, the time needed for entry data was 5-7 min for neurosurgeon, 7-10 min for surgeons/general doctors and 12-16 min for nurses. We observed that the time difference was depending on the computer type and user literacy qualification as well as their understanding on traumatic brain injury, particularly for the nurses. In conclusion, there are five data classification for simply TBI GUI, namely, 1) demography, 2) specific anamnesis for EDH and SDH, 3) treatment action and medicine of TBI, 4) follow up data display and 5) teleneurosurgery for streaming video consultation. The type of computer, particularly tablet PC was more convenient and faster for entry data, compare to that computer mouse touched pad. Emergency broadband access network using tethered balloon is possible to be employed to cover the communications systems in

  10. Stereotactic limbic leucotomy—a follow-up study of thirty patients

    PubMed Central

    Kelly, Desmond; Mitchell-Heggs, Nita

    1973-01-01

    This prospective study reports the results of stereotactic limbic leucotomy at a mean of 17 months following surgery. Clinical improvement had occurred in twenty-four (80%) of the patients, fifteen (50%) of them being symptom free or much improved. Fourteen of sixteen patients suffering from obsessional neurosis were improved, as were five of seven with chronic anxiety and the degree of improvement at 17 months was superior to that at 6 weeks. Psychometric scores of anxiety, obsessions and neuroticism were all significantly reduced at 17 months. The mean depression scores were also significantly reduced and this result was superior to that reported in a previous study of ‘free-hand’ operations. Adverse effects were not a problem following limbic leucotomy. Emotional blunting, disinhibition, post-operative epilepsy and excessive weight gain were not encountered, and intelligence was unaffected by the operation. Limbic leucotomy is a much more limited and precise procedure than older ‘free-hand’ operations which we have studied, but its therapeutic effects are comparable and in obsessional neurosis, superior. PMID:4618906

  11. Non-paraneoplastic limbic encephalitis and central nervous HHV-6B reactivation: Causality or coincidence?

    PubMed

    Niehusmann, Pitt; Widman, Guido; Eis-Hübinger, Anna M; Greschus, Susanne; Robens, Barbara K; Grote, Alexander; Becker, Albert J

    2016-08-01

    Autoantibody-related encephalopathies represent an important differential diagnosis in adult onset epilepsy. Here, we report the case of a 25-year-old patient with new-onset epilepsy and psychotic syndrome, who underwent biopsy resection for etiological classification. MRI analysis and neuropathological examination showed a T-lymphocytic dominated encephalitis with involvement of the limbic system. An indirect immunohistochemistry approach identified autoantibodies against glutamic acid decarboxylase (GAD) in cerebral spinal fluid and serum, which were confirmed by affinity purification / mass spectrometry analysis. Further examinations revealed evidence of chromosomally integrated human herpes virus type 6B (HHV-6B). However, astrocytic expression of HHV-6 lytic protein was detected by double immunofluorescence analysis. The cerebral expression of HHV-6 antigen, a clinical improvement under antiviral therapy as well as an initial finding of HHV-6 IgM antibodies strongly argue for an additional active HHV-6B infection. Review of the literature reveals singular reports of patients with GAD antibody-positive limbic encephalitis and central nervous system infections with HHV-6B. Since herpes simplex virus encephalitis has been recently reported as a trigger of N-methyl-D-aspartate receptor antibody encephalitis, it is tempting to speculate that HHV-6B infections may trigger a non-paraneoplastic form of limbic encephalitis in a parallel cascade. PMID:27431532

  12. Continuous muscle activity, Morvan's syndrome and limbic encephalitis: ionic or non ionic disorders?

    PubMed

    Serratrice, G; Serratrice, J

    2011-06-01

    The early pathophysiologic study showed increasing evidence that autoimmunity is implicated in the pathogenesis of neuromyotonia. Antibodies to voltage gated potassium channel were detected in the serum of patients who had peripheral nerves hyperexcitability and also Morvan's disease or limbic encephalitis. These discoveries offered new approaches to treatments. Recently, antibodies previously attributed to VGKC recognise 2 surface antigens LGI1 and CASPR2 into the VGKC complex. Finally, VGKC antibodies are directed to 2 proteins the first one is a key hippocampic protein containing pre and post synaptic proteins. The second one CASPR2 is an hippocampic and paranodal protein. There clinical significance is different: hyperexcitability, limbic encephalitis without thymoma for LGI1, hyperexcitability, Morvan limbic encephalitis and frequent thymoma for CASPR2. In conclusion, the term NMT--LE--VGKC should be changed to NMT--LE with LGII and CASPR2 antibodies and classified as auto immune synaptic disorders. Mutations in genes encoding both these proteins are found in hereditary epilepsy and other syndromes. Various potassium channelopathies are closely linked to Morvan's syndromes. A new classification of antibodies will be necessary. PMID:21842591

  13. PI3 kinase is involved in cocaine behavioral sensitization and its reversal with brain area specificity

    SciTech Connect

    Zhang Xiuwu . E-mail: xwzhang@duke.edu; Mi Jing; Wetsel, William C.; Davidson, Colin; Xiong Xieying; Chen Qiang; Ellinwood, Everett H.; Lee, Tong H.

    2006-02-24

    Phosphatidylinositol 3-kinase (PI3K) is an important signaling molecule involved in cell differentiation, proliferation, survival, and phagocytosis, and may participate in various brain functions. To determine whether it is also involved in cocaine sensitization, we measured the p85{alpha}/p110 PI3K activity in the nuclear accumbens (NAc) shell, NAc core, and prefrontal cortex (PFC) following establishment of cocaine sensitization and its subsequent reversal. Naive rats were rank-ordered and split into either daily cocaine or saline pretreatment group based on their locomotor responses to an acute cocaine injection (7.5 mg/kg, i.p.). These two groups were then injected with cocaine (40 mg/kg, s.c.) or saline for 4 consecutive days followed by 9-day withdrawal. Cocaine sensitization was subsequently reversed by 5 daily injections of the D{sub 1}/D{sub 2} agonist pergolide (0.1 mg/kg, s.c.) in combination with the 5-HT{sub 3} antagonist ondansetron (0.2 mg/kg, s.c., 3.5 h after pergolide injection). After another 9-day withdrawal, behavioral cocaine sensitization and its reversal were confirmed with an acute cocaine challenge (7.5 mg/kg, i.p.), and animals were sacrificed the next day for measurement of p85{alpha}/p110 PI3K activity. Cocaine-sensitized animals exhibited increased PI3K activity in the NAc shell, and this increase was reversed by combined pergolide/ondansetron treatment, which also reversed behavioral sensitization. In the NAc core and PFC, cocaine sensitization decreased and increased the PI3K activity, respectively. These changes, in contrast to that in the NAc shell, were not normalized following the reversal of cocaine-sensitization. Interestingly, daily injections of pergolide alone in saline-pretreated animals induced PI3K changes that were similar to the cocaine sensitization-associated changes in the NAc core and PFC but not the NAc shell; furthermore, these changes in saline-pretreated animals were prevented by ondansetron given 3.5 h after

  14. Regional brain cytochrome oxidase activity in beta-amyloid precursor protein transgenic mice with the Swedish mutation.

    PubMed

    Strazielle, C; Sturchler-Pierrat, C; Staufenbiel, M; Lalonde, R

    2003-01-01

    Cytochrome oxidase activity was examined in a transgenic mouse model of Alzheimer's disease with overexpression of the 751 amino acid isoform of beta-amyloid precursor protein with the Swedish mutation under control of the murine thy-1 promoter. The neuritic plaques, abundantly localized in the hippocampus and anterior neocortical areas, showed a core devoid of enzymatic activity surrounded by higher cytochrome oxidase activity at the sites of the dystrophic neurites and activated glial cells. Quantitative measures, taken only in the healthy-appearing regional areas without neuritic plaques, were higher in numerous limbic and non-limbic regions of transgenic mice in comparison with controls. Enzymatic activity was higher in the dentate gyrus and CA2-CA3 region of the hippocampus, the anterior cingulate and primary visual cortex, two olfactory structures, the ventral part of the neostriatum, the parafascicularis nucleus of the thalamus, and the subthalamic nucleus. Brainstem regions anatomically related with altered forebrain regions were more heavily labeled as well, including the substantia nigra, the periaqueductal gray, the superior colliculus, the medial raphe, the locus coeruleus and the adjacent parabrachial nucleus, as well as the pontine nuclei, red nucleus, and trigeminal motor nucleus. Functional brain organization is discussed in the context of Alzheimer's disease. Although hypometabolism is generally observed in this pathology, the increased cytochrome oxidase activity obtained in these transgenic mice can be the result of a functional compensation on the surviving neurons, or of an early mitochondrial alteration related to increased oxidative damage. PMID:12732258

  15. Music and Emotions in the Brain: Familiarity Matters

    PubMed Central

    Pereira, Carlos Silva; Teixeira, João; Figueiredo, Patrícia; Xavier, João; Castro, São Luís; Brattico, Elvira

    2011-01-01

    The importance of music in our daily life has given rise to an increased number of studies addressing the brain regions involved in its appreciation. Some of these studies controlled only for the familiarity of the stimuli, while others relied on pleasantness ratings, and others still on musical preferences. With a listening test and a functional magnetic resonance imaging (fMRI) experiment, we wished to clarify the role of familiarity in the brain correlates of music appreciation by controlling, in the same study, for both familiarity and musical preferences. First, we conducted a listening test, in which participants rated the familiarity and liking of song excerpts from the pop/rock repertoire, allowing us to select a personalized set of stimuli per subject. Then, we used a passive listening paradigm in fMRI to study music appreciation in a naturalistic condition with increased ecological value. Brain activation data revealed that broad emotion-related limbic and paralimbic regions as well as the reward circuitry were significantly more active for familiar relative to unfamiliar music. Smaller regions in the cingulate cortex and frontal lobe, including the motor cortex and Broca's area, were found to be more active in response to liked music when compared to disliked one. Hence, familiarity seems to be a crucial factor in making the listeners emotionally engaged with music, as revealed by fMRI data. PMID:22110619

  16. Music and emotions in the brain: familiarity matters.

    PubMed

    Pereira, Carlos Silva; Teixeira, João; Figueiredo, Patrícia; Xavier, João; Castro, São Luís; Brattico, Elvira

    2011-01-01

    The importance of music in our daily life has given rise to an increased number of studies addressing the brain regions involved in its appreciation. Some of these studies controlled only for the familiarity of the stimuli, while others relied on pleasantness ratings, and others still on musical preferences. With a listening test and a functional magnetic resonance imaging (fMRI) experiment, we wished to clarify the role of familiarity in the brain correlates of music appreciation by controlling, in the same study, for both familiarity and musical preferences. First, we conducted a listening test, in which participants rated the familiarity and liking of song excerpts from the pop/rock repertoire, allowing us to select a personalized set of stimuli per subject. Then, we used a passive listening paradigm in fMRI to study music appreciation in a naturalistic condition with increased ecological value. Brain activation data revealed that broad emotion-related limbic and paralimbic regions as well as the reward circuitry were significantly more active for familiar relative to unfamiliar music. Smaller regions in the cingulate cortex and frontal lobe, including the motor cortex and Broca's area, were found to be more active in response to liked music when compared to disliked one. Hence, familiarity seems to be a crucial factor in making the listeners emotionally engaged with music, as revealed by fMRI data. PMID:22110619

  17. Brain Activity in Adolescent Major Depressive Disorder Before and After Fluoxetine Treatment

    PubMed Central

    Tao, Rongrong; Calley, Clifford S.; Hart, John; Mayes, Taryn L.; Nakonezny, Paul A.; Lu, Hanzhang; Kennard, Betsy D.; Tamminga, Carol A.; Emslie, Graham J.

    2014-01-01

    Objective Major depression in adolescents is a significant public health concern because of its frequency and severity. To examine the neurobiological basis of depression in this population, the authors studied functional activation characteristics of the brain before and after antidepressant treatment in antidepressant-naive depressed adolescents and healthy comparison subjects. Method Depressed (N=19) and healthy (N=21) adolescents, ages 11 to 18 years, underwent functional MRI assessment while viewing fearful and neutral facial expressions at baseline and again 8 weeks later. The depressed adolescents received 8 weeks of open-label fluoxetine treatment after their baseline scan. Results Voxel-wise whole brain analyses showed that depressed youths have exaggerated brain activation compared with healthy comparison subjects in multiple regions, including the frontal, temporal, and limbic cortices. The 8 weeks of fluoxetine treatment normalized most of these regions of hyperactivity in the depressed group. Region-of-interest analyses of the areas involved in emotion processing indicated that before treatment, depressed youths had significantly greater activations to fearful relative to neutral facial expressions than did healthy comparison subjects in the amygdala, orbitofrontal cortex, and subgenual anterior cingulate cortex bilaterally. Fluoxetine treatment decreased activations in all three regions, as compared with the repeat scans of healthy comparison subjects. Conclusions While effective treatments are available, the impact of depression and its treatment on the brain in adolescents is understudied. This study confirms increases in brain activation in untreated depressed adolescents and demonstrates reductions in these aberrant activations with treatment. PMID:22267183

  18. Neural activation in arousal and reward areas of the brain in day-active and night-active grass rats.

    PubMed

    Castillo-Ruiz, A; Nixon, J P; Smale, L; Nunez, A A

    2010-01-20

    In the diurnal unstriped Nile grass rat (Arvicanthis niloticus) access to a running wheel can trigger a shift in active phase preference, with some individuals becoming night-active (NA), while others continue to be day-active (DA). To investigate the contributions of different neural systems to the support of this shift in locomotor activity, we investigated the association between chronotype and Fos expression during the day and night in three major nuclei in the basal forebrain (BF) cholinergic (ACh) arousal system - medial septum (MS), vertical and horizontal diagonal band of Broca (VDB and HDB respectively) -, and whether neural activation in these areas was related to neural activity in the orexinergic system. We also measured Fos expression in dopaminergic and non-dopaminergic cells of two components of the reward system that also participate in arousal - the ventral tegmental area (VTA) and supramammillary nucleus (SUM). NAs and DAs were compared to animals with no wheels. NAs had elevated Fos expression at night in ACh cells, but only in the HDB. In the non-cholinergic cells of the BF of NAs, enhanced nocturnal Fos expression was almost universally seen, but only associated with activation of the orexinergic system for the MS/VDB region. For some of the areas and cell types of the BF, the patterns of Fos expression of DAs appeared similar to those of NAs, but were never associated with activation of the orexinergic system. Also common to DAs and NAs was a general increase in Fos expression in non-dopaminergic cells of the SUM and anterior VTA. Thus, in this diurnal species, voluntary exercise and a shift to a nocturnal chronotype changes neural activity in arousal and reward areas of the brain known to regulate a broad range of neural functions and behaviors, which may be also affected in human shift workers. PMID:19837140

  19. The sexually dimorphic nucleus of the preoptic area in the human brain: a comparative morphometric study.

    PubMed Central

    Hofman, M A; Swaab, D F

    1989-01-01

    The sexually dimorphic nucleus of the preoptic area (SDN-POA) in the human hypothalamus is an ovoid, densely packed collection of large cells. The size, shape and cellular morphology of the SDN-POA was examined in relation to sex and age in adult human subjects. In this region the following parameters were measured: length of the rostrocaudal axis, maximum cross-sectional area, volume, numerical cell density, total number of cells, and the diameter of the cell nucleus. The SDN-POA was elongated in females and more spherical in males. The mean volume and total cell number were markedly sexually dimorphic: the volume of the SDN-POA was 2.2 times as large in males as in females and contained 2.1 times as many cells. No sex differences were observed in either cell density or mean diameter of the cell nuclei. Furthermore, multivariate regression analysis revealed that there are also sex-linked differences in the structural organisation of the human SDN-POA, finding expression in the way the morphometric parameters are interrelated. Of the parameters measured, only the volume and cell number of the SDN-POA showed a dramatic decrease with ageing. The reduction in cell number, however, was not constant throughout adulthood but was found to depend upon sex and age. In males, a major reduction in SDN-POA cell number was observed between the age of 50-60 years. In females, cell death was found to be more prominent than in males, especially among old people (t greater than 70 years), dropping to values which were only 10-15% of the cell number found in early childhood. In conclusion, the human SDN-POA has a sex-dependent pattern of ageing. Finally, the morphology of the SDN-POA was compared with that of other hypothalamic regions--the suprachiasmatic nucleus (SCN) and the paraventricular nucleus (PVN)--both in man and in rat. Species-specific differences in the dimensions of these nuclear regions are discussed in the light of their assumed functional significance. PMID:2606795

  20. Dosha brain-types: A neural model of individual differences.

    PubMed

    Travis, Frederick T; Wallace, Robert Keith

    2015-01-01

    This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations. PMID:26834428

  1. Dosha brain-types: A neural model of individual differences

    PubMed Central

    Travis, Frederick T.; Wallace, Robert Keith

    2015-01-01

    This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations. PMID:26834428

  2. Hypersexuality or altered sexual preference following brain injury.

    PubMed Central

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

    1986-01-01

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

  3. In psychopathic patients emotion attribution modulates activity in outcome-related brain areas.

    PubMed

    Sommer, Monika; Sodian, Beate; Döhnel, Katrin; Schwerdtner, Johannes; Meinhardt, Jörg; Hajak, Göran

    2010-05-30

    The understanding that other people's emotional states depend on the fulfilment of their intention is fundamentally important for responding adequately to others. Psychopathic patients show severe deficits in responding adequately to other people's emotion. The present study explored whether these impairments are associated with deficits in the ability to infer others' emotional states. Using functional magnetic resonance imaging (fMRI), identical cartoon stories, depicting a subject whose intention was fulfilled or not fulfilled, were presented to 14 psychopathic patients and 14 non-psychopathic patients. The participants should indicate the protagonist's emotional state. Additionally, a non-mentalizing control condition was presented. The two groups showed no behavioural differences. But in non-psychopathic patients emotion attribution was associated with increased activity of the mirror neuron system, the bilateral supramarginal gyrus and the superior frontal gyrus. In contrast psychopathic patients showed increased activation of regions associated with outcome monitoring and attention, such as the orbitofrontal cortex, the medial frontal cortex and temporo-parietal areas. The results emphasize that although psychopathic patients show no deficits in reasoning about other people's emotion if an explicit evaluation is demanded, they use divergent neural processing strategies that are related to more rational, outcome-oriented processes. PMID:20417065

  4. Comparative effects of dydrogesterone and medroxyprogesterone acetate in critical areas: the brain and the vessels.

    PubMed

    Simoncini, Tommaso; Mannella, Paolo; Pluchino, Nicola; Genazzani, Andrea R

    2007-10-01

    Several epidemiological and observational studies have investigated the role of hormone replacement therapy (HRT) in postmenopausal women. Within a few years, clinicians shifted from considering HRT as the panacea for everything to considering it a venomous poison with which women, in search of the fountain of eternal youth, could instead harm themselves. This debate is not yet settled and the unexplained discrepancy between basic science and some of the clinical trials has fueled the discussion. One of the hottest areas of discussion remains the role of progestins. For many years, progestins were considered only as necessary additions to estrogen to protect the endometrium. However, we now know that every progestin has its own specific activities on different tissues, which can vary significantly between progestins of different classes and even within the same class. Indeed, different progestins may support or oppose the effects of estrogen depending on the tissue, thereby supporting the concept that the clinical selection of progestins for HRT is critical in determining potential positive or detrimental effects. Newer progestins, such as dydrogesterone, show effects that are remarkably different from those of other agents; these actions might be particularly relevant in the central nervous system and the cardiovascular system. The aim of the present paper is to review the comparative effects of dydrogesterone and other progestins at these sites, supporting the idea that the progestin has to be clinically selected. PMID:17943534

  5. The Brain Activity in Brodmann Area 17: A Potential Bio-Marker to Predict Patient Responses to Antiepileptic Drugs

    PubMed Central

    Xu, Xin; Fang, Weidong; Zeng, Kebin; Yang, Mingming; Li, Chenyu; Wang, Shasha; Li, Minghui; Wang, Xuefeng

    2015-01-01

    In this study, we aimed to predict newly diagnosed patient responses to antiepileptic drugs (AEDs) using resting-state functional magnetic resonance imaging tools to explore changes in spontaneous brain activity. We recruited 21 newly diagnosed epileptic patients, 8 drug-resistant (DR) patients, 11 well-healed (WH) patients, and 13 healthy controls. After a 12-month follow-up, 11 newly diagnosed epileptic patients who showed a poor response to AEDs were placed into the seizures uncontrolled (SUC) group, while 10 patients were enrolled in the seizure-controlled (SC) group. By calculating the amplitude of fractional low-frequency fluctuations (fALFF) of blood oxygen level-dependent signals to measure brain activity during rest, we found that the SUC patients showed increased activity in the bilateral occipital lobe, particularly in the cuneus and lingual gyrus compared with the SC group and healthy controls. Interestingly, DR patients also showed increased activity in the identical cuneus and lingual gyrus regions, which comprise Brodmann’s area 17 (BA17), compared with the SUC patients; however, these abnormalities were not observed in SC and WH patients. The receiver operating characteristic (ROC) curves indicated that the fALFF value of BA17 could differentiate SUC patients from SC patients and healthy controls with sufficient sensitivity and specificity prior to the administration of medication. Functional connectivity analysis was subsequently performed to evaluate the difference in connectivity between BA17 and other brain regions in the SUC, SC and control groups. Regions nearby the cuneus and lingual gyrus were found positive connectivity increased changes or positive connectivity changes with BA17 in the SUC patients, while remarkably negative connectivity increased changes or positive connectivity decreased changes were found in the SC patients. Additionally, default mode network (DMN) regions showed negative connectivity increased changes or negative

  6. Single housing during early adolescence causes time-, area- and peptide-specific alterations in endogenous opioids of rat brain

    PubMed Central

    Granholm, L; Roman, E; Nylander, I

    2015-01-01

    BACKGROUND AND PURPOSE A number of experimental procedures require single housing to assess individual behaviour and physiological responses to pharmacological treatments. The endogenous opioids are closely linked to social interaction, especially early in life, and disturbance in the social environment may affect opioid peptides and thereby confound experimental outcome. The aim of the present study was to examine time-dependent effects of single housing on opioid peptides in rats. EXPERIMENTAL APPROACH Early adolescent Sprague Dawley rats (post-natal day 22) were subjected to either prolonged (7 days) or short (30 min) single housing. Several brain regions were dissected and immunoreactive levels of Met-enkephalin-Arg6Phe7 (MEAP), dynorphin B and nociception/orphanin FQ, as well as serum corticosterone were measured using RIA. KEY RESULTS Prolonged single housing reduced immunoreactive MEAP in hypothalamus, cortical regions, amygdala, substantia nigra and periaqueductal grey. Short single housing resulted in an acute stress response as indicated by high levels of corticosterone, accompanied by elevated immunoreactive nociceptin/orphanin FQ in medial prefrontal cortex, nucleus accumbens and amygdala. Neither short nor prolonged single housing affected dynorphin B. CONCLUSIONS AND IMPLICATIONS Disruption in social environmental conditions of rats, through single housing during early adolescence, resulted in time-, area- and peptide-specific alterations in endogenous opioids in the brain. These results provide further evidence for an association between early life social environment and opioids. Furthermore, the results have implications for experimental design; in any pharmacological study involving opioid peptides, it is important to distinguish between effects induced by housing and treatment. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http

  7. Correlation between the Effects of Acupuncture at Taichong (LR3) and Functional Brain Areas: A Resting-State Functional Magnetic Resonance Imaging Study Using True versus Sham Acupuncture.

    PubMed

    Wu, Chunxiao; Qu, Shanshan; Zhang, Jiping; Chen, Junqi; Zhang, Shaoqun; Li, Zhipeng; Chen, Jiarong; Ouyang, Huailiang; Huang, Yong; Tang, Chunzhi

    2014-01-01

    Functional magnetic resonance imaging (fMRI) has been shown to detect the specificity of acupuncture points, as proved by numerous studies. In this study, resting-state fMRI was used to observe brain areas activated by acupuncture at the Taichong (LR3) acupoint. A total of 15 healthy subjects received brain resting-state fMRI before acupuncture and after sham and true acupuncture, respectively, at LR3. Image data processing was performed using Data Processing Assistant for Resting-State fMRI and REST software. The combination of amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) was used to analyze the changes in brain function during sham and true acupuncture. Acupuncture at LR3 can specifically activate or deactivate brain areas related to vision, movement, sensation, emotion, and analgesia. The specific alterations in the anterior cingulate gyrus, thalamus, and cerebellar posterior lobe have a crucial effect and provide a valuable reference. Sham acupuncture has a certain effect on psychological processes and does not affect brain areas related to function. PMID:24963329

  8. Gender differences in working memory networks: A BrainMap meta-analysis

    PubMed Central

    Hill, Ashley C.; Laird, Angela R.; Robinson, Jennifer L.

    2014-01-01

    Gender differences in psychological processes have been of great interest in a variety of fields. While the majority of research in this area has focused on specific differences in relation to test performance, this study sought to determine the underlying neurofunctional differences observed during working memory, a pivotal cognitive process shown to be predictive of academic achievement and intelligence. Using the BrainMap database, we performed a meta-analysis and applied activation likelihood estimation to our search set. Our results demonstrate consistent working memory networks across genders, but also provide evidence for gender-specific networks whereby females consistently activate more limbic (e.g., amygdala and hippocampus) and prefrontal structures (e.g., right inferior frontal gyrus), and males activate a distributed network inclusive of more parietal regions. These data provide a framework for future investigation using functional or effective connectivity methods to elucidate the underpinnings of gender differences in neural network recruitment during working memory tasks. PMID:25042764

  9. Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors.

    PubMed

    Neumann, Inga D; Landgraf, Rainer

    2012-11-01

    Oxytocin and vasopressin are regulators of anxiety, stress-coping, and sociality. They are released within hypothalamic and limbic areas from dendrites, axons, and perikarya independently of, or coordinated with, secretion from neurohypophysial terminals. Central oxytocin exerts anxiolytic and antidepressive effects, whereas vasopressin tends to show anxiogenic and depressive actions. Evidence from pharmacological and genetic association studies confirms their involvement in individual variation of emotional traits extending to psychopathology. Based on their opposing effects on emotional behaviors, we propose that a balanced activity of both brain neuropeptide systems is important for appropriate emotional behaviors. Shifting the balance between the neuropeptide systems towards oxytocin, by positive social stimuli and/or psychopharmacotherapy, may help to improve emotional behaviors and reinstate mental health. PMID:22974560

  10. Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning.

    PubMed

    Linnman, Clas; Zeidan, Mohamed A; Pitman, Roger K; Milad, Mohammed R

    2012-02-01

    We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differentially conditioned skin conductance responses. Midbrain and insula resting metabolism negatively predicted midbrain and insula functional reactivity, while dorsal anterior cingulate resting metabolism positively predicted midbrain functional reactivity. We conclude that resting metabolism in limbic areas can predict some aspects of psychophysiological and neuronal reactivity during fear learning. PMID:22207247

  11. Resting cerebral metabolism correlates with skin conductance and functional brain activation during fear conditioning

    PubMed Central

    Linnman, Clas; Zeidan, Mohamed A.; Pitman, Roger K; Milad, Mohammed R.

    2011-01-01

    We investigated whether resting brain metabolism can be used to predict autonomic and neuronal responses during fear conditioning in 20 healthy humans. Regional cerebral metabolic rate for glucose was measured via positron emission tomography at rest. During conditioning, autonomic responses were measured via skin conductance, and blood oxygen level dependent signal was measured via functional magnetic resonance imaging. Resting dorsal anterior cingulate metabolism positively predicted differentially conditioned skin conductance responses. Midbrain and insula resting metabolism negatively predicted midbrain and insula functional reactivity, while dorsal anterior cingulate resting metabolism positively predicted midbrain functional reactivity. We conclude that resting metabolism in limbic areas can predict some aspects of psychophysiological and neuronal reactivity during fear learning. PMID:22207247

  12. Directed Evolution of a Novel Adeno-associated Virus (AAV) Vector That Crosses the Seizure-compromised Blood–Brain Barrier (BBB)

    PubMed Central

    Gray, Steven J; Blake, Bonita L; Criswell, Hugh E; Nicolson, Sarah C; Samulski, R Jude; McCown, Thomas J

    2009-01-01

    DNA shuffling and directed evolution were employed to develop a novel adeno-associated virus (AAV) vector capable of crossing the seizure-compromised blood–brain barrier (BBB) and transducing cells in the brain. Capsid DNA from AAV serotypes 1–6, 8, and 9 were shuffled and recombined to create a library of chimeric AAVs. One day after kainic acid–induced limbic seizure activity in rats, the virus library was infused intravenously (i.v.), and 3 days later, neuron-rich cells were mechanically dissociated from seizure-sensitive brain sites, collected and viral DNA extracted. After three cycles of selection, green fluorescent protein (GFP)–packaged clones were administered directly into brain or i.v. 1 day after kainic acid–induced seizures. Several clones that were effective after intracranial administration did not transduce brain cells after the i.v. administration. However, two clones (32 and 83) transduced the cells after direct brain infusion and after i.v. administration transduced the cells that were localized to the piriform cortex and ventral hippocampus, areas exhibiting a seizure-compromised BBB. No transduction occurred in areas devoid of BBB compromise. Only one parental serotype (AAV8) exhibited a similar expression profile, but the biodistribution of 32 and 83 diverged dramatically from this parental serotype. Thus, novel AAV vectors have been created that can selectively cross the seizure-compromised BBB and transduce cells. PMID:20040913

  13. Dynamic regional phase synchrony (DRePS): An Instantaneous Measure of Local fMRI Connectivity Within Spatially Clustered Brain Areas.

    PubMed

    Omidvarnia, Amir; Pedersen, Mangor; Walz, Jennifer M; Vaughan, David N; Abbott, David F; Jackson, Graeme D

    2016-05-01

    Dynamic functional brain connectivity analysis is a fast expanding field in computational neuroscience research with the promise of elucidating brain network interactions. Sliding temporal window based approaches are commonly used in order to explore dynamic behavior of brain networks in task-free functional magnetic resonance imaging (fMRI) data. However, the low effective temporal resolution of sliding window methods fail to capture the full dynamics of brain activity at each time point. These also require subjective decisions regarding window size and window overlap. In this study, we introduce dynamic regional phase synchrony (DRePS), a novel analysis approach that measures mean local instantaneous phase coherence within adjacent fMRI voxels. We evaluate the DRePS framework on simulated data showing that the proposed measure is able to estimate synchrony at higher temporal resolution than sliding windows of local connectivity. We applied DRePS analysis to task-free fMRI data of 20 control subjects, revealing ultra-slow dynamics of local connectivity in different brain areas. Spatial clustering based on the DRePS feature time series reveals biologically congruent local phase synchrony networks (LPSNs). Taken together, our results demonstrate three main findings. Firstly, DRePS has increased temporal sensitivity compared to sliding window correlation analysis in capturing locally synchronous events. Secondly, DRePS of task-free fMRI reveals ultra-slow fluctuations of ∼0.002-0.02 Hz. Lastly, LPSNs provide plausible spatial information about time-varying brain local phase synchrony. With the DRePS method, we introduce a framework for interrogating brain local connectivity, which can potentially provide biomarkers of human brain function in health and disease. Hum Brain Mapp 37:1970-1985, 2016. © 2016 Wiley Periodicals, Inc. PMID:27019380

  14. Projections from the parabrachial nucleus to the vestibular nuclei: potential substrates for autonomic and limbic influences on vestibular responses.

    PubMed

    Balaban, Carey D

    2004-01-16

    Previous anatomical studies in rabbits and rats have shown that the superior vestibular nucleus (SVN), medial vestibular nucleus (MVN) and inferior vestibular nucleus (IVN) project to the parabrachial nucleus (PBN) and Kölliker-Fuse (KF) nucleus. Adult male albino rabbits and Long-Evans rats received iontophoretic injections of biotinylated dextran amine, Phaseolus vulgaris leucoagglutinin, Fluoro-Gold or tetramethylrhodamine dextran amine into either the vestibular nuclei or the PBN and KF nuclei. The results were similar in both rats and rabbits. Injections of retrograde tracers into the vestibular nuclei produced retrogradely labeled neurons bilaterally in caudal third of the medial, external medial, and external lateral PBN in both species, with more variable labeling in KF. Rats also had consistent bilateral (predominantly contralateral) labeling in the ventrolateral PBN. The most prominent labeling was produced from injections that included the SVN, with fewer labeled neurons observed from injections in the caudal MVN and the IVN. Anterograde transport of BDA from injections into the PBN and KF nuclei of rabbits revealed prominent projections to the SVN, dorsal aspect of the rostral MVN, caudal MVN, pars beta of the LVN and IVN. These connections appear to contain a component that is reciprocal to the vestibulo-parabrachial pathway and a non-reciprocal component to regions connected with the vestibulocerebellum and vestibulo-motor reflex pathways. These connections support the concept that a synthesis of autonomic, vestibular and limbic information is an integral property of pathways related to balance control in both the brain stem and forebrain. It is suggested that these projections may contribute broadly to both performance tradeoffs in vestibular-related pathways during variations in the behavioral context and affective state and the close association between anxiety and balance function. PMID:14670639

  15. A new look at borderline personality disorder and related disorders: hyper-reactivity in the limbic system and lower centers.

    PubMed

    Stone, Michael H

    2013-01-01

    Borderline Personality Disorder (BPD) has been often described recently as a condition characterized by emotional dysregulation. Several other conditions share this attribute; namely, Bipolar Disorder (BD), Attention-Deficit/Hyperactivity Disorder (ADHD), Intermittent Explosive Disorder (IED), and Major Depressive Disorder (MDD). The dysregulation is not always in the same direction: BPD, BD, ADHD, and IED, for example, show over-reactivity or "hyperactivity" of emotional responses, whereas patients with MDD show emotional sluggishness and underactivity. At the clinical/descriptive level the "over-reactive" conditions appear separate and distinct. BPD constitutes a large domain within the psychopathological arena, appearing to contain within it a variety of etiologically diverse subtypes. Among the latter is a type of BPD linked closely with Bipolar Disorder; family studies of either condition show an overrepresentation of both: BPD patients with bipolar relatives; Bipolar patients with BPD relatives. A significant percentage of children with ADHD go on to develop either BPD or BD as they approach adulthood. If one shifts the spotlight to neurophysiology, as captured by MRI studies, however, it emerges that an important subtype of BPD, and also BD, ADHD, and IED-share common features of abnormalities and peculiarities in the limbic system and in the cortex, especially the prefrontal cortex. Deeper subcortical regions such as the periaqueductal gray may also be implicated in strong emotional reactions. The diversity of clinical "over-reactive" conditions appear to harken back to a kind of unity at the brain-change level. There are therapeutic implications here, such as the advisability of mood stabilizers in many cases of BPD, not just for Bipolar Disorder. PMID:24001165

  16. The associative and limbic thalamus in the pathophysiology of obsessive-compulsive disorder: an experimental study in the monkey.

    PubMed

    Rotge, J Y; Aouizerate, B; Amestoy, V; Lambrecq, V; Langbour, N; Nguyen, T H; Dovero, S; Cardoit, L; Tignol, J; Bioulac, B; Burbaud, P; Guehl, D

    2012-01-01

    Obsessive-compulsive disorder (OCD) is a frequent psychiatric disorder characterized by repetitive intrusive thoughts and severe anxiety, leading to compulsive behaviors. Although medical treatment is effective in most cases, resistance is observed in about 30% of patients. In this context, deep brain stimulation (DBS) of the caudate or subthalamic nuclei has been recently proposed with encouraging results. However, some patients were unimproved or exhibited awkward side effects. Therefore, exploration of new targets for DBS remains critical in OCD. In the latter, functional imaging studies revealed overactivity in the limbic and associative cortico-subcortical loops encompassing the thalamus. However, the role of the thalamus in the genesis of repetitive behaviors and related anxiety is unknown. Here, we tested the hypothesis that pharmacological-induced overactivity of the medial thalamus could give rise to abnormal behaviors close to that observed in OCD. We modulated the ventral anterior (VA) and medial dorsal (MD) nuclei activity by in situ bicuculline (GABA(A) antagonist) microinjections in subhuman primates and assessed their pharmacological-induced behavior. Bicuculline injections within the VA caused significant repetitive and time-consuming motor acts whereas those performed within the MD induced symptoms of dysautonomic dysregulation along with abnormal vocalizations and marked motor hypoactivity. These findings suggest that overactivation of the VA and MD nuclei of the thalamus provokes compulsive-like behaviors and neurovegetative manifestations usually associated with the feeling of anxiety in OCD patients. In further research, this translational approach should allow us to test the effectiveness and side effects of these thalamic nuclei DBS in monkey and perhaps, in a second step, to propose a transfer of this technique to severely disabled OCD patients. PMID:23010765

  17. Brain Mechanisms Supporting Modulation of Pain by Mindfulness Meditation

    PubMed Central

    Zeidan, F.; Martucci, K.T.; Kraft, R.A.; Gordon, N.S.; McHaffie, J.G.; Coghill, R.C.

    2011-01-01

    The subjective experience of one’s environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a non-evaluative representation of sensory events. To better understand how meditation influences the sensory experience, we employed arterial spin labeling (ASL) functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After four-days of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain-unpleasantness by 57% and pain-intensity ratings by 40% when compared to rest. A two factor repeated measures analysis of variance was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contra lateral primary somatosensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent in put and executive-order brain areas. Taken together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information. PMID:21471390

  18. Metastatic brain tumor

    MedlinePlus

    Brain tumor - metastatic (secondary); Cancer - brain tumor (metastatic) ... For many people with metastatic brain tumors, the cancer is not curable. It will eventually spread to other areas of the body. Prognosis depends on the type of tumor ...

  19. Partial kindling of the ventral hippocampus: identification of changes in limbic physiology which accompany changes in feline aggression and defense.

    PubMed

    Adamec, R E

    1991-03-01

    This study examined the interictal consequences of partial kindling of the ventral perforant path on attack and defensive behavior in the domestic cat. Partial kindling produced a lasting increase in defense response of cats to both rats and conspecific threat howls. In addition, there was a lasting suppression of approach-attack behaviors directed toward rats. The suppression of some components of approach-attack were shown to be independent of the increases in defensive response. The effects of partial kindling of the ventral perforant path on spread of seizure activity into the amygdala, and on the output of the amygdala to both the ventromedial hypothalamus (VMH) and bed nucleus of the stria terminalis (BNST) were also examined. In addition, the effects of repeated hippocampal seizures on recurrent inhibition in the trisynaptic circuit (areas CA1 and CA3) were investigated. Growth of seizure activity in the amygdala and VMH as partial kindling progressed was essential for behavioral change. In addition, interictal long-term potentiation of potentials evoked in the VMH and in the BNST by pulsed stimulation of the amygdala followed partial kindling or afterdischarge threshold determination in the ventral perforant path. A lasting interictal increase in inhibition in area CA3 and a lasting interictal failure of inhibition in area CA1 of the ventral hippocampus also followed partial kindling. These changes in limbic physiology were related to the behavioral changes produced by partial kindling. The analysis revealed the importance of the amygdalo-VMH pathway in increased defensive response to rats. The amygdalo-BNST pathway is not important in mediating defensive response to prey, but it is implicated in suppression of some types of predatory aggression. Finally, changes in neural inhibition in the ventral hippocampus in areas CA1 and CA3 are associated with changes in both defensiveness and predatory aggression. PMID:1648239

  20. A study of parabens and bisphenol A in surface water and fish brain tissue from the Greater Pittsburgh Area.

    PubMed

    Renz, Lara; Volz, Conrad; Michanowicz, Drew; Ferrar, Kyle; Christian, Charles; Lenzner, Diana; El-Hefnawy, Talal

    2013-05-01

    Pollution from xenoestrogens has been discovered in the aquatic environment of the Greater Pittsburgh Area and is suspected to be caused by the failing sewer system. Personal care products and plasticizers have the potential to enter the water supply though treated and untreated sewage. Many of these compounds are suspected xenoestrogens. Paraben detection in surface waters was as follows: methyl paraben ranged between 2.2 to 17.3 ppt; ethyl paraben was not detectable; propyl paraben was detected at 9.2 and 12.0 ppt; butyl paraben was detected at 0.2 ppt. BPA was detected between 0.6 and 15.4 ppt. Estrogenic potential of extracts from fish brain tissue was tested via Bromodeoxyuridine MCF-7 analysis and paired with HPLC-MS to investigate the presence of xenoestrogens. All samples were non-detectable for parabens. BPA was detected in 44 of the 58 samples, with a range from non-detectable to 120 pg/g. BCFs were calculated. Results were statistically significant for location of capture (p < 0.05) and correlation existed between estrogenicity and BPA. PMID:23479059

  1. Intrathecal immunoglobulin A and G antibodies to synapsin in a patient with limbic encephalitis

    PubMed Central

    Piepgras, Johannes; Höltje, Markus; Otto, Carolin; Harms, Hendrik; Satapathy, Annyesha; Cesca, Fabrizia; Benfenati, Fabio; Gitler, Daniel; Pich, Andreas; Zander, Johannes-Friedrich

    2015-01-01

    Objective: To report on the identification of intrathecally synthesized immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies to synapsin, a synaptic vesicle-associated protein, in a patient with limbic encephalitis. Methods: Methods included clinical characterization, indirect immunofluorescence, immunoprecipitation, mass spectrometry, immunoblots of wild-type and synapsin I/II/III knockout mice, and cell-based assays with synapsin Ia, Ib, IIa, and IIb plasmids. Results: A 69-year-old man presented with confusion, disorientation, seizures, and left hippocampal hyperintensities on MRI. CSF examinations revealed an intrathecal IgA and IgG synthesis. Except for IgG antibodies to voltage-gated potassium channels in CSF, screening for known neuronal autoantibodies in serum and CSF was negative. However, indirect immunofluorescence using the patient's CSF showed binding of IgA to mouse hippocampus, amygdala, and cerebellum. Immunoprecipitation with CSF IgA followed by mass spectrometry identified synapsin as autoantigenic target. Knockout tissues and cell-based assays confirmed that IgA and IgG in the patient's CSF and serum reacted with synapsin Ia, Ib, and IIa. Calculation of antibody indices proved intrathecal synthesis of anti-synapsin IgA and IgG. The patient responded clinically to immunotherapy but developed left hippocampal atrophy. CSF IgA or IgG of the patient did not bind to live, unfixed, and nonpermeabilized mouse hippocampal neurons, compatible with synapsin being an intracellular antigen. Conclusions: This report identifies isoforms of the synaptic vesicle-associated protein synapsin as targets of intrathecally produced IgA and IgG antibodies in a patient with limbic encephalitis. Future studies should clarify the prevalence and pathogenic relevance of anti-synapsin antibodies in limbic encephalitis. PMID:26587554

  2. Dissection of the hippocampus proper and the associated structures in preserved horse brains.

    PubMed

    Cope, Lee Anne

    2010-01-01

    The limbic system is a complicated region of the brain to teach in an undergraduate neuroanatomy course. The students often struggled with the complexity and interconnection of the structures of this system to other cortical regions. The following is a description of two dissections that used preserved horse brains to help students visualize the major components of this system and also comprehend the topographic organization of some of these structures to other regions or structures of the brain. PMID:23494866

  3. Renal Cell Carcinoma Presenting with Paraneoplastic Hallucinations and Cognitive Decline from Limbic Encephalitis.

    PubMed

    Harrison, Joshua W; Cherukuri, Ramesh; Buchan, Debra

    2015-07-01

    We present a 66-year-old woman with 2 months of visual hallucinations, unintentional weight loss, and short-term memory decline, whose clinical presentation and EEG supported a diagnosis of limbic encephalitis. Subsequent evaluation for a paraneoplastic etiology revealed a renal mass, which was resected and identified as clear cell renal carcinoma. The patient's clinical condition improved after resection of the mass. When patients present with incongruous subacute neuropsychiatric symptoms, clinicians should be mindful of paraneoplastic neurological disorders, as early diagnosis and treatment of malignancy may lead to symptomatic improvement. PMID:25608740

  4. Disrupted functional brain connectome in unilateral sudden sensorineural hearing loss.

    PubMed

    Xu, Haibo; Fan, Wenliang; Zhao, Xueyan; Li, Jing; Zhang, Wenjuan; Lei, Ping; Liu, Yuan; Wang, Haha; Cheng, Huamao; Shi, Hong

    2016-05-01

    Sudden sensorineural hearing loss (SSNHL) is generally defined as sensorineural hearing loss of 30 dB or greater over at least three contiguous audiometric frequencies and within a three-day period. This hearing loss is usually unilateral and can be associated with tinnitus and vertigo. The pathogenesis of unilateral sudden sensorineural hearing loss is still unknown, and the alterations in the functional connectivity are suspected to involve one possible pathogenesis. Despite scarce findings with respect to alterations in brain functional networks in unilateral sudden sensorineural hearing loss, the alterations of the whole brain functional connectome and whether these alterations were already in existence in the acute period remains unknown. The aim of this study was to investigate the alterations of brain functional connectome in two large samples of unilateral sudden sensorineural hearing loss patients and to investigate the correlation between unilateral sudden sensorineural hearing loss characteristics and changes in the functional network properties. Pure tone audiometry was performed to assess hearing ability. Abnormal changes in the peripheral auditory system were examined using conventional magnetic resonance imaging. The graph theoretical network analysis method was used to detect brain connectome alterations in unilateral sudden sensorineural hearing loss. Compared with the control groups, both groups of unilateral SSNHL patients exhibited a significantly increased clustering coefficient, global efficiency, and local efficiency but a significantly decreased characteristic path length. In addition, the primary increased nodal strength (e.g., nodal betweenness, hubs) was observed in several regions primarily, including the limbic and paralimbic systems, and in the auditory network brain areas. These findings suggest that the alteration of network organization already exists in unilateral sudden sensorineural hearing loss patients within the acute period

  5. Does excessive play of violent first-person-shooter-video-games dampen brain activity in response to emotional stimuli?

    PubMed

    Montag, Christian; Weber, Bernd; Trautner, Peter; Newport, Beate; Markett, Sebastian; Walter, Nora T; Felten, Andrea; Reuter, Martin

    2012-01-01

    The present case-control study investigated the processing of emotional pictures in excessive first-person-shooter-video-players and control persons. All participants of the fMRI experiment were confronted with pictures from four categories including pleasant, unpleasant, neutral content and pictures from the first-person-shooter-video-game 'Counterstrike'. Compared to controls, gamers showed a significantly lower activation of the left lateral medial frontal lobe while processing negative emotions. Another interesting finding of the study represents the higher activation of frontal and temporal brain areas in gamers when processing screen-shots from the first-person-shooter-video-game 'Counterstrike'. Higher brain activity in the lateral prefrontal cortex could represent a protection mechanism against experiencing negative emotions by down-regulating limbic brain activity. Due to a frequent confrontation with violent scenes, the first-person-shooter-video-gamers might have habituated to the effects of unpleasant stimuli resulting in lower brain activation. Individual differences in brain activations of the contrast Counterstrike>neutral pictures potentially resemble the activation of action-scripts related to the video-game. PMID:21982747

  6. A comparison of heritability maps of cortical surface area and thickness and the influence of adjustment for whole brain measures: a magnetic resonance imaging twin study.

    PubMed

    Eyler, Lisa T; Chen, Chi-Hua; Panizzon, Matthew S; Fennema-Notestine, Christine; Neale, Michael C; Jak, Amy; Jernigan, Terry L; Fischl, Bruce; Franz, Carol E; Lyons, Michael J; Grant, Michael; Prom-Wormley, Elizabeth; Seidman, Larry J; Tsuang, Ming T; Fiecas, Mark Joseph A; Dale, Anders M; Kremen, William S

    2012-06-01

    Understanding the genetic and environmental contributions to measures of brain structure such as surface area and cortical thickness is important for a better understanding of the nature of brain-behavior relationships and changes due to development or disease. Continuous spatial maps of genetic influences on these structural features can contribute to our understanding of regional patterns of heritability, since it remains to be seen whether genetic contributions to brain structure respect the boundaries of any traditional parcellation approaches. Using data from magnetic resonance imaging scans collected on a large sample of monozygotic and dizygotic twins in the Vietnam Era Twin Study of Aging, we created maps of the heritability of areal expansion (a vertex-based area measure) and cortical thickness and examined the degree to which these maps were affected by adjustment for total surface area and mean cortical thickness. We also compared the approach of estimating regional heritability based on the average heritability of vertices within the region to the more traditional region-of-interest (ROI)-based approach. The results suggested high heritability across the cortex for areal expansion and, to a slightly lesser degree, for cortical thickness. There was a great deal of genetic overlap between global and regional measures for surface area, so maps of region-specific genetic influences on surface area revealed more modest heritabilities. There was greater inter-regional variability in heritabilities when calculated using the traditional ROI-based approach compared to summarizing vertex-by-vertex heritabilities within regions. Discrepancies between the approaches were greatest in small regions and tended to be larger for surface area than for cortical thickness measures. Implications regarding brain phenotypes for future genetic association studies are discussed. PMID:22856366

  7. Improvement of paraneoplastic limbic encephalitis after systemic treatment with rituximab in a patient with B-cell chronic lymphocytic leukemia.

    PubMed

    Nogai, Hendrik; Israel-Willner, Heike; Zschenderlein, Rolf; Pezzutto, Antonio

    2013-01-01

    Limbic encephalitis is an inflammatory disease of the central nervous system characterized by diverse neurologic symptoms including mnestic disturbances, hallucinations, and seizures as well as behavioral symptoms like depression, personality changes, and acute confusional states resembling dementia. Several antibodies have been described in the pathogenesis of limbic encephalitis. It is often a paraneoplastic syndrome associated with small cell lung cancer, breast cancer, or Hodgkin's lymphoma among others. Here, we report a patient with B-cell chronic lymphocytic leukemia (B-CLL), presenting with otherwise unexplained neurologic symptoms consistent with limbic encephalitis. Despite intensive diagnostic procedures, no causing agent could be identified. Pleocytosis consisting of T cells was detected in the cerebrospinal fluid (CSF). We initiated anti-B-cell therapy with Rituximab for B-CLL with quick and durable resolution of symptoms. We speculate that disruption of interaction between autoreactive T and malignant B cells is responsible for the therapeutic effect of Rituximab. PMID:23984126

  8. Striatal-limbic activation is associated with intensity of anticipatory anxiety.

    PubMed

    Yang, Hongyu; Spence, Jeffrey S; Devous, Michael D; Briggs, Richard W; Goyal, Aman; Xiao, Hong; Yadav, Hardik; Adinoff, Bryon

    2012-11-30

    Anxiety experienced in anticipation of impending aversive events induces striatal-limbic activation. However, previous functional magnetic imaging (fMRI) studies of anticipatory anxiety have utilized post-test measures of anxiety, making a direct association between neural activation and distress problematic. This paradigm was designed to assess the blood-oxygen-level-dependent (BOLD) response to an aversive conditioned stimulus while simultaneously measuring subjective anxiety. Fifteen male healthy subjects (45.5±8.5 years old) were studied. A high-threat conditioned stimulus (CS) was paired with either an unpredictable, highly aversive (painful) or non-aversive (non-painful) unconditioned stimulus and compared to a low-threat CS paired with a predictable, non-aversive stimulus. Neural response was assessed with fMRI, and subjective anxiety (1-4) was recorded upon the presentation of each CS. High subjective ratings of real-time anticipatory anxiety (2-4), relative to low anticipatory anxiety (1), elicited increased activation in the bilateral striatum, bilateral orbital frontal cortex, left anterior insula, and anterior cingulate cortex (ACC) and decreased activation in the posterior cingulate cortex (PCC). The amplitude of BOLD signal change generally paralleled the subjective rating of anxiety. Real-time measures of anticipatory anxiety confirm previous reports, using post-test measures of anxiety, of striatal-limbic activation during anticipatory anxiety while simultaneously demonstrating an increase in BOLD response in parallel with heightened anxiety. PMID:23137803

  9. Successful antidepressant chronotherapeutics enhance fronto-limbic neural responses and connectivity in bipolar depression.

    PubMed

    Vai, Benedetta; Poletti, Sara; Radaelli, Daniele; Dallaspezia, Sara; Bulgarelli, Chiara; Locatelli, Clara; Bollettini, Irene; Falini, Andrea; Colombo, Cristina; Smeraldi, Enrico; Benedetti, Francesco

    2015-08-30

    The identification of antidepressant response predictors in bipolar disorder (BD) may provide new potential enhancements in treatment selection. Repeated total sleep deprivation combined with light therapy (TSD+LT) can acutely reverse depressive symptoms and has been proposed as a model antidepressant treatment. This study aims at investigating the effect of TSD+LT on effective connectivity and neural response in cortico-limbic circuitries during implicit processing of fearful and angry faces in patients with BD. fMRI and Dynamic Causal Modeling (DCM) were combined to study the effect of chronotherapeutics on neural responses in healthy controls (HC, n = 35) and BD patients either responder (RBD, n = 26) or non responder (nRBD, n = 11) to 3 consecutive TSD+LT sessions. Twenty-four DCMs exploring connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), Amygdala (Amy), fusiform gyrus and visual cortex were constructed. After treatment, patients significantly increased their neural responses in DLPFC, ACC and insula. nRBD showed lower baseline and endpoint neural responses than RBD. The increased activity in ACC and in medial prefrontal cortex, associated with antidepressant treatment, was positively associated with the improvement of depressive symptomatology. Only RBD patients increased intrinsic connectivity from DLPFC to ACC and reduced the modulatory effect of the task on Amy-DLPFC connection. A successful antidepressant treatment was associated with an increased functional activity and connectivity within cortico-limbic networks, suggesting the possible role of these measures in providing possible biomarkers for treatment efficacy. PMID:26195295

  10. Correlations between Limbic White Matter and Cognitive Function in Temporal-Lobe Epilepsy, Preliminary Findings

    PubMed Central

    Alexander, Ryan P. D.; Concha, Luis; Snyder, Thomas J.; Beaulieu, Christian; Gross, Donald William

    2014-01-01

    The limbic system is presumed to have a central role in cognitive performance, in particular memory. The purpose of this study was to investigate the relationship between limbic white matter microstructure and neuropsychological function in temporal-lobe epilepsy (TLE) patients using diffusion tensor imaging (DTI). Twenty-one adult TLE patients, including 7 non-lesional (nlTLE) and 14 with unilateral mesial temporal sclerosis (uTLE), were studied with both DTI and hippocampal T2 relaxometry. Correlations were performed between fractional anisotropy (FA) of the bilateral fornix and cingulum, hippocampal T2, neuropsychological tests. Positive correlations were observed in the whole group for the left fornix and processing speed index. In contrast, memory tests did not show significant correlations with DTI findings. Subgroup analysis demonstrated an association between the left fornix and processing speed in nlTLE but not uTLE. No correlations were observed between hippocampal T2 and test scores in either the TLE group as a whole or after subgroup analysis. Our findings suggest that integrity of the left fornix specifically is an important anatomical correlate of cognitive function in TLE patients, in particular patients with nlTLE. PMID:25071551

  11. Squamous Cell Lung Carcinoma Presenting With Refractory Status Epilepticus: A Case Report of Paraneoplastic Limbic Encephalitis.

    PubMed

    Hurley, Killian; Herron, Malcolm; McDermott, Sean; Farrell, Terence; O'Riordan, Deirdre

    2015-08-01

    Lung cancer-associated paraneoplastic syndromes affecting the central nervous system present significant diagnostic and treatment challenges. In this case, the patient presented with personality change, cognitive impairment, complex partial seizures, ataxia, dyspraxia, and dysphasia. Shortly after admission, the patient suffered refractory generalized tonic-clonic seizures and a decreased level of consciousness and required intubation, ventilation, and admission to the ICU. He was subsequently diagnosed with paraneoplastic limbic encephalitis based on recognized criteria, including a compatible clinical picture, elevated protein content in his cerebrospinal fluid with negative cytology, a positive positron emission tomography-computed tomography scan showing a right upper lobe tumor, and the exclusion of other neuro-oncological complications. Histopathology confirmed the tissue diagnosis as squamous cell cancer. Initial immunotherapy with steroids and intravenous immunoglobulin and subsequent lobectomy and adjuvant chemotherapy were partially successful, leading to partial resolution of his cognitive impairment. This report highlights the diagnostic and therapeutic challenges of lung-related paraneoplastic syndromes. In addition, it illustrates the poor outcomes for patients and identifies squamous cell cancer as an extremely rare cause of paraneoplastic limbic encephalitis. PMID:25784771

  12. [A Case of Acute Limbic Encephalitis with Sjögren's Syndrome].

    PubMed

    Shinmura, Hiroyuki; Nagasaka, Takamura; Tsuchiya, Mai; Onohara, Akiko; Takaki, Ryusuke; Takiyama, Yoshihisa

    2016-05-01

    A 52-year-old woman developed abnormal behavior and disturbance of consciousness subsequent to several days with a cold. On admission, she was very confused, with incoherent speech, and an inability to recognize family faces. Diffusion weighted MRI showed high intensity signal change in the bilateral medial temporal lobes, including the hippocampus. Cerebrospinal fluid examination was normal. Tests including various viral antibody titers provided no evidence of infection. Several neuronal antibodies including anti-VGKC and -NMDA receptor antibody were absent. Evidence of malignancy was not apparent. She was diagnosed with acute limbic encephalitis complicated by Sjögren's syndrome (SjS), due to the fact that she had a past history of SjS, elevation of anti-SS-A antibody, pleuritis and pericarditis. Her symptoms gradually improved after administration of steroids including pulse therapy; however, her amnesia remained for a long time. In diagnosing acute limbic encephalitis, we should consider SjS as an underlying disease, even though it is rare. PMID:27156510

  13. Diffusion tensor imaging in Alzheimer's disease: insights into the limbic-diencephalic network and methodological considerations

    PubMed Central

    Acosta-Cabronero, Julio; Nestor, Peter J.

    2014-01-01

    Glucose hypometabolism and gray matter atrophy are well known consequences of Alzheimer's disease (AD). Studies using these measures have shown that the earliest clinical stages, in which memory impairment is a relatively isolated feature, are associated with degeneration in an apparently remote group of areas—mesial temporal lobe (MTL), diencephalic structures such as anterior thalamus and mammillary bodies, and posterior cingulate. These sites are thought to be strongly anatomically inter-connected via a limbic-diencephalic network. Diffusion tensor imaging or DTI—an imaging technique capable of probing white matter tissue microstructure—has recently confirmed degeneration of the white matter connections of the limbic-diencephalic network in AD by way of an unbiased analysis strategy known as tract-based spatial statistics (TBSS). The present review contextualizes the relevance of these findings, in which the fornix is likely to play a fundamental role in linking MTL and diencephalon. An interesting by-product of this work has been in showing that alterations in diffusion behavior are complex in AD—while early studies tended to focus on fractional anisotropy, recent work has highlighted that this measure is not the most sensitive to early changes. Finally, this review will discuss in detail several technical aspects of DTI both in terms of image acquisition and TBSS analysis as both of these factors have important implications to ensure reliable observations are made that inform understanding of neurodegenerative diseases. PMID:25324775

  14. Striatal-Limbic Activation is Associated with Intensity of Anticipatory Anxiety

    PubMed Central

    Yang, Hongyu; Spence, Jeffrey S.; Devous, Michael D.; Briggs, Richard W.; Goyal, Aman; Xiao, Hong; Yadav, Hardik; Adinoff, Bryon

    2013-01-01

    Anxiety experienced in anticipation of impending aversive events induces striatal-limbic activation. However, previous functional magnetic imaging (fMRI) studies of anticipatory anxiety have utilized post-test measures of anxiety, making a direct association between neural activation and distress problematic. This paradigm was designed to assess the BOLD response to an aversive conditioned stimulus while simultaneously measuring subjective anxiety. Fifteen male healthy subjects (45.5±8.5 years old) were studied. A high threat conditioned stimulus (CS) was paired with either an unpredictable, highly aversive (painful) or a non-aversive (non-painful) unconditioned stimulus and compared to a low threat CS paired with a predictable, non-aversive stimulus. Neural response was assessed with fMRI, and subjective anxiety (1 to 4) was recorded upon the presentation of each CS. High subjective ratings of real-time anticipatory anxiety (2, 3, and 4), relative to low anticipatory anxiety (1), elicited increased activation in the bilateral striatum, bilateral orbital frontal cortex, left anterior insula, and anterior cingulate cortex (ACC) and decreased activation in the posterior cingulate cortex (PCC). The amplitude of BOLD signal change generally paralleled the subjective rating of anxiety. Real-time measures of anticipatory anxiety confirm previous reports, using post-test measures of anxiety, of striatal-limbic activation during anticipatory anxiety while simultaneously demonstrating an increase in BOLD response in parallel with heightened anxiety. PMID:23137803

  15. Naproxen, a Nonsteroidal Anti-Inflammatory Drug, Can Affect Daily Hypobaric Hypoxia-Induced Alterations of Monoamine Levels in Different Areas of the Brain in Male Rats.

    PubMed

    Goswami, Ananda Raj; Dutta, Goutam; Ghosh, Tusharkanti

    2016-06-01

    Goswami, Ananda Raj, Goutam Dutta, and Tusharkanti Ghosh. Naproxen, a nonsteroidal anti-inflammatory drug can affect daily hypobaric hypoxia-induced alterations of monoamine levels in different areas of the brain in male rats. High Alt Med Biol. 17:133-140, 2016.-The oxidative stress (OS)-induced prostaglandin (PG) release, in hypobaric hypoxic (HHc) condition, may be linked with the changes of brain monoamines. The present study intends to explore the changes of monoamines in hypothalamus (H), cerebral cortex (CC), and cerebellum (CB) along with the motor activity in rats after exposing them to simulated hypobaric condition and the role of PGs on the daily hypobaric hypoxia (DHH)-induced alteration of brain monoamines by administering, an inhibitor of PG synthesis, naproxen. The rats were exposed to a decompression chamber at 18,000 ft for 8 hours per day for 6 days after administration of vehicle or naproxen (18 mg/kg body wt.). The monoamine levels (epinephrine, E; norepinephrine, NE; dopamine, DA; and 5-hydroxytryptamine, 5-HT) in CC, CB, and H were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection, and the locomotor behavior was measured by open field test. The NE and DA levels were decreased in CC, CB, and H of the rat brain in HHc condition. The E and 5-HT levels were decreased in CC, but in H and CB, they remained unaltered in HHc condition. These DHH-induced changes of monoamines in brain areas were prevented after administration of naproxen in HHc condition. The locomotor behavior remained unaltered in HHc condition and after administration of naproxen in HHc condition. The DHH-induced changes of monoamines in the brain in HHc condition are probably linked with PGs that may be induced by OS. PMID:26894935

  16. An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images.

    PubMed

    Wiemerslage, Lyle; Nilsson, Emil K; Solstrand Dahlberg, Linda; Ence-Eriksson, Fia; Castillo, Sandra; Larsen, Anna L; Bylund, Simon B A; Hogenkamp, Pleunie S; Olivo, Gaia; Bandstein, Marcus; Titova, Olga E; Larsson, Elna-Marie; Benedict, Christian; Brooks, Samantha J; Schiöth, Helgi B

    2016-05-01

    Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight-loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low- or high-calorie food while brain activity was measured via fMRI. In a whole-brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non-risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing. PMID:26797854

  17. Organ distribution of quantum dots after intraperitoneal administration, with special reference to area-specific distribution in the brain

    NASA Astrophysics Data System (ADS)

    Kato, Shingo; Itoh, Kyoko; Yaoi, Takeshi; Tozawa, Takenori; Yoshikawa, Yutaka; Yasui, Hiroyuki; Kanamura, Narisato; Hoshino, Akiyoshi; Manabe, Noriyoshi; Yamamoto, Kenji; Fushiki, Shinji

    2010-08-01

    Quantum dots (QDs) are well known for their potential application in biosensing, ex vivo live-cell imaging and in vivo animal targeting. The brain is a challenging organ for drug delivery, because the blood brain barrier (BBB) functions as a gatekeeper guarding the body from exogenous substances. Here, we evaluated the distribution of bioconjugated QDs, i.e., captopril-conjugated QDs (QDs-cap) following intraperitoneal injection into male ICR mice as a model system for determining the tissue localization of QDs, employing ICP-MS and confocal microscopy coupled with spectrometric analysis. We have demonstrated that intraperitoneally administered QDs-cap were delivered via systemic blood circulation into liver, spleen, kidney and brain at 6 h after injection. QDs-cap were located predominantly inside the blood vessels in the liver, kidney and brain, but a few were distributed in the parenchyma, especially noteworthy in the brain. Careful studies on acute as well as chronic toxicity of QDs in the brain are required prior to clinical application to humans.

  18. Organ distribution of quantum dots after intraperitoneal administration, with special reference to area-specific distribution in the brain.

    PubMed

    Kato, Shingo; Itoh, Kyoko; Yaoi, Takeshi; Tozawa, Takenori; Yoshikawa, Yutaka; Yasui, Hiroyuki; Kanamura, Narisato; Hoshino, Akiyoshi; Manabe, Noriyoshi; Yamamoto, Kenji; Fushiki, Shinji

    2010-08-20

    Quantum dots (QDs) are well known for their potential application in biosensing, ex vivo live-cell imaging and in vivo animal targeting. The brain is a challenging organ for drug delivery, because the blood brain barrier (BBB) functions as a gatekeeper guarding the body from exogenous substances. Here, we evaluated the distribution of bioconjugated QDs, i.e., captopril-conjugated QDs (QDs-cap) following intraperitoneal injection into male ICR mice as a model system for determining the tissue localization of QDs, employing ICP-MS and confocal microscopy coupled with spectrometric analysis. We have demonstrated that intraperitoneally administered QDs-cap were delivered via systemic blood circulation into liver, spleen, kidney and brain at 6 h after injection. QDs-cap were located predominantly inside the blood vessels in the liver, kidney and brain, but a few were distributed in the parenchyma, especially noteworthy in the brain. Careful studies on acute as well as chronic toxicity of QDs in the brain are required prior to clinical application to humans. PMID:20660952

  19. Impaired Limbic Cortico-Striatal Structure and Sustained Visual Attention in a Rodent Model of Schizophrenia

    PubMed Central

    Barnes, Samuel A.; Sawiak, Stephen J.; Caprioli, Daniele; Jupp, Bianca; Buonincontri, Guido; Mar, Adam C.; Harte, Michael K.; Fletcher, Paul C.; Robbins, Trevor W.; Neill, Jo C.

    2015-01-01

    Background: N-methyl-d-aspartate receptor (NMDAR) dysfunction is thought to contribute to the pathophysiology of schizophrenia. Accordingly, NMDAR antagonists such as phencyclidine (PCP) are used widely in experimental animals to model cognitive impairment associated with this disorder. However, it is unclear whether PCP disrupts the structural integrity of brain areas relevant to the profile of cognitive impairment in schizophrenia. Methods: Here we used high-resolution magnetic resonance imaging and voxel-based morphometry to investigate structural alterations associated with sub-chronic PCP treatment in rats. Results: Sub-chronic exposure of rats to PCP (5mg/kg twice daily for 7 days) impaired sustained visual attention on a 5-choice serial reaction time task, notably when the attentional load was increased. In contrast, sub-chronic PCP had no significant effect on the attentional filtering of a pre-pulse auditory stimulus in an acoustic startle paradigm. Voxel-based morphometry revealed significantly reduced grey matter density bilaterally in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala. PCP-treated rats also exhibited reduced cortical thickness in the insular cortex. Conclusions: These findings demonstrate that sub-chronic NMDA receptor antagonism is sufficient to produce highly-localized morphological abnormalities in brain areas implicated in the pathogenesis of schizophrenia. Furthermore, PCP exposure resulted in dissociable impairments in attentional function. PMID:25552430

  20. Prefrontal vulnerabilities and whole brain connectivity in aging and depression

    PubMed Central

    Lamar, Melissa; Charlton, Rebecca A.; Ajilore, Olusola; Zhang, Aifeng; Yang, Shaolin; Barrick, Thomas R.; Rhodes, Emma; Kumar, Anand

    2013-01-01

    Studies exploring the underpinnings of age-related neurodegeneration suggest fronto-limbic alterations that are increasingly vulnerable in the presence of disease including late life depression. Less work has assessed the impact of this specific vulnerability on widespread brain circuitry. Seventy-nine older adults (healthy controls=45; late life depression=34) completed translational tasks shown in non-human primates to rely on fronto-limbic networks involving dorsolateral (Self-Ordered Pointing Task) or orbitofrontal (Object Alternation Task) cortices. A sub-sample of participants also completed diffusion tensor imaging for white matter tract quantification (uncinate and cingulum bundle; n=58) and whole brain tract-based spatial statistics (n=62). Despite task associations to specific white matter tracts across both groups, only healthy controls demonstrated significant correlations between widespread tract integrity and cognition. Thus, increasing Object Alternation Task errors were associated with decreasing fractional anisotropy in the uncinate in late life depression; however, only in healthy controls was the uncinate incorporated into a larger network of white matter vulnerability associating fractional anisotropy with Object Alternation Task errors using whole brain tract-based spatial statistics. It appears that the whole brain impact of specific fronto-limbic vulnerabilities in aging may be eclipsed in the presence of disease-specific neuropathology like that seen in late life depression. PMID:23680399

  1. Prefrontal vulnerabilities and whole brain connectivity in aging and depression.

    PubMed

    Lamar, Melissa; Charlton, Rebecca A; Ajilore, Olusola; Zhang, Aifeng; Yang, Shaolin; Barrick, Thomas R; Rhodes, Emma; Kumar, Anand

    2013-07-01

    Studies exploring the underpinnings of age-related neurodegeneration suggest fronto-limbic alterations that are increasingly vulnerable in the presence of disease including late life depression. Less work has assessed the impact of this specific vulnerability on widespread brain circuitry. Seventy-nine older adults (healthy controls=45; late life depression=34) completed translational tasks shown in non-human primates to rely on fronto-limbic networks involving dorsolateral (Self-Ordered Pointing Task) or orbitofrontal (Object Alternation Task) cortices. A sub-sample of participants also completed diffusion tensor imaging for white matter tract quantification (uncinate and cingulum bundle; n=58) and whole brain tract-based spatial statistics (n=62). Despite task associations to specific white matter tracts across both groups, only healthy controls demonstrated significant correlations between widespread tract integrity and cognition. Thus, increasing Object Alternation Task errors were associated with decreasing fractional anisotropy in the uncinate in late life depression; however, only in healthy controls was the uncinate incorporated into a larger network of white matter vulnerability associating fractional anisotropy with Object Alternation Task errors using whole brain tract-based spatial statistics. It appears that the whole brain impact of specific fronto-limbic vulnerabilities in aging may be eclipsed in the presence of disease-specific neuropathology like that seen in late life depression. PMID:23680399

  2. PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent

    SciTech Connect

    Tamminga, C.A.; Tanimoto, K.; Kuo, S.; Chase, T.N.; Contreras, P.C.; Rice, K.C.; Jackson, A.E.; O'Donohue, T.L.

    1987-01-01

    The effects of phencyclidine (PCP) on regional cerebral glucose utilization was determined by using quantitative autoradiography with (/sup 14/C)-2-deoxyglucose. PCP increased brain metabolism in selected areas of cortex, particularly limbic, and in the basal ganglia and thalamus, whereas the drug decreased metabolism in areas related to audition. These results are consistent with the known physiology of central PCP neurons and may help to suggest brain areas involved in PCP-mediated actions. Moreover, based on the behavioral similarities between PCP psychosis and an acute schizophrenic episode, these data may be relevant to the understanding of schizophrenia. The PCP-receptor-acylating agent, metaphit, blocked most of these PCP actions. In addition, metaphit by itself was found to diminish glucose utilization rather uniformly throughout brain. These results indicate an antagonist effect of metaphit on the PCP system and suggest a widespread action of metaphit, putatively at a PCP-related site, possibly in connection with the N-methyl-D-aspartate (NMDA) receptor.

  3. D-Amphetamine withdrawal-induced decreases in brain-derived neurotrophic factor in sprague-dawley rats are reversed by treatment with ketamine.

    PubMed

    Fuller, Jasmine J L; Murray, Ryan C; Horner, Kristen A

    2015-10-01

    Withdrawal from chronic D-amphetamine (D-AMPH) can induce negative emotional states, which may contribute to relapse and the maintenance of addiction. Diminished levels of brain-derived neurotrophic factor (BDNF), particularly in the hippocampus has been observed after exposure to stress, and recent data indicate that treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine may reverse these changes. However, it is unclear whether BDNF levels in the hippocampus or other regions of the limbic system are altered following the stress of D-AMPH withdrawal and it is not currently known if treatment with ketamine has any effect on these changes. The goals of this study were to examine BDNF levels throughout the limbic system following D-AMPH withdrawal and determine whether ketamine treatment would alter D-AMPH-induced changes in BDNF. Sprague-Dawley rats were treated with D-AMPH and BDNF protein examined in the prefrontal cortex, nucleus accumbens, amygdala and hippocampus at 24 h and 4 days of withdrawal. Our data show that at 24 h post-D-AMPH, BDNF levels were increased in the nucleus accumbens and decreased in the hippocampus. At 4 d post-D-AMPH, BDNF protein levels were decreased in all areas examined, and these decreases were reversed by treatment with ketamine. These data suggest that diminished BDNF may contribute to the negative affect seen following D-AMPH withdrawal, and that ketamine treatment could offer relief from these symptoms. PMID:25986696

  4. Correlation between neuronal antibodies and limbic encephalitis in Chinese Han subjects.

    PubMed

    Chen, Q M; Qu, H D; Qian, W D; Shen, L; Xu, L; Chen, Y H; Sang, D Q; Zhang, L N; Yin, L; Li, L; Wang, H

    2015-01-01

    A variety of anti-neuronal cell membrane antibodies such as voltage-gated potassium channel antibody, N-methyl-D-aspartate-2B-antibody, and glutamic acid decarboxylase antibody, are correlated with limbic encephalitis (LE). In this study on patients with LE, the clinical manifestations, psychology Wechsler Adult Intelligence Scale, cerebrospinal fluid, electrophysiology, magnetic resonance imaging, and anti-immune therapy were studied and immunological determination was conducted; it was found that patients of Chinese Han nationality showed 2 types of clinical manifestations: simple and complex. Lesions could also be divided into focal and scalable lesions, and the clinical manifestations and lesions scopes were associated with various antibodies and antibody types. The prognosis may improve if early diagnosis is conducted and early anti-immune therapy is implemented in LE patients. PMID:25867377

  5. Paraneoplastic Limbic Encephalitis in a Male with Squamous Cell Carcinoma of the Lung

    PubMed Central

    Sauri, Tamara; Izquierdo, Àngel; Ramió-Torrentà, LLuis; Sanchez-Montañez, Àngel; Bosch-Barrera, Joaquim

    2015-01-01

    Background Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, symptoms of hypothalamic dysfunction, and seizures. It commonly precedes the diagnosis of cancer. Small-cell lung cancer is the neoplasm that is most frequently reported as the etiology underlying PLE. Case Report This report describes a male patient who presented with neurologic symptoms consistent with anterograde amnesia, apathy, and disorientation. MRI revealed diffuse hyperintensities located predominantly in the medial bitemporal lobes, basal ganglia, frontal lobes, and leptomeninges on fluid attenuated inversion recovery images, suggesting PLE. Study of the primary tumor revealed squamous cell carcinoma of the lung. The patient was treated with neoadjuvant chemotherapy followed by surgery and adjuvant chemoradiotherapy, which resulted in his neurologic symptoms gradually improving. Conclusions PLE might be a rare debut of squamous cell carcinoma of the lung. Treatment of the primary tumor may improve the neurologic symptoms. PMID:25628742

  6. L-Theanine intake increases threshold for limbic seizures but decreases threshold for generalized seizures.

    PubMed

    Schallier, Anneleen; Vermoesen, Katia; Loyens, Ellen; Van Liefferinge, Joeri; Michotte, Yvette; Smolders, Ilse; Massie, Ann

    2013-03-01

    L-Theanine, an ethylamide derivate of glutamate found in abundance in green tea, has been shown to exert beneficial actions in animal models for several neurological disorders. We here investigated for the first time the effect of L-theanine intake on seizure susceptibility using acute pilocarpine and pentylenetetrazol (PTZ) mouse models for studying, respectively, limbic seizures or primarily generalized seizures. Moreover, we studied the effect of l-theanine intake on extracellular hippocampal and cortical glutamate and gamma-aminobutyric acid (GABA) levels, using in vivo microdialysis. Feeding mice with a 4% L-theanine solution significantly decreased their susceptibility to pilocarpine-induced seizures whereas susceptibility to PTZ-induced seizures was increased. The latter effect was linked to decreased extracellular GABA concentrations in frontal cortex. PMID:23324588

  7. Limbic Encephalitis Associated with Sjögren's Syndrome: Report of Three Cases.

    PubMed

    Çoban, Arzu; Özyurt, Selen; Meriç, Kaan; Mısırlı, Handan; Tüzün, Erdem; Türkoğlu, Recai

    2016-01-01

    Sjögren's syndrome (SS) may be complicated by neurological manifestations. We herein report three women (age range 26-60 years old) who all presented with limbic encephalitis (LE) as the predominant clinical feature 3 months to 15 years after the diagnosis of SS. The 26-year-old patient also developed acute motor axonal neuropathy one week after autoimmune encephalitis. All three patients showed contrast-enhanced MRI lesions and inflammatory cerebrospinal fluid findings, while not displaying any anti-neuronal antibodies and showing a remarkable response to immunotherapy. SS is often overlooked when the symptoms are mild. Therefore, in LE cases with no identifiable cause, serological screening for rheumatologic disorders is recommended. PMID:27523010

  8. Information fusion via isocortex-based Area 37 modeling

    NASA Astrophysics Data System (ADS)

    Peterson, James K.

    2004-08-01

    A simplified model of information processing in the brain can be constructed using primary sensory input from two modalities (auditory and visual) and recurrent connections to the limbic subsystem. Information fusion would then occur in Area 37 of the temporal cortex. The creation of meta concepts from the low order primary inputs is managed by models of isocortex processing. Isocortex algorithms are used to model parietal (auditory), occipital (visual), temporal (polymodal fusion) cortex and the limbic system. Each of these four modules is constructed out of five cortical stacks in which each stack consists of three vertically oriented six layer isocortex models. The input to output training of each cortical model uses the OCOS (on center - off surround) and FFP (folded feedback pathway) circuitry of (Grossberg, 1) which is inherently a recurrent network type of learning characterized by the identification of perceptual groups. Models of this sort are thus closely related to cognitive models as it is difficult to divorce the sensory processing subsystems from the higher level processing in the associative cortex. The overall software architecture presented is biologically based and is presented as a potential architectural prototype for the development of novel sensory fusion strategies. The algorithms are motivated to some degree by specific data from projects on musical composition and autonomous fine art painting programs, but only in the sense that these projects use two specific types of auditory and visual cortex data. Hence, the architectures are presented for an artificial information processing system which utilizes two disparate sensory sources. The exact nature of the two primary sensory input streams is irrelevant.

  9. Intrinsic brain indices of verbal working memory capacity in children and adolescents.

    PubMed

    Yang, Zhen; Jutagir, Devika R; Koyama, Maki S; Craddock, R Cameron; Yan, Chao-Gan; Shehzad, Zarrar; Castellanos, F Xavier; Di Martino, Adriana; Milham, Michael P

    2015-10-01

    Working memory (WM) is central to the acquisition of knowledge and skills throughout childhood and adolescence. While numerous behavioral and task-based functional magnetic resonance imaging (fMRI) studies have examined WM development, few have used resting-state fMRI (R-fMRI). Here, we present a systematic R-fMRI examination of age-related differences in the neural indices of verbal WM performance in a cross-sectional pediatric sample (ages: 7-17; n=68), using data-driven approaches. Verbal WM capacity was measured with the digit span task, a commonly used educational and clinical assessment. We found distinct neural indices of digit span forward (DSF) and backward (DSB) performance, reflecting their unique neuropsychological demands. Regardless of age, DSB performance was related to intrinsic properties of brain areas previously implicated in attention and cognitive control, while DSF performance was related to areas less commonly implicated in verbal WM storage (precuneus, lateral visual areas). From a developmental perspective, DSF exhibited more robust age-related differences in brain-behavior relationships than DSB, and implicated a broader range of networks (ventral attention, default, somatomotor, limbic networks)--including a number of regions not commonly associated with verbal WM (angular gyrus, subcallosum). These results highlight the importance of examining the neurodevelopment of verbal WM and of considering regions beyond the "usual suspects". PMID:26299314

  10. Neural reactivity to visual food stimuli is reduced in some areas of the brain during evening hours compared to morning hours: an fMRI study in women.

    PubMed

    Masterson, Travis D; Kirwan, C Brock; Davidson, Lance E; LeCheminant, James D

    2016-03-01

    The extent that neural responsiveness to visual food stimuli is influenced by time of day is not well examined. Using a crossover design, 15 healthy women were scanned using fMRI while presented with low- and high-energy pictures of food, once in the morning (6:30-8:30 am) and once in the evening (5:00-7:00 pm). Diets were identical on both days of the fMRI scans and were verified using weighed food records. Visual analog scales were used to record subjective perception of hunger and preoccupation with food prior to each fMRI scan. Six areas of the brain showed lower activation in the evening to both high- and low-energy foods, including structures in reward pathways (P < 0.05). Nine brain regions showed significantly higher activation for high-energy foods compared to low-energy foods (P < 0.05). High-energy food stimuli tended to produce greater fMRI responses than low-energy food stimuli in specific areas of the brain, regardless of time of day. However, evening scans showed a lower response to both low- and high-energy food pictures in some areas of the brain. Subjectively, participants reported no difference in hunger by time of day (F = 1.84, P = 0.19), but reported they could eat more (F = 4.83, P = 0.04) and were more preoccupied with thoughts of food (F = 5.51, P = 0.03) in the evening compared to the morning. These data underscore the role that time of day may have on neural responses to food stimuli. These results may also have clinical implications for fMRI measurement in order to prevent a time of day bias. PMID:25753781

  11. Effects of ractopamine feeding, gender and social rank on aggressiveness and monoamine concentrations in different brain areas of finishing pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study evaluated the effects of the feed additive ractopamine (RAC), gender and social rank on aggressiveness and brain monoamines levels of serotonin (5HT), dopamine (DA), their metabolites, norepinephrine (NE) and epinephrine (EP) in finishing pigs. Thirty-two pigs (16 barrows/16 gilts) were a...

  12. The human parental brain: In vivo neuroimaging

    PubMed Central

    Swain, James E.

    2015-01-01

    Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants’ current and future behavior. Indeed, the parent–infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust—likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain—from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health. PMID:21036196

  13. Genetic influences in emotional dysfunction and alcoholism-related brain damage

    PubMed Central

    Oscar-Berman, Marlene; Bowirrat, Abdalla

    2005-01-01

    Alcoholism is a complex, multifactorial disorder involving problematic ethanol ingestion; it results from the interplay between genetic and environmental factors. Personality, likewise, is formed from a combination of inherited and acquired influences. Because selected dimensions of emotional temperament are associated with distinct neurochemical substrates contributing to specific personality phenotypes, certain aspects of abnormal emotional traits in alcoholics may be inherited. Emotions involve complex subjective experiences engaging multiple brain regions, most notably the cortex, limbic system, and cerebellum. Results of in vivo magnetic resonance imaging and post-mortem neuropathological studies of alcoholics indicate that the greatest cortical loss occurs in the frontal lobes, with concurrent thinning of the corpus callosum. Additional damage has been documented for the amygdala and hippocampus, as well as in the white matter of the cerebellum. All of the critical areas of alcoholism-related brain damage are important for normal emotional functioning. When changes occur in these brain regions, either as a consequence of chronic ethanol abuse or from a genetic anomaly affecting temperament and/or a vulnerability to alcoholism, corresponding changes in emotional functions are to be expected. In alcoholics, such changes have been observed in their perception and evaluation of emotional facial expressions, interpretation of emotional intonations in vocal utterances, and appreciation of the meaning of emotional materials. PMID:18568071

  14. Increased number of TH-immunoreactive cells in the ventral tegmental area after deep brain stimulation of the anterior nucleus of the thalamus.

    PubMed

    Dela Cruz, J A D; Hescham, S; Adriaanse, B; Campos, F L; Steinbusch, H W M; Rutten, B P F; Temel, Y; Jahanshahi, A

    2015-09-01

    Dopamine (DA) has been long implicated with the processes of memory. In long-term memory, the hippocampus and ventral tegmental area (VTA) use DA to enhance long-term potentiation, while prefrontal DA D1 receptors are involved in working memory. Deep brain stimulation (DBS) of specific brain areas have been shown to affect memory impairments in animal models. Here, we tested the hypothesis that DBS could reverse memory impairments by increasing the number of dopaminergic cells in the VTA. Rats received DBS at the level of the mammillothalamic tract, the anterior nucleus of the thalamus, and entorhinal cortex before euthanasia. These regions are part of the so-called memory circuit. Brain sections were processed for c-Fos and tyrosine hydroxylase (TH) immunocytochemistry in the VTA and the substantia nigra pars compacta (SNc). c-Fos, TH and c-Fos/TH immunoreactive cells were analyzed by means of stereology and confocal microscopy. Our results showed that DBS of the anterior nucleus of the thalamus induced substantial higher numbers of TH-immunoreactive cells in the VTA, while there were no significant differences between the experimental groups in the number of TH immunoreactive cells in the SNc, c-Fos immunoreactive cells and c-Fos/TH double-labeled cells in both the SNc and VTA. Our findings suggest a phenotypic switch, or neurotransmitter respecification, of DAergic cells specifically in the VTA which may be induced by DBS in the anterior nucleus of the thalamus. PMID:25074751

  15. Sense and antisense transcripts of the developmentally regulated murine hsp70.2 gene are expressed in distinct and only partially overlapping areas in the adult brain

    NASA Technical Reports Server (NTRS)

    Murashov, A. K.; Wolgemuth, D. J.

    1996-01-01

    We have examined the spatial pattern of expression of a member of the hsp70 gene family, hsp70.2, in the mouse central nervous system. Surprisingly, RNA blot analysis and in situ hybridization revealed abundant expression of an 'antisense' hsp70.2 transcript in several areas of adult mouse brain. Two different transcripts recognized by sense and antisense riboprobes for the hsp70.2 gene were expressed in distinct and only partially overlapping neuronal populations. RNA blot analysis revealed low levels of the 2.7 kb transcript of hsp70.2 in several areas of the brain, with highest signal in the hippocampus. Abundant expression of a slightly larger (approximately 2.8 kb) 'antisense' transcript was detected in several brain regions, notably in the brainstem, cerebellum, mesencephalic tectum, thalamus, cortex, and hippocampus. In situ hybridization revealed that the sense and antisense transcripts were both predominantly neuronal and localized to the same cell types in the granular layer of the cerebellum, trapezoid nucleus of the superior olivary complex, locus coeruleus and hippocampus. The hsp70.2 antisense transcripts were particularly abundant in the frontal cortex, dentate gyrus, subthalamic nucleus, zona incerta, superior and inferior colliculi, central gray, brainstem, and cerebellar Purkinje cells. Our findings have revealed a distinct cellular and spatial localization of both sense and antisense transcripts, demonstrating a new level of complexity in the function of the heat shock genes.

  16. [Organization of the pallidal projections of the rostromedial tegmental nucleus in the dog brain].

    PubMed

    Gorbachevskaya, A I

    2014-01-01

    The method of retrograde and anterograde transport of horse-radish peroxidase was used to study the organization of the projections of the rostromedial tegmental nucleus (RMTN) to functionally distinct regions of pallidal structures of brain in dogs (n = 13). It was found that the fibers formed by the neurons of the limbic medial segments of RMTN rostral and caudal regions projected to the limbic pallidal regions--ventral globus pallidus and ventral pallidum. The reciprocal projections were detected between the ventral pallidum and medial segment of the rostral RMTN. These data indicate the possibility of the segregated conduction of the limbic information in the examined projection systems. However, in the majority of the pallidal structures, the convergence of the projection fibers originating from the neurons of functionally different parts of RMTN was observed. Thus, the projection fibers formed by the neurons of motor lateral and limbic medial parts of RMTN are directed to the limbic ventral segment of the globus pallidus and to the entopeduncular nucleus, which is innervated by the fibers formed by the neurons of functionally diverse structures. The possible pathways for conduction of functionally different information and its integration in the projection systems investigated are discussed. PMID:25823285

  17. Evaluation of brain perfusion in specific Brodmann areas in Frontotemporal dementia and Alzheimer disease using automated 3-D voxel based analysis

    NASA Astrophysics Data System (ADS)

    Valotassiou, V.; Papatriantafyllou, J.; Sifakis, N.; Karageorgiou, C.; Tsougos, I.; Tzavara, C.; Zerva, C.; Georgoulias, P.

    2009-05-01

    Introduction. Brain perfusion studies with single-photon emission computed tomography (SPECT) have been applied in demented patients to provide better discrimination between frontotemporal dementia (FTD) and Alzheimer's disease (AD). Aim. To assess the perfusion of specific Brodmann (Br) areas of the brain cortex in FTD and AD patients, using NeuroGam processing program to provide 3D voxel-by-voxel cerebral SPECT analysis. Material and methods. We studied 34 consecutive patients. We used the established criteria for the diagnosis of dementia and the specific established criteria for the diagnosis of FTD and AD. All the patients had a neuropsychological evaluation with a battery of tests including the mini-mental state examination (MMSE).Twenty-six patients (16 males, 10 females, mean age 68.76±6.51 years, education 11.81±4.25 years, MMSE 16.69±9.89) received the diagnosis of FTD and 8 patients (all females, mean age 71.25±10.48 years, education 10±4.6 years, MMSE 12.5±3.89) the diagnosis of AD. All the patients underwent a brain SPECT. We applied the NeuroGam Software for the evaluation of brain perfusion in specific Br areas in the left (L) and right (R) hemispheres. Results. Statistically significant hypoperfusion in FTD compared to AD patients, was found in the following Br areas: 11L (p<0.0001), 11R, 20L, 20R, 32L, 38L, 38R, 44L (p<0.001), 32R, 36L, 36R, 45L, 45R, 47R (p<0.01), 9L, 21L, 39R, 44R, 46R, 47L (p<0.05). On the contrary, AD patients presented significant (p<0.05) hypoperfusion in 7R and 39R Br areas. Conclusion. NeuroGam processing program of brain perfusion SPECT could result in enhanced accuracy for the differential diagnosis between AD and FTD patients.

  18. Pleasure systems in the brain

    PubMed Central

    Berridge, Kent C.; Kringelbach, Morten L.

    2015-01-01

    Pleasure is mediated by well-developed mesocorticolimbic circuitry, and serves adaptive functions. In affective disorders anhedonia (lack of pleasure) or dysphoria (negative affect) can result from breakdowns of that hedonic system. Human neuroimaging studies indicate that surprisingly similar circuitry is activated by quite diverse pleasures, suggesting a common neural currency shared by all. Wanting for rewards is generated by a large and distributed brain system. Liking, or pleasure itself, is generated by a smaller set of hedonic hotspots within limbic circuitry. Those hotspots also can be embedded in broader anatomical patterns of valence organization, such as in a keyboard pattern of nucleus accumbens generators for desire versus dread. In contrast, some of the best known textbook candidates for pleasure generators, including classic pleasure electrodes and the mesolimbic dopamine system, may not generate pleasure after all. These emerging insights into brain pleasure mechanisms may eventually facilitate better treatments for affective disorders. PMID:25950633

  19. Pleasure systems in the brain.

    PubMed

    Berridge, Kent C; Kringelbach, Morten L

    2015-05-01

    Pleasure is mediated by well-developed mesocorticolimbic circuitry and serves adaptive functions. In affective disorders, anhedonia (lack of pleasure) or dysphoria (negative affect) can result from breakdowns of that hedonic system. Human neuroimaging studies indicate that surprisingly similar circuitry is activated by quite diverse pleasures, suggesting a common neural currency shared by all. Wanting for reward is generated by a large and distributed brain system. Liking, or pleasure itself, is generated by a smaller set of hedonic hot spots within limbic circuitry. Those hot spots also can be embedded in broader anatomical patterns of valence organization, such as in a keyboard pattern of nucleus accumbens generators for desire versus dread. In contrast, some of the best known textbook candidates for pleasure generators, including classic pleasure electrodes and the mesolimbic dopamine system, may not generate pleasure after all. These emerging insights into brain pleasure mechanisms may eventually facilitate better treatments for affective disorders. PMID:25950633

  20. Brain Oscillations, Hypnosis, and Hypnotizability

    PubMed Central

    Jensen, Mark P.; Adachi, Tomonori; Hakimian, Shahin

    2014-01-01

    In this article, we summarize the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, and are usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. Here we propose that it is this role that may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis; specifically that theta oscillations may facilitate, and that changes in gamma activity observed with hypnosis may underlie, some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis, and for enhancing response to hypnotic treatments. PMID:25792761

  1. A pilot study into the effects of music therapy on different areas of the brain of individuals with unresponsive wakefulness syndrome.

    PubMed

    Steinhoff, Nikolaus; Heine, Astrid M; Vogl, Julia; Weiss, Konrad; Aschraf, Asita; Hajek, Paul; Schnider, Peter; Tucek, Gerhard

    2015-01-01

    The global cerebral network allows music " to do to us what it does." While the same music can cause different emotions, the basic emotion of happy and sad songs can, nevertheless, be understood by most people. Consequently, the individual experience of music and its common effect on the human brain is a challenging subject for research. Various activities such as hearing, processing, and performing music provide us with different pictures of cerebral centers in PET. In comparison to these simple acts of experiencing music, the interaction and the therapeutic relationship between the patient and the therapist in Music Therapy (MT) provide us with an additional element in need of investigation. In the course of a pilot study, these problems were approached and reduced to the simple observation of pattern alteration in the brains of four individuals with Unresponsive Wakefulness Syndrome (UWS) during MT. Each patient had three PET investigations: (i) during a resting state, (ii) during the first exposure to MT, and (iii) during the last exposure to MT. Two patients in the MT group received MT for 5 weeks between the 2nd and the 3rd PET (three times a week), while two other patients in the control group had no MT in between. Tracer uptake was measured in the frontal, hippocampal, and cerebellar region of the brain. With certain differences in these three observed brain areas, the tracer uptake in the MT group was higher (34%) than in the control group after 5 weeks. The preliminary results suggest that MT activates the three brain regions described above. In this article, we present our approach to the neuroscience of MT and discuss the impact of our hypothesis on music therapy practice, neurological rehabilitation of individuals in UWS and additional neuroscientific research. PMID:26347603

  2. A pilot study into the effects of music therapy on different areas of the brain of individuals with unresponsive wakefulness syndrome

    PubMed Central

    Steinhoff, Nikolaus; Heine, Astrid M.; Vogl, Julia; Weiss, Konrad; Aschraf, Asita; Hajek, Paul; Schnider, Peter; Tucek, Gerhard

    2015-01-01

    The global cerebral network allows music “ to do to us what it does.” While the same music can cause different emotions, the basic emotion of happy and sad songs can, nevertheless, be understood by most people. Consequently, the individual experience of music and its common effect on the human brain is a challenging subject for research. Various activities such as hearing, processing, and performing music provide us with different pictures of cerebral centers in PET. In comparison to these simple acts of experiencing music, the interaction and the therapeutic relationship between the patient and the therapist in Music Therapy (MT) provide us with an additional element in need of investigation. In the course of a pilot study, these problems were approached and reduced to the simple observation of pattern alteration in the brains of four individuals with Unresponsive Wakefulness Syndrome (UWS) during MT. Each patient had three PET investigations: (i) during a resting state, (ii) during the first exposure to MT, and (iii) during the last exposure to MT. Two patients in the MT group received MT for 5 weeks between the 2nd and the 3rd PET (three times a week), while two other patients in the control group had no MT in between. Tracer uptake was measured in the frontal, hippocampal, and cerebellar region of the brain. With certain differences in these three observed brain areas, the tracer uptake in the MT group was higher (34%) than in the control group after 5 weeks. The preliminary results suggest that MT activates the three brain regions described above. In this article, we present our approach to the neuroscience of MT and discuss the impact of our hypothesis on music therapy practice, neurological rehabilitation of individuals in UWS and additional neuroscientific research. PMID:26347603

  3. Functional brain activation during retrieval of visceral pain-conditioned passive avoidance in the rat.

    PubMed

    Wang, Zhuo; Bradesi, Sylvie; Charles, Jonathan R; Pang, Raina D; Maarek, Jean-Michel I; Mayer, Emeran A; Holschneider, Daniel P

    2011-12-01

    This study assessed functional brain activation in rats during expectation of visceral pain. Male rats were trained in step-down passive avoidance (PA) for 2 days. Upon stepping down from a platform, conditioned animals received noxious colorectal distension delivered through a colorectal balloon, whereas the balloon in control rats remained uninflated. On day 3, PA behavior was assessed while [(14)C]-iodoantipyrine was infused intravenously, followed by immediate euthanasia. Regional cerebral blood flow-related tissue radioactivity (rCBF) was analyzed by statistical parametric mapping using 3-dimensional brains reconstructed from autoradiographic brain slice images. Associated with retrieved PA behavior, conditioned rats compared with control subjects showed increases in rCBF in sensory (anterior insula, somatosensory cortex), limbic/paralimbic regions (anterior cingulate, prelimbic cortex, amygdala), all regions previously reported to show activation during acute visceral pain. Increases in rCBF were also noted in the dorsal hippocampus, nucleus accumbens, and caudate putamen, regions associated with retrieval of PA. Organization of the underlying brain network was further delineated by functional connectivity analysis. This revealed in conditioned rats a strongly and positively connected corticostriatal cluster (cingulate, prelimbic cortex, caudate putamen). The amygdala and cerebellar hemispheres formed another positively connected cluster, which was negatively connected with the corticostriatal cluster, suggesting corticolimbic modulation. Prelimbic cortex, nucleus accumbens, and anterior insula emerged in conditioned animals as hubs. Our results show that during retrieval of PA, brain areas implicated in PA expression as well as those implicated in acute visceral pain processing were recruited, in line with findings from human brain imaging studies on pain expectation. PMID:21944154

  4. Does somatosensory discrimination activate different brain areas in children with unilateral cerebral palsy compared to typically developing children? An fMRI study.

    PubMed

    Van de Winckel, Ann; Verheyden, Geert; Wenderoth, Nici; Peeters, Ron; Sunaert, Stefan; Van Hecke, Wim; De Cock, Paul; Desloovere, Kaat; Eyssen, Maria; Feys, Hilde

    2013-05-01

    Aside from motor impairment, many children with unilateral cerebral palsy (CP) experience altered tactile, proprioceptive, and kinesthetic awareness. Sensory deficits are addressed in rehabilitation programs, which include somatosensory discrimination exercises. In contrast to adult stroke patients, data on brain activation, occurring during somatosensory discrimination exercises, are lacking in CP children. Therefore, this study investigated brain activation with functional magnetic resonance imaging (fMRI) during passively guided somatosensory discrimination exercises in 18 typically developing children (TD) (age, M=14 ± 1.92 years; 11 girls) and 16 CP children (age, M=15 ± 2.54 years; 8 girls). The demographic variables between both groups were not statistically different. An fMRI compatible robot guided the right index finger and performed pairs of unfamiliar geometric shapes in the air, which were judged on their equality. The control condition comprised discrimination of music fragments. Both groups exhibited significant activation (FDR, p<.05) in frontoparietal, temporal, cerebellar areas, and insula, similar to studies in adults. The frontal areas encompassed ventral premotor areas, left postcentral gyrus, and precentral gyrus; additional supplementary motor area (SMA proper) activation in TD; as well as dorsal premotor, and parietal operculum recruitment in CP. On uncorrected level, p<.001, TD children revealed more left frontal lobe, and right cerebellum activation, compared to CP children. Conversely, CP children activated the left dorsal cingulate gyrus to a greater extent than TD children. These data provide incentives to investigate the effect of somatosensory discrimination during rehabilitation in CP, on clinical outcome and brain plasticity. PMID:23500165

  5. Schizophrenia and abnormal brain network hubs

    PubMed Central

    Rubinov, Mikail; Bullmore, Ed.

    2013-01-01

    Schizophrenia is a heterogeneous psychiatric disorder of unknown cause or characteristic pathology. Clinical neuroscientists increasingly postulate that schizophrenia is a disorder of brain network organization. In this article we discuss the conceptual framework of this dysconnection hypothesis, describe the predominant methodological paradigm for testing this hypothesis, and review recent evidence for disruption of central/hub brain regions, as a promising example of this hypothesis. We summarize studies of brain hubs in large-scale structural and functional brain networks and find strong evidence for network abnormalities of prefrontal hubs, and moderate evidence for network abnormalities of limbic, temporal, and parietal hubs. Future studies are needed to differentiate network dysfunction from previously observed gray- and white-matter abnormalities of these hubs, and to link endogenous network dysfunction phenotypes with perceptual, behavioral, and cognitive clinical phenotypes of schizophrenia. PMID:24174905

  6. Acute exposure to the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one induces oxidative stress in different brain area of rats.

    PubMed

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Guerra, Robson B; Dani, Caroline; Wannmacher, Clovis Milton Duval; Gomez, Rosane; Funchal, Cláudia

    2014-07-01

    The mechanisms that lead to the onset of organoselenium intoxication are still poorly understood. Therefore, in the present study, we investigated the effect of acute administration of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress and on the activity of creatine kinase (CK) in different brain areas and on the behaviour in the open field test of 90-day-old male rats. Animals (n = 10/group) were treated intraperitoneally with a single dose of the organoselenium (125, 250 or 500 µg kg(-1) ), and after 1 h of the drug administration, they were exposed to the open field test, and behaviour parameters were recorded. Immediately after they were euthanized, cerebral cortex, hippocampus and cerebellum were dissected for measurement of thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and CK activity. Our results showed that the dose of 500 µg kg(-1) of the organoselenium increased the locomotion and rearing behaviours in the open field test. Moreover, the organochalcogen enhanced TBARS in the cerebral cortex and cerebellum and increased the oxidation of proteins (carbonyl) only in the cerebral cortex. Sulfhydryl content was reduced in all brain areas, CAT activity enhanced in the hippocampus and reduced in the cerebellum and SOD activity increased in all brain structures. The organoselenium also inhibited CK activity in the cerebral cortex. Therefore, changes in motor behaviour, redox state and energy homeostasis in rats treated acutely with organoselenium support the hypotheses that the brain is a potential target for the organochalcogen action. Ltd. PMID:24633892

  7. Organochlorine contaminants in the muscle, liver and brain of seabirds (Larus) from the coastal area of the Southern Baltic.

    PubMed

    Falkowska, Lucyna; Reindl, Andrzej R; Grajewska, Agnieszka; Lewandowska, Anita U

    2016-11-01

    The presence of persistent organic pollutants in the environment manifests itself most strongly in the marine trophic chain, where the highest link is comprised of seabirds. At the same time, seabirds are excellent indicators of contamination in their habitat. The present study concentrates on toxic substances: polychlorinated dibenzo-p-dioxin (PCDDs), polychlorinated dibenzofurans (PCDFs) and chlorinated organic pesticides (OCPs) accumulated in the livers, pectoral muscles and brains of dead gulls collected along the Polish coast of the Baltic Sea in the years 2010-12. The highest toxic equivalence was determined in the livers of Larus argentatus (TEQ(birds TEF)-28.3pgg(-1) ww) and Larus marinus (TEQ(birds TEF)-29.9pgg(-1) ww.). However, the toxic equivalence of muscles was lower and amounted to 3.9pgg(-1) ww. and 7.8pgg(-1) ww. respectively for the two species. The lowest toxic equivalence was found in the brains of birds, where only one, the most toxic, 2,3,7,8 TCDD congener was found (TEQ(birds TEF) 0.87pgg(-1) ww). The highest concentration of chloroorganic pesticides was determined in the brains of the birds (total OCP 167.8pgg(-1) ww.), lower concentrations were found in the livers (total OCP 92.1pgg(-1) ww.) and muscles (total OCP 43.1pgg(-1) ww.). With regard to pesticides, the highest proportion in the total OCP content was constituted by DDT and its isomers (liver 81%, muscles 77% and brain 55%). High concentrations of the studied pollutants in the livers of gulls found dead on the coast of the Southern Baltic could have been effected by levels of contamination in the birds' last meals, which resulted in a seven-fold increase of the liver's toxic equivalence and a two-fold increase in OCP concentration in relation to muscles. PMID:27414257

  8. Global and regional brain volumes normalization in weight-recovered adolescents with anorexia nervosa: preliminary findings of a longitudinal voxel-based morphometry study

    PubMed Central

    Bomba, Monica; Riva, Anna; Morzenti, Sabrina; Grimaldi, Marco; Neri, Francesca; Nacinovich, Renata

    2015-01-01

    The recent literature on anorexia nervosa (AN) suggests that functional and structural abnormalities of cortico-limbic areas might play a role in the evolution of the disease. We explored global and regional brain volumes in a cross-sectional and follow-up study on adolescents affected by AN. Eleven adolescents with AN underwent a voxel-based morphometry study at time of diagnosis and immediately after weight recovery. Data were compared to volumes carried out in eight healthy, age and sex matched controls. Subjects with AN showed increased cerebrospinal fluid volumes and decreased white and gray matter volumes, when compared to controls. Moreover, significant regional gray matter decrease in insular cortex and cerebellum was found at time of diagnosis. No regional white matter decrease was found between samples and controls. Correlations between psychological evaluation and insular volumes were explored. After weight recovery gray matter volumes normalized while reduced global white matter volumes persisted. PMID:25834442

  9. Antinociception and behavioral changes induced by carbachol microinjected into identified sites of the rat brain.

    PubMed

    Klamt, J G; Prado, W A

    1991-05-17

    The sites of the rat brain in which intracerebral administration of carbachol (0.4 microgram/0.5 microliter) elevates the nociceptive threshold to thermic (tail-flick test) and mechanical (calibrated-pinch test) noxious stimuli were examined. An extensive mapping (510 sites) ranging from AP + 10.5 to AP-0.1 mm revealed that antinociception was obtained from 119 sites (23%) widely scattered in the brain, and reached structures distant from, or within the immediate vicinity of the ventricular system. The effects from most placement were demonstrated using the tail-flick test, whereas a smaller proportion (approximately 13%) of sites was effective in reducing the response to mechanical stimuli only. Structures containing sensitive sites include the dorsal raphe nucleus, lateral border of the superior cerebellar peduncle, caudal portion of the superior colliculus, medial geniculate body, habenular complex, amygdala, temporal pole of the ventral hippocampus, rostral aspect of the dorsal hippocampus, lateral septal area, and triangular nucleus of the septum. Analysis of the distribution of responsive sites indicated that they are poorly superposed to the known distribution of opiate-sensitive areas. Most of the structures found to be responsive to carbachol are also known to possess cholinergic receptors and to evoke antinociception following focal electrical stimulation. In various placements, particularly in limbic structures, microinjection of carbachol evoked jumping to mechanical noxious stimulation, hyperexcitability to non-noxious stimuli, convulsive reactions, and other less frequent reactions. On few occasions, however, these changes were accompanied by antinociception. PMID:1893255

  10. Reducing surface area while maintaining implant penetrating profile lowers the brain foreign body response to chronically implanted planar silicon microelectrode arrays.

    PubMed

    Skousen, John L; Merriam, Sr Mary Elizabeth; Srivannavit, Onnap; Perlin, Gaytri; Wise, Kensall D; Tresco, Patrick A

    2011-01-01

    A consistent feature of the foreign body response (FBR), irrespective of the type of implant, is persistent inflammation at the biotic-abiotic interface signaled by biomarkers of macrophage/microglial activation. Since macrophage-secreted factors shape the foreign body reaction, implant designs that reduce macrophage activation should improve biocompatibility and, with regard to recording devices, should improve reliability and longevity. At present, it is unclear whether the goal of seamless integration is possible or whether electrode developers can modulate specific aspects of the FBR by intentionally manipulating the constitutive properties of the implant. To explore this area, we studied the chronic brain FBR to planar solid silicon microelectrode arrays and planar lattice arrays with identical penetrating profiles but with reduced surface area in rats after an 8-week indwelling period. Using quantitative immunohistochemistry, we found that presenting less surface area after equivalent iatrogenic injury is accompanied by significantly less persistent macrophage activation, decreased blood brain barrier leakiness, and reduced neuronal cell loss. Our findings show that it is possible for implant developers to modulate specific aspects of the FBR by intentionally manipulating the constitutive properties of the implant. Our results also support the theory that the FBR to implanted electrode arrays, and likely other implants, can be explained by the presence of macrophages at the biotic-abiotic interface, which act as a sustained delivery source of bioactive agents that diffuse into the adjacent tissue and shape various features of the brain FBR. Further, our findings suggest that one method to improve the recording consistency and lifetime of implanted microelectrode arrays is to design implants that reduce the amount of macrophage activation at the biotic-abiotic interface and/or enhance the clearance or impact of their released factors. PMID:21867802

  11. Autoantibodies to epilepsy-related LGI1 in limbic encephalitis neutralize LGI1-ADAM22 interaction and reduce synaptic AMPA receptors.

    PubMed

    Ohkawa, Toshika; Fukata, Yuko; Yamasaki, Miwako; Miyazaki, Taisuke; Yokoi, Norihiko; Takashima, Hiroshi; Watanabe, Masahiko; Watanabe, Osamu; Fukata, Masaki

    2013-11-13

    More than 30 mutations in LGI1, a secreted neuronal protein, have been reported with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although LGI1 haploinsufficiency is thought to cause ADLTE, the underlying molecular mechanism that results in abnormal brain excitability remains mysterious. Here, we focused on a mode of action of LGI1 autoantibodies associated with limbic encephalitis (LE), which is one of acquired epileptic disorders characterized by subacute onset of amnesia and seizures. We comprehensively screened human sera from patients with immune-mediated neurological disorders for LGI1 autoantibodies, which also uncovered novel autoantibodies against six cell surface antigens including DCC, DPP10, and ADAM23. Our developed ELISA arrays revealed a specific role for LGI1 antibodies in LE and concomitant involvement of multiple antibodies, including LGI1 antibodies in neuromyotonia, a peripheral nerve disorder. LGI1 antibodies associated with LE specifically inhibited the ligand-receptor interaction between LGI1 and ADAM22/23 by targeting the EPTP repeat domain of LGI1 and reversibly reduced synaptic AMPA receptor clusters in rat hippocampal neurons. Furthermore, we found that disruption of LGI1-ADAM22 interaction by soluble extracellular domain of ADAM22 was sufficient to reduce synaptic AMPA receptors in rat hippocampal neurons and that levels of AMPA receptor were greatly reduced in the hippocampal dentate gyrus in the epileptic LGI1 knock-out mouse. Therefore, either genetic or acquired loss of the LGI1-ADAM22 interaction reduces the AMPA receptor function, causing epileptic disorders. These results suggest that by finely regulating the synaptic AMPA receptors, the LGI1-ADAM22 interaction maintains physiological brain excitability throughout life. PMID:24227725

  12. Autoantibodies to Epilepsy-Related LGI1 in Limbic Encephalitis Neutralize LGI1-ADAM22 Interaction and Reduce Synaptic AMPA Receptors

    PubMed Central

    Ohkawa, Toshika; Fukata, Yuko; Yamasaki, Miwako; Miyazaki, Taisuke; Yokoi, Norihiko; Takashima, Hiroshi; Watanabe, Masahiko; Watanabe, Osamu

    2013-01-01

    More than 30 mutations in LGI1, a secreted neuronal protein, have been reported with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although LGI1 haploinsufficiency is thought to cause ADLTE, the underlying molecular mechanism that results in abnormal brain excitability remains mysterious. Here, we focused on a mode of action of LGI1 autoantibodies associated with limbic encephalitis (LE), which is one of acquired epileptic disorders characterized by subacute onset of amnesia and seizures. We comprehensively screened human sera from patients with immune-mediated neurological disorders for LGI1 autoantibodies, which also uncovered novel autoantibodies against six cell surface antigens including DCC, DPP10, and ADAM23. Our developed ELISA arrays revealed a specific role for LGI1 antibodies in LE and concomitant involvement of multiple antibodies, including LGI1 antibodies in neuromyotonia, a peripheral nerve disorder. LGI1 antibodies associated with LE specifically inhibited the ligand-receptor interaction between LGI1 and ADAM22/23 by targeting the EPTP repeat domain of LGI1 and reversibly reduced synaptic AMPA receptor clusters in rat hippocampal neurons. Furthermore, we found that disruption of LGI1-ADAM22 interaction by soluble extracellular domain of ADAM22 was sufficient to reduce synaptic AMPA receptors in rat hippocampal neurons and that levels of AMPA receptor were greatly reduced in the hippocampal dentate gyrus in the epileptic LGI1 knock-out mouse. Therefore, either genetic or acquired loss of the LGI1-ADAM22 interaction reduces the AMPA receptor function, causing epileptic disorders. These results suggest that by finely regulating the synaptic AMPA receptors, the LGI1-ADAM22 interaction maintains physiological brain excitability throughout life. PMID:24227725

  13. Physics of the Brain: Interaction of the Optical-Fiber-Guided Multi-Ultraviolet-Photon Beams with the Epilepsy Topion, (the Seizure Onset Area)

    NASA Astrophysics Data System (ADS)

    Stefan, V. Alexander

    A novel method for the possible prevention of epileptic seizures is proposed, based on the multi-ultraviolet-photon beam interaction with the epilepsy topion, (nonlinear coupling of an ultra high frequency mode to the brain beta phonons). It is hypothesized that epilepsy is a chaotic-dynamics phenomenon: small electrical changes in the epilepsy-topion lead, (within the 10s of milliseconds), to the onset of chaos, (seizure--excessive electrical discharge), and subsequent cascading into adjacent areas. The ultraviolet photons may control the imbalance of sodium and potassium ions and, consequently, may prove to be efficient in the prevention of epileptic seizures. Supported by Nikola Tesla Labs, Stefan University.

  14. Immunocytochemical detection of newly generated neurons in the perilesional area of cortical infarcts after intraventricular application of brain-derived neurotrophic factor.

    PubMed

    Keiner, Silke; Witte, Otto W; Redecker, Christoph

    2009-01-01

    The adult brain responds to focal infarction with proliferation of glial subpopulations. In addition, cells that express the immature neuronal marker doublecortin have been found consistently in the perileisonal zone. We investigated whether application of brain-derived neurotrophic factor (BDNF) would influence this perilesional proliferative response. Photothrombotic infarcts were induced in the sensorimotor forelimb and hindlimb cortex of adult rats. Brain-derived neurotrophic factor or vehicle was continuously infused intraventricularly for 2 weeks after the infarct using osmotic minipumps. Proliferating cells were labeled by daily intraperitoneal injections of bromodeoxyuridine during the first 2 weeks and were quantified at days 14 and 42 using semiautomatic stereology. Triple immunofluorescence with antibodies against immature and mature neuronal and glial markers was used to identify the proliferating cell populations. On day 14 after intraventricular BNDF application, the numbers of doublecortin-positive cells were doubled in the perilesional zone. On day 42, BDNF-treated animals had a small number of mature neurons in these areas, whereas vehicle-treated controls did not. Behavioral analysis with a battery of sensorimotor tests revealed, however, that the alterations in the perilesional cellular response were not associated with an improved functional outcome. PMID:19104443

  15. Nicotine alters limbic function in adolescent rat by a 5-HT1A receptor mechanism.

    PubMed

    Dao, Jasmin M; McQuown, Susan C; Loughlin, Sandra E; Belluzzi, James D; Leslie, Frances M

    2011-06-01

    Epidemiological studies have shown that adolescent smoking is associated with health risk behaviors, including high-risk sexual activity and illicit drug use. Using rat as an animal model, we evaluated the behavioral and biochemical effects of a 4-day, low-dose nicotine pretreatment (60 μg/kg; intravenous) during adolescence and adulthood. Nicotine pretreatment significantly increased initial acquisition of cocaine self-administration, quinpirole-induced locomotor activity, and penile erection in adolescent rats, aged postnatal day (P)32. These effects were long lasting, remaining evident 10 days after the last nicotine treatment, and were observed when nicotine pretreatment was administered during early adolescence (P28-31), but not late adolescence (P38-41) or adulthood (P86-89). Neurochemical analyses of c-fos mRNA expression, and of monoamine transmitter and transporter levels, showed that forebrain limbic systems are continuing to develop during early adolescence, and that this maturation is critically altered by brief nicotine exposure. Nicotine selectively increased c-fos mRNA expression in the nucleus accumbens shell and basolateral amygdala in adolescent, but not adult animals, and altered serotonin markers in these regions as well as the prefrontal cortex. Nicotine enhancement of cocaine self-administration and quinpirole-induced locomotor activity was blocked by co-administration of WAY 100 635 (N-{2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl}-N-(2-pyridinyl)cyclohexanecarboxamide), a selective serotonin 1A (5-HT1A) receptor antagonist. Early adolescent pretreatment with the mixed autoreceptor/heteroceptor 5-HT1A receptor agonist, 8-OH-DPAT, but not the autoreceptor-selective agonist, S-15535, also enhanced quinpirole-induced locomotor activation. Nicotine enhancement of quinpirole-induced penile erection was not blocked by WAY 100 635 nor mimicked by 8-OH-DPAT. These findings indicate that early adolescent nicotine exposure uniquely alters limbic

  16. Changes in endocannabinoid and N-acylethanolamine levels in rat brain structures following cocaine self-administration and extinction training.

    PubMed

    Bystrowska, Beata; Smaga, Irena; Frankowska, Małgorzata; Filip, Małgorzata

    2014-04-01

    Preclinical investigations have demonstrated that drugs of abuse alter the levels of lipid-based signalling molecules, including endocannabinoids (eCBs) and N-acylethanolamines (NAEs), in the rodent brain. In addition, several drugs targeting eCBs and/or NAEs are implicated in reward and/or seeking behaviours related to the stimulation of dopamine systems in the brain. In our study, the brain levels of eCBs (anandamide (AEA) and 2-arachidonoylglycerol (2-AG)) and NAEs (oleoylethanolamide (OEA) and palmitoylethanolamide (PEA)) were analyzed via an LC-MS/MS method in selected brain structures of rats during cocaine self-administration and after extinction training according to the "yoked" control procedure. Repeated (14days) cocaine (0.5mg/kg/infusion) self-administration and yoked drug delivery resulted in a significant decrease (ca. 52%) in AEA levels in the cerebellum, whereas levels of 2-AG increased in the frontal cortex, the hippocampus and the cerebellum and decreased in the hippocampus and the dorsal striatum. In addition, we detected increases (>150%) in the levels of OEA and PEA in the limbic areas in both cocaine treated groups, as well as an increase in the tissue levels of OEA in the dorsal striatum in only the yoked cocaine group and increases in the tissue levels of PEA in the dorsal striatum (both cocaine groups) and the nucleus accumbens (yoked cocaine group only). Compared to the yoked saline control group, extinction training (10days) resulted in a potent reduction in AEA levels in the frontal cortex, the hippocampus and the nucleus accumbens and in 2-AG levels in the hippocampus, the dorsal striatum and the cerebellum. The decreases in the limbic and subcortical areas were more apparent for rats that self-administered cocaine. Following extinction, there was a region-specific change in the levels of NAEs in rats previously injected with cocaine; a potent increase (ca. 100%) in the levels of OEA and PEA was detected in the prefrontal cortex and the

  17. Design and Validation of a Novel Method to Measure Cross-Sectional Area of Neck Muscles Included during Routine MR Brain Volume Imaging

    PubMed Central

    Kilgour, Alixe H. M.; Subedi, Deepak; Gray, Calum D.; Deary, Ian J.; Lawrie, Stephen M.; Wardlaw, Joanna M.; Starr, John M.

    2012-01-01

    Introduction Low muscle mass secondary to disease and ageing is an important cause of excess mortality and morbidity. Many studies include a MR brain scan but no peripheral measure of muscle mass. We developed a technique to measure posterior neck muscle cross-sectional area (CSA) on volumetric MR brain scans enabling brain and muscle size to be measured simultaneously. Methods We performed four studies to develop and test: feasibility, inter-rater reliability, repeatability and external validity. We used T1-weighted MR brain imaging from young and older subjects, obtained on different scanners, and collected mid-thigh MR data. Results After developing the technique and demonstrating feasibility, we tested it for inter-rater reliability in 40 subjects. Intraclass correlation coefficients (ICC) between raters were 0.99 (95% confidence intervals (CI) 0.98–1.00) for the combined group (trapezius, splenius and semispinalis), 0.92 (CI 0.85–0.96) for obliquus and 0.92 (CI 0.85–0.96) for sternocleidomastoid. The first unrotated principal component explained 72.2% of total neck muscle CSA variance and correlated positively with both right (r = 0.52, p = .001) and left (r = 0.50, p = .002) grip strength. The 14 subjects in the repeatability study had had two MR brain scans on three different scanners. The ICC for between scanner variation for total neck muscle CSA was high at 0.94 (CI 0.86–0.98). The ICCs for within scanner variations were also high, with values of 0.95 (CI 0.86–0.98), 0.97 (CI 0.92–0.99) and 0.96 (CI 0.86–0.99) for the three scanners. The external validity study found a correlation coefficient for total thigh CSA and total neck CSA of 0.88. Discussion We present a feasible, valid and reliable method for measuring neck muscle CSA on T1-weighted MR brain scans. Larger studies are needed to validate and apply our technique with subjects differing in age, ethnicity and geographical location. PMID:22509305

  18. Bulk regional viral injection in neonatal mice enables structural and functional interrogation of defined neuronal populations throughout targeted brain areas

    PubMed Central

    Cheetham, Claire E. J.; Grier, Bryce D.; Belluscio, Leonardo

    2015-01-01

    The ability to label and manipulate specific cell types is central to understanding the structure and function of neuronal circuits. Here, we have developed a simple, affordable strategy for labeling of genetically defined populations of neurons throughout a targeted brain region: Bulk Regional Viral Injection (BReVI). Our strategy involves a large volume adeno-associated virus (AAV) injection in the targeted brain region of neonatal Cre driver mice. Using the mouse olfactory bulb (OB) as a model system, we tested the ability of BReVI to broadly and selectively label tufted cells, one of the two principal neuron populations of the OB, in CCK-IRES-Cre mice. BReVI resulted in labeling of neurons throughout the injected OB, with no spatial bias toward the injection site and no evidence of damage. The specificity of BReVI labeling was strikingly similar to that seen previously using immunohistochemical staining for cholecystokinin (CCK), an established tufted cell marker. Hence, the CCK-IRES-Cre line in combination with BReVI can provide an important tool for targeting and manipulation of OB tufted cells. We also found robust Cre-dependent reporter expression within three days of BReVI, which enabled us to assess developmental changes in the number and laminar distribution of OB tufted cells during the first three postnatal weeks. Furthermore, we demonstrate that BReVI permits structural and functional imaging in vivo, and can be combined with transgenic strategies to facilitate multi-color labeling of neuronal circuit components. BReVI is broadly applicable to different Cre driver lines and can be used to regionally manipulate genetically defined populations of neurons in any accessible brain region. PMID:26594154

  19. Quantitative Evaluation of Diffusion and Dynamic Contrast-Enhanced MR in Tumor Parenchyma and Peritumoral Area for Distinction of Brain Tumors

    PubMed Central

    Zhao, Jing; Yang, Zhi-yun; Luo, Bo-ning; Yang, Jian-yong; Chu, Jian-ping

    2015-01-01

    Purpose To quantitatively evaluate the diagnostic efficiency of parameters from diffusion and dynamic contrast-enhanced MR which based on tumor parenchyma (TP) and peritumoral (PT) area in classification of brain tumors. Methods 45 patients (male: 23, female: 22; mean age: 46 y) were prospectively recruited and they underwent conventional, DCE-MR and DWI examination. With each tumor, 10–15 regions of interest (ROIs) were manually placed on TP and PT area. ADC and permeability parameters (Ktrans, Ve, Kep and iAUC) were calculated and their diagnostic efficiency was assessed. Results In TP, all permeability parameters and ADC value could significantly discriminate Low- from High grade gliomas (HGG) (p<0.001); among theses parameters, Ve demonstrated the highest diagnostic power (iAUC: 0.79, cut-off point: 0.15); the most sensitive and specific index for gliomas grading were Ktrans (84%) and Kep (89%). While, in PT area, only Ktrans could help in gliomas grading (P = 0.009, cut-off point: 0.03 min-1). Moreover, in TP, mean Ve and iAUC of primary central nervous system lymphoma (PCNSL) and metastases were significantly higher than that in HGG (p<0.003). Further, in PT area, mean Ktrans (p≤0.004) could discriminate PCNSL from HGG and ADC (p≤0.003) could differentiate metastases with HGG. Conclusions Quantitative ADC and permeability parameters from Diffusion and DCE-MR in TP and PT area, especially DCE-MR, can aid in gliomas grading and brain tumors discrimination. Their combined application is strongly recommended in the differential diagnosis of these tumor entities. PMID:26384329

  20. An olfactory-limbic model of multiple chemical sensitivity syndrome: Possible relationships to kindling and affective spectrum disorders

    SciTech Connect

    Bell, I.R.; Miller, C.S.; Schwartz, G.E. )

    1992-08-01

    This paper reviews the clinical and experimental literature on patients with multiple adverse responses to chemicals (Multiple Chemical Sensitivity Syndrome-MCS) and develops a model for MCS based on olfactory-limbic system dysfunction that overlaps in part with Post's kindling model for affective disorders. MCS encompasses a broad range of chronic polysymptomatic conditions and complaints whose triggers are reported to include low levels of common indoor and outdoor environmental chemicals, such as pesticides and solvents. Other investigators have found evidence of increased prevalence of depression, anxiety, and somatization disorders in MCS patients and have concluded that their psychiatric conditions account for the clinical picture. However, none of these studies has presented any data on the effects of chemicals on symptoms or on objective measures of nervous system function. Synthesis of the MCS literature with large bodies of research in neurotoxicology, occupational medicine, and biological psychiatry, suggests that the phenomenology of MCS patients overlaps that of affective spectrum disorders and that both involve dysfunction of the limbic pathways. Animal studies demonstrate that intermittent repeated low level environmental chemical exposures, including pesticides, cause limbic kindling. Kindling (full or partial) is one central nervous system mechanism that could amplify reactivity to low levels of inhaled and ingested chemicals and initiate persistent affective, cognitive, and somatic symptomatology in both occupational and nonoccupational settings. As in animal studies, inescapable and novel stressors could cross-sensitize with chemical exposures in some individuals to generate adverse responses on a neurochemical basis. The olfactory-limbic model raises testable neurobiological hypotheses that could increase understanding of the multifactorial etiology of MCS and of certain overlapping affective spectrum disorders. 170 refs.

  1. The psychopath magnetized: insights from brain imaging.

    PubMed

    Anderson, Nathaniel E; Kiehl, Kent A

    2012-01-01

    Psychopaths commit a disproportionate amount of violent crime, and this places a substantial economic and emotional burden on society. Elucidation of the neural correlates of psychopathy may lead to improved management and treatment of the condition. Although some methodological issues remain, the neuroimaging literature is generally converging on a set of brain regions and circuits that are consistently implicated in the condition: the orbitofrontal cortex, amygdala, and the anterior and posterior cingulate and adjacent (para)limbic structures. We discuss these findings in the context of extant theories of psychopathy and highlight the potential legal and policy implications of this body of work. PMID:22177031

  2. The psychopath magnetized: insights from brain imaging

    PubMed Central

    Anderson, Nathaniel E.; Kiehl, Kent A.

    2014-01-01

    Psychopaths commit a disproportionate amount of violent crime, and this places a substantial economic and emotional burden on society. Elucidation of the neural correlates of psychopathy may lead to improved management and treatment of the condition. Although some methodological issues remain, the neuroimaging literature is generally converging on a set of brain regions and circuits that are consistently implicated in the condition: the orbitofrontal cortex, amygdala, and the anterior and posterior cingulate and adjacent (para)limbic structures. We discuss these findings in the context of extant theories of psychopathy and highlight the potential legal and policy implications of this body of work. PMID:22177031

  3. Atypical nucleus accumbens morphology in psychopathy: another limbic piece in the puzzle.

    PubMed

    Boccardi, Marina; Bocchetta, Martina; Aronen, Hannu J; Repo-Tiihonen, Eila; Vaurio, Olli; Thompson, Paul M; Tiihonen, Jari; Frisoni, Giovanni B

    2013-01-01

    Psychopathy has been associated with increased putamen and striatum volumes. The nucleus accumbens - a key structure in reversal learning, less effective in psychopathy - has not yet received specific attention. Moreover, basal ganglia morphology has never been explored. We examined the morphology of the caudate, putamen and accumbens, manually segmented from magnetic resonance images of 26 offenders (age: 32.5 ± 8.4) with medium-high psychopathy (mean PCL-R=30 ± 5) and 25 healthy controls (age: 34.6 ± 10.8). Local differences were statistically modeled using a surface-based radial distance mapping method (p<0.05; multiple comparisons correction through permutation tests). In psychopathy, the caudate and putamen had normal global volume, but different morphology, significant after correction for multiple comparisons, for the right dorsal putamen (permutation test: p=0.02). The volume of the nucleus accumbens was 13% smaller in psychopathy (p corrected for multiple comparisons <0.006). The atypical morphology consisted of predominant anterior hypotrophy bilaterally (10-30%). Caudate and putamen local morphology displayed negative correlation with the lifestyle factor of the PCL-R (permutation test: p=0.05 and 0.03). From these data, psychopathy appears to be associated with an atypical striatal morphology, with highly significant global and local differences of the accumbens. This is consistent with the clinical syndrome and with theories of limbic involvement. PMID:23399314

  4. A unique combination of autoimmune limbic encephalitis, type 1 diabetes, and Stiff person syndrome associated with GAD-65 antibody

    PubMed Central

    Sharma, Chandra Mohan; Pandey, Rajendra Kumar; Kumawat, Banshi Lal; Khandelwal, Dinesh; Gandhi, Pankaj

    2016-01-01

    Antibodies to GAD-65 have been implicated in the pathogenesis of type 1 diabetes, limbic encephalitis and Stiff person syndrome, however these diseases rarely occur concurrently. We intend to present a rare case of 35 year old female who was recently diagnosed as having type 1 diabetes presented with 1½ month history of recurrent seizures, subacute onset gait ataxia, dysathria, psychiatric disturbance and cognitive decline. No tumor was found on imaging and the classic paraneoplastic panel was negative. Cerebrospinal fluid and blood was positive for GAD-65 antibodies. Patient showed significant improvement with immunomodulatory therapy. Association of GAD-65 antibodies has been found with various disorders including type 1 diabetes, limbic encephalitis, Stiff person syndrome, cerebellar ataxia and palatal myoclonus. This case presents with unique combination of type 1 diabetes, Stiff person syndrome and limbic encephalitis associated with GAD-65 antibodies that is responsive to immunotherapy. It also highlights the emerging concept of autoimmunity in the causation of various disorders and there associations. PMID:27011652

  5. Fronto-limbic Function in Unaffected Offspring at Familial Risk for Bipolar Disorder during an Emotional Working Memory Paradigm

    PubMed Central

    Ladouceur, Cecile D.; Diwadkar, Vaibhav A.; White, Richard; Bass, Jeremy; Birmaher, Boris; Axelson, David A.; Phillips, Mary L.

    2013-01-01

    Evidence from neuroimaging studies indicate that individuals with bipolar disorder (BD) exhibit altered functioning of fronto-limbic systems implicated in voluntary emotion regulation. Few studies, however, have examined the extent to which unaffected youth at familial risk for BD exhibit such alterations. Using an fMRI emotional working memory paradigm, we investigated the functioning of fronto-limbic systems in fifteen healthy bipolar offspring (8–17 years old) with at least one parent diagnosed with BD (HBO), and 16 age-matched healthy control (HC) participants. Neural activity and functional connectivity analyses focused on a priori neural regions supporting emotion processing (amygdala, ventral striatum) and voluntary emotion regulation (ventrolateral prefrontal cortex (VLPFC), dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC)). Relative to HC, HBO exhibited greater right VLPFC (BA47) activation in response to positive emotional distracters and reduced VLPFC modulation of the amygdala to both the positive and negative emotional distracters; there were no group differences in connectivity for the neutral distracters. These findings suggest that alterations in the functioning of fronto-limbic systems implicated in voluntary emotion regulation are present in unaffected bipolar offspring. Future longitudinal studies are needed to determine the extent to which such alterations represent neurodevelopmental markers of risk for future onset of BD. PMID:23590840

  6. Cordocytes-stem cells cooperation in the human brain with emphasis on pivotal role of cordocytes in perivascular areas of broken and thrombosed vessels.

    PubMed

    Pais, Viorel; Danaila, Leon; Pais, Emil

    2013-12-01

    This study is based on data analysis by light and transmission electron microscopy of the surgical cases in cerebral tumors, cerebrovascular malformations, thromboses in the carotid system, and other injuries such as perivascular hemorrhage. We examined cortical arteries and veins, perivascular areas with old hematic masses, vasculogenic foci, and broken large vessels. We identified, characterized, and compared both undifferentiated cells and well-differentiated cordocytes within periadventitial areas where these cells cooperate very well with precursor/stem cells to perform vital functions for cerebral vasculature with immediate effect on brain parenchyma. This useful cellular cooperation was observed by serial sections pointing out the main role of cordocytes during the entire process of collateral vessel formation after thrombosis and, respectively, in vascular wall repair after ruptures. This is the first cytohistopathological study which illustrates and explains some facets of cordocytes-stem cells cooperation around the vessels of human brain with emphasis on the fundamental role of cordocytes in response to vascular injuries. Our pioneering study will be completed for both basic science and modern medical care by further studies. PMID:24205927

  7. Effects of stress, circadian rhythms, and dietary sodium on brain cell-nuclear uptake of aldosterone and corticosterone

    SciTech Connect

    Yongue, B.G.

    1985-01-01

    The binding of the adrenal steroid hormones aldosterone (ALD) and corticosterone (CORT) in brain cell-nuclei has been implicated as a necessary step in the behavioral and physiological actions of these hormones. In vivo uptake of radioactively labeled ALD and CORT in adrenalectomized (ADX) rats indicates a strong cell-nuclear localization of both of these hormones in limbic brain regions (such as hippocampus, septum and amygdala). Research using sub-cellular fractionation and radioimmunoassay (RIA), has confirmed both the presence of endogenously secreted CORT in cell-nuclei and its limbic localization in the brains of adrenal-intact rats. In this study, environmental and dietary factors were manipulated to induce variation in serum ALD and CORT. A series of experiments employing sub-cellular fractionation and RIA were performed, which reveal that: (1) endogenously secreted ALD and CORT, are concentrated by cell-nuclei of the brain in adrenal-intact rats, (2) the majority of the corticosteroids measured in ethanol extracts of brain cell-nuclei are associated with receptor molecules, and (3) the regional distribution of endogenously secreted ALD differs markedly from the predominantly limbic pattern predicted from in vivo uptake of labeled ALD in ADX rats. Instead, brain cell-nuclear ALD is heavily concentrated in the hypothalamus, which supports the hypothesized relationship between the interaction of ALD and angiotensin in the brain and the behavioral regulation of fluid/electrolyte balance.

  8. Morphological brain network assessed using graph theory and network filtration in deaf adults.

    PubMed

    Kim, Eunkyung; Kang, Hyejin; Lee, Hyekyoung; Lee, Hyo-Jeong; Suh, Myung-Whan; Song, Jae-Jin; Oh, Seung-Ha; Lee, Dong Soo

    2014-09-01

    Prolonged deprivation of auditory input can change brain networks in pre- and postlingual deaf adults by brain-wide reorganization. To investigate morphological changes in these brains voxel-based morphometry, voxel-wise correlation with the primary auditory cortex, and whole brain network analyses using morphological covariance were performed in eight prelingual deaf, eleven postlingual deaf, and eleven hearing adults. Network characteristics based on graph theory and network filtration based on persistent homology were examined. Gray matter density in the primary auditor cortex was preserved in prelingual deafness, while it tended to decrease in postlingual deafness. Unlike postlingual, prelingual deafness showed increased bilateral temporal connectivity of the primary auditory cortex compared to the hearing adults. Of the graph theory-based characteristics, clustering coefficient, betweenness centrality, and nodal efficiency all increased in prelingual deafness, while all the parameters of postlingual deafness were similar to the hearing adults. Patterns of connected components changing during network filtration were different between prelingual deafness and hearing adults according to the barcode, dendrogram, and single linkage matrix representations, while these were the same in postlingual deafness. Nodes in fronto-limbic and left temporal components were closely coupled, and nodes in the temporo-parietal component were loosely coupled, in prelingual deafness. Patterns of connected components changing in postlingual deafness were the same as hearing adults. We propose that the preserved density of auditory cortex associated with increased connectivity in prelingual deafness, and closer coupling between certain brain areas, represent distinctive reorganization of auditory and related cortices compared with hearing or postlingual deaf adults. The differential network reorganization in the prelingual deaf adults could be related to the absence of auditory speech

  9. Objects tell us what action we can expect: dissociating brain areas for retrieval and exploitation of action knowledge during action observation in fMRI

    PubMed Central

    Schubotz, Ricarda I.; Wurm, Moritz F.; Wittmann, Marco K.; von Cramon, D. Yves

    2014-01-01

    Objects are reminiscent of actions often performed with them: knife and apple remind us on peeling the apple or cutting it. Mnemonic representations of object-related actions (action codes) evoked by the sight of an object may constrain and hence facilitate recognition of unrolling actions. The present fMRI study investigated if and how action codes influence brain activation during action observation. The average number of action codes (NAC) of 51 sets of objects was rated by a group of n = 24 participants. In an fMRI study, different volunteers were asked to recognize actions performed with the same objects presented in short videos. To disentangle areas reflecting the storage of action codes from those exploiting them, we showed object-compatible and object-incompatible (pantomime) actions. Areas storing action codes were considered to positively co-vary with NAC in both object-compatible and object-incompatible action; due to its role in tool-related tasks, we here hypothesized left anterior inferior parietal cortex (aIPL). In contrast, areas exploiting action codes were expected to show this correlation only in object-compatible but not incompatible action, as only object-compatible actions match one of the active action codes. For this interaction, we hypothesized ventrolateral premotor cortex (PMv) to join aIPL due to its role in biasing competition in IPL. We found left anterior intraparietal sulcus (IPS) and left posterior middle temporal gyrus (pMTG) to co-vary with NAC. In addition to these areas, action codes increased activity in object-compatible action in bilateral PMv, right IPS, and lateral occipital cortex (LO). Findings suggest that during action observation, the brain derives possible actions from perceived objects, and uses this information to shape action recognition. In particular, the number of expectable actions quantifies the activity level at PMv, IPL, and pMTG, but only PMv reflects their biased competition while observed action unfolds

  10. GATA4 variant interaction with brain limbic structure and relapse risk: A voxel-based morphometry study.

    PubMed

    Zois, Evangelos; Vollstädt-Klein, Sabine; Hoffmann, Sabine; Reinhard, Iris; Bach, Patrick; Charlet, Katrin; Beck, Anne; Treutlein, Jens; Frank, Josef; Jorde, Anne; Kirsch, Martina; Degenhardt, Franziska; Walter, Henrik; Heinz, Andreas; Kiefer, Falk

    2016-09-01

    Atrial natriuretic peptide (ANP) receptors are highly expressed in the amygdala, caudate and hypothalamus. GATA4 gene encodes a transcription factor of ANP associated with the pathophysiology of alcohol dependence. We have previously demonstrated that the GATA4 single nucleotide polymorphism (SNP) rs13273672 revealed stronger alcohol-specific amygdala activation associated with lowered relapse risk to heavy drinking at 90 days in the AA-homozygotes. Our understanding however with respect to GATA4 variation on gray matter (GM) regional amygdala, caudate and hypothalamus volume is limited. We investigated GM differences specific to GATA4 and hypothesized that GM alterations will be predictive of heavy relapse. Eighty-three recently detoxified alcohol dependent patients were included. Neuroimaging data was analyzed using Voxel Based Morphometry (VBM). The main effects of GM volume and genotype as well as their interaction effect on time to heavy relapse (60 and 90 days) were analyzed using cox regression. Significant higher GM volume was found for the AA-genotype group compared with AG/GG-genotype in the hypothalamus and caudate. A significant interaction was revealed between caudate and amygdala GM volume and GATA4 genotype on time to heavy relapse. The interaction was expressed by means of higher GM in the AA genotype group to be associated with reduced risk to relapse whereas in the AG/GG group higher GM was associated with increased risk to relapse. This is the first report on GM regional volume alterations specific to GATA4 genotype [(SNP) rs13273672] and its association with relapse in alcohol dependence. Current findings further support the role of GATA4 in alcoholism. PMID:27397865

  11. The importance of the context in the hippocampus and brain related areas throughout the performance of a fear conditioning task.

    PubMed

    Arias, Natalia; Méndez, Marta; Arias, Jorge L

    2015-11-01

    The importance context has been broadly studied in the management of phobias and in the drug addiction literature. The way in which changes to a context influence behavior after the simple acquisition of a passive avoidance task remains unclear. The hippocampus has long been implicated in the contextual and spatial processing required for contextual fear, but its role in encoding the aversive component of a contextual fear memory is still inconclusive. Our work tries to elucidate whether a change in context, represented as differences in the load of the stimuli, is critical for learning about the context-shock association and whether this manipulation of the context could be linked to any change in metabolic brain activity requirements. For this purpose, we used an avoidance conditioning task. Animals were divided into three different experimental conditions. In one group, acquisition was performed in an enriched stimuli environment and retention was performed in a typically lit chamber (the PA-ACQ-CONTX group). In another group, acquisition was performed in the typically lit chamber and retention was undertaken in the highly enriched chamber (the PA-RET-CONTX group). Finally, for the control group, PA-CN-CONTX, acquisition, and retention were performed in the enriched stimuli environment. Our results showed that the PA-ACQ-CONTX group had longer escape latencies and poorer retention than the PA-RET-CONTX and PA-CN-CONTX groups after 24 h of acquisition under contextual changes. To study metabolic brain activity, histochemical labelling of cytochrome c-oxidase (CO) was performed. CO results suggested a neural circuit including the hippocampus, amygdala, thalamus, parahippocampal cortices, and mammillary nuclei that is involved in the learning and memory processes that enable context-dependent behavior. These results highlight how dysfunction in this network may be involved in the contextualization of fear associations that underlie several forms of psychopathology

  12. Abnormal Activation of the Social Brain Network in Children with Autism Spectrum Disorder: An fMRI Study

    PubMed Central

    Kim, Sun-Young; Choi, Uk-Su; Park, Sung-Yeon; Oh, Se-Hong; Yoon, Hyo-Woon; Koh, Yun-Joo; Im, Woo-Young; Park, Jee-In; Song, Dong-Ho

    2015-01-01

    Objective The aim of this study is to investigate abnormal findings of social brain network in Korean children with autism spectrum disorder (ASD) compared with typically developing children (TDC). Methods Functional magnetic resonance imaging (fMRI) was performed to examine brain activations during the processing of emotional faces (happy, fearful, and neutral) in 17 children with ASD, 24 TDC. Results When emotional face stimuli were given to children with ASD, various areas of the social brain relevant to social cognition showed reduced activation. Specifically, ASD children exhibited less activation in the right amygdala (AMY), right superior temporal sulcus (STS) and right inferior frontal gyrus (IFG) than TDC group when fearful faces were shown. Activation of left insular cortex and right IFG in response to happy faces was less in the ASD group. Similar findings were also found in left superior insular gyrus and right insula in case of neutral stimulation. Conclusion These findings suggest that children with ASD have different processing of social and emotional experience at the neural level. In other words, the deficit of social cognition in ASD could be explained by the deterioration of the capacity for visual analysis of emotional faces, the subsequent inner imitation through mirror neuron system (MNS), and the ability to transmit it to the limbic system and to process the transmitted emotion. PMID:25670944

  13. Brain and Cognition Abnormalities in Long-Term Anabolic-Androgenic Steroid Users

    PubMed Central

    Kaufman, Marc J.; Janes, Amy C.; Hudson, James I.; Brennan, Brian P.; Kanayama, Gen; Kerrigan, Andrew R.; Jensen, J. Eric; Pope, Harrison G.

    2015-01-01

    Background Anabolic-androgenic steroid (AAS) use is associated with psychiatric symptoms including increased aggression as well as with cognitive dysfunction. The brain effects of long-term AAS use have not been assessed in humans. Methods This multimodal magnetic resonance imaging study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure. Participants were administered visuospatial memory tests and underwent neuroimaging. Brain volumetric analyses were performed; resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of-interest analysis focused on the amygdala; and dorsal anterior cingulate cortex (dACC) metabolites were quantified by proton magnetic resonance spectroscopy (MRS). Results AAS users had larger right amygdala volumes than nonusers (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas. Left amygdala volumes were slightly larger in AAS users (P=0.061) but few group differences were detected in left amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased glutamate turnover. On a visuospatial cognitive task, AAS users performed more poorly than nonusers, with the difference approaching significance (P=0.053). Conclusions Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction. PMID:25986964

  14. Sexual Dimorphism in the Brain of the Monogamous California Mouse (Peromyscus californicus).

    PubMed

    Campi, Katharine L; Jameson, Chelsea E; Trainor, Brian C

    2013-01-01

    Sex differences in behavior and morphology are usually assumed to be stronger in polygynous species compared to monogamous species. A few brain structures have been identified as sexually dimorphic in polygynous rodent species, but it is less clear whether these differences persist in monogamous species. California mice are among the 5% or less of mammals that are considered to be monogamous and as such provide an ideal model to examine sexual dimorphism in neuroanatomy. In the present study we compared the volume of hypothalamic- and limbic-associated regions in female and male California mice for sexual dimorphism. We also used tyrosine hydroxylase (TH) immunohistochemistry to compare the number of dopamine neurons in the ventral tegmental area (VTA) in female and male California mice. Additionally, tract tracing was used to accurately delineate the boundaries of the VTA. The total volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA), the principal nucleus of the bed nucleus of the stria terminalis (BNST), and the posterodorsal medial amygdala (MEA) was larger in males compared to females. In the SDN-POA we found that the magnitude of sex differences in the California mouse were intermediate between the large differences observed in promiscuous meadow voles and rats and the absence of significant differences in monogamous prairie voles. However, the magnitude of sex differences in MEA and the BNST were comparable to polygynous species. No sex differences were observed in the volume of the whole brain, the VTA, the nucleus accumbens or the number of TH-ir neurons in the VTA. These data show that despite a monogamous social organization, sexual dimorphisms that have been reported in polygynous rodents extend to California mice. Our data suggest that sex differences in brain structures such as the SDN-POA persist across species with different social organizations and may be an evolutionarily conserved characteristic of mammalian brains. PMID

  15. Brain organization in a reptile lacking sex chromosomes: effects of gonadectomy and exogenous testosterone.

    PubMed

    Crews, D; Coomber, P; Baldwin, R; Azad, N; Gonzalez-Lima, F

    1996-12-01

    In mammals, males and females differ both genetically and hormonally, making it difficult to assess the relative contributions of genetic constitution and fetal environment in the process of sexual differentiation. Many reptiles lack sex chromosomes, relying instead on the temperature of incubation to determine sex. In the leopard gecko (Eublepharis macularius), an incubation temperature of 26 degrees C produces all females, whereas 32.5 degrees C results in mostly males. Incubation temperature is the primary determinant of differences both within and between the sexes in growth, physiology, and sociosexual behavior, as well as the volume and metabolic capacity of specific brain nuclei. To determine if incubation temperature organizes the brain directly rather than via gonadal sex hormones, the gonads of male and female leopard geckos from the two incubation temperatures were removed and, in some instances, animals were given exogenous testosterone. In vertebrates with sex chromosomes, the size of sexually dimorphic nuclei are sensitive to hormone levels in adulthood, but in all species studied to date, these changes are restricted to the male. Therefore, after behavior tests, morphometrics of certain limbic and nonlimbic brain areas were determined. Because nervous system tissue depends on oxidative metabolism for energy production and the level of cytochrome oxidase activity is coupled to the functional level of neuronal activity, cytochrome oxidase histochemistry also was performed on the same brains. Hormonal manipulation had little effect on the volume of the preoptic area or ventromedial hypothalamus in geckos from the all-female incubation temperature, but significantly influenced the volumes of these brain areas in males and females from the male-biased incubation temperature. A similar relationship was found for cytochrome oxidase activity of the anterior hypothalamus, amygdala, dorsal ventricular ridge, and septum. The only sex difference observed was

  16. Memory enhancement induced by hypothalamic/fornix deep brain stimulation.

    PubMed

    Hamani, Clement; McAndrews, Mary Pat; Cohn, Melanie; Oh, Michael; Zumsteg, Dominik; Shapiro, Colin M; Wennberg, Richard A; Lozano, Andres M

    2008-01-01

    Bilateral hypothalamic deep brain stimulation was performed to treat a patient with morbid obesity. We observed, quite unexpectedly, that stimulation evoked detailed autobiographical memories. Associative memory tasks conducted in a double-blinded "on" versus "off" manner demonstrated that stimulation increased recollection but not familiarity-based recognition, indicating a functional engagement of the hippocampus. Electroencephalographic source localization showed that hypothalamic deep brain stimulation drove activity in mesial temporal lobe structures. This shows that hypothalamic stimulation in this patient modulates limbic activity and improves certain memory functions. PMID:18232017

  17. A greater involvement of posterior brain areas in interhemispheric transfer in autism: fMRI, DWI and behavioral evidences

    PubMed Central

    Barbeau, Elise B.; Lewis, John D.; Doyon, Julien; Benali, Habib; Zeffiro, Thomas A.; Mottron, Laurent

    2015-01-01

    A small corpus callosum (CC) is one of the most replicated neurobiological findings in autism spectrum (AS). However, its effect on interhemispheric (IH) communication is unknown. We combined structural (CC area and DWI), functional (task-related fMRI activation and connectivity analyses) as well as behavioral (Poffenberger and Purdue tasks) measures to investigate IH integration in adult AS individuals of typical intelligence. Despite similar behavioral IH transfer time and performances in bimanual tasks, the CC sub-regions connecting frontal and parietal cortical areas were smaller in AS than in non-AS individuals, while those connecting visual regions were similar. The activation of visual areas was lower in AS than in non-AS individuals during the presentation of visual stimuli. Behavioral IH performances were related to the properties of CC subregions connecting motor areas in non-AS individuals, but to the properties of posterior CC regions in AS individuals. Furthermore, there was greater functional connectivity between visual areas in the AS than in the non-AS group. Levels of connectivity were also stronger in visual than in motor regions in the autistic subjects, while the opposite was true for the non-autistic group. Thus, visual IH transfer plays an important role in visuo-motor tasks in AS individuals. These findings extend the well established enhanced role of perception in autistic cognition to visuo-motor IH information transfer. PMID:26106551

  18. Different contributions of visual and motor brain areas during liking judgments of same- and different-gender bodies.

    PubMed

    Cazzato, V; Mele, S; Urgesi, C

    2016-09-01

    Previous neuroimaging studies have shown that body aesthetic appreciation involves the activation of both visual and motor areas, supporting a role of sensorimotor embodiment in aesthetic processing. Causative evidence, however, that neural activity in these areas is crucial for reliable aesthetic body appreciation has so far provided only for extrastriate body area (EBA), while the functional role played by premotor regions remained less clear. Here, we applied short trains of repetitive transcranial magnetic stimulation (rTMS) over bilateral dorsal premotor cortex (dPMC) and EBA during liking judgments of female and male bodies varying in weight and implied motion. We found that both dPMC and EBA are necessary for aesthetic body appreciation, but their relative contribution depends on the model's gender. While dPMC-rTMS decreased the liking judgments of same-, but not of different-gender models, EBA-rTMS increased the liking judgments of different-, but not of same-gender models. Relative contributions of motor and visual areas may reflect processing of diverse aesthetic properties, respectively implied motion vs. body form, and/or greater sensorimotor embodiment of same- vs. different-gender bodies. Results suggest that aesthetic body processing is subserved by a network of motor and visual areas, whose relative contribution may depend on the specific stimulus and task. PMID:27235869

  19. Enduring deficits in memory and neuronal pathology after blast-induced traumatic brain injury

    PubMed Central

    Sajja, Venkata Siva Sai Sujith; Hubbard, W. Brad; Hall, Christina S.; Ghoddoussi, Farhad; Galloway, Matthew P.; VandeVord, Pamela J.

    2015-01-01

    Few preclinical studies have assessed the long-term neuropathology and behavioral deficits after sustaining blast-induced neurotrauma (BINT). Previous studies have shown extensive astrogliosis and cell death at acute stages (<7 days) but the temporal response at a chronic stage has yet to be ascertained. Here, we used behavioral assays, immmunohistochemistry and neurochemistry in limbic areas such as the amygdala (Amy), Hippocampus (Hipp), nucleus accumbens (Nac), and prefrontal cortex (PFC), to determine the long-term effects of a single blast exposure. Behavioral results identified elevated avoidance behavior and decreased short-term memory at either one or three months after a single blast event. At three months after BINT, markers for neurodegeneration (FJB) and microglia activation (Iba-1) increased while index of mature neurons (NeuN) significantly decreased in all brain regions examined. Gliosis (GFAP) increased in all regions except the Nac but only PFC was positive for apoptosis (caspase-3). At three months, tau was selectively elevated in the PFC and Hipp whereas α-synuclein transiently increased in the Hipp at one month after blast exposure. The composite neurochemical measure, myo-inositol+glycine/creatine, was consistently increased in each brain region three months following blast. Overall, a single blast event resulted in enduring long-term effects on behavior and neuropathological sequelae. PMID:26537106

  20. Sex differences in synaptic plasticity in stress-responsive brain regions following chronic variable stress.

    PubMed

    Carvalho-Netto, Eduardo F; Myers, Brent; Jones, Kenneth; Solomon, Matia B; Herman, James P

    2011-08-01

    Increased stress responsiveness is implicated in the etiology of mood and anxiety disorders, including depression and post-traumatic stress disorder. Additionally, stress-related affective disorders have a higher incidence in women than men. Chronic stress in rodents produces numerous neuromorphological changes in a variety of limbic brain regions. Here, we examined the sex-dependent differences in presynaptic innervation of the paraventricular nucleus of the hypothalamus (PVN), prefrontal cortex (PFC), bed nucleus of the stria terminalis (BST), and amygdala in response to chronic variable stress (CVS). Following 14 days of CVS, the presynaptic protein synaptophysin was assessed in male and female rats. Our results demonstrate that synaptophysin staining density was higher in females than males in all brain areas evaluated, indicating sex differences in the organization of presynaptic innervation. After CVS, the PVN, principal nucleus of the BST (BSTpr), and basolateral nucleus of the amygdala (BLA) displayed significantly reduced synaptophysin density in females but not males. Furthermore, males showed an increase in synaptophysin in the PVN after CVS, suggesting a sex difference in the modulation of presynaptic inputs to the PVN following chronic stress. Overall, these data suggest marked sex differences in PVN, BSTpr, and BLA presynaptic innervation as a consequence of chronic stress, which may be associated with differential stress responsivity and perhaps susceptibility to pathologies in males and females. PMID:21315096

  1. Can Electrical Vestibular Noise Be Used for the Treatment of Brain Diseases?

    NASA Astrophysics Data System (ADS)

    Yamamoto, Yoshiharu; Soma, Rika; Struzik, Zbigniew R.; Kwak, Shin

    2005-11-01

    The therapy currently available for the treatment of degenerative neurological diseases is far from satisfactory, and a novel therapeutic strategy, especially for pharmacologically unresponsive patients, would be welcomed. The vestibular nerves are known to influence neuronal circuits in the medullary cardiovascular areas and, through the cerebellar vermis, the basal ganglia and the limbic system. By means of noisy galvanic vestibular stimulation (GVS), it may now be possible to ameliorate blunted responsiveness of degenerated neuronal circuits in the brains of multiple system atrophy (MSA) and/or Parkinson's disease (PD) patients, through a mechanism known as stochastic resonance. We evaluate the effect of 24-hour noisy GVS on long-term heart rate dynamics in seven MSA patients, and on daytime locomotor activity dynamics in twelve patients with either PD or levodopa unresponsive parkinsonism. Short-range heart rate variability and long-range anti-correlation of trunk activity are significantly increased by the noisy GVS compared with sham stimulation, suggestive of improved autonomic and motor responsiveness. The noisy GVS is effective in boosting the neuro-degenerative brains of MSA and/or PD patients, including those unresponsive to standard levodopa therapy.

  2. NMDA receptors regulate nicotine-enhanced brain reward function and intravenous nicotine self-administration: role of the ventral tegmental area and central nucleus of the amygdala.

    PubMed

    Kenny, Paul J; Chartoff, Elena; Roberto, Marisa; Carlezon, William A; Markou, Athina

    2009-01-01

    Nicotine is considered an important component of tobacco responsible for the smoking habit in humans. Nicotine increases glutamate-mediated transmission throughout brain reward circuitries. This action of nicotine could potentially contribute to its intrinsic rewarding and reward-enhancing properties, which motivate consumption of the drug. Here we show that the competitive N-methyl-D-aspartate (NMDA) receptor antagonist LY235959 (0.5-2.5 mg per kg) abolished nicotine-enhanced brain reward function, reflected in blockade of the lowering of intracranial self-stimulation (ICSS) thresholds usually observed after experimenter-administered (0.25 mg per kg) or intravenously self-administered (0.03 mg per kg per infusion) nicotine injections. The highest LY235959 dose (5 mg per kg) tested reversed the hedonic valence of nicotine from positive to negative, reflected in nicotine-induced elevations of ICSS thresholds. LY235959 doses that reversed nicotine-induced lowering of ICSS thresholds also markedly decreased nicotine self-administration without altering responding for food reinforcement, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonist NBQX had no effects on nicotine intake. In addition, nicotine self-administration upregulated NMDA receptor subunit expression in the central nucleus of the amygdala (CeA) and ventral tegmental area (VTA), suggesting important interactions between nicotine and the NMDA receptor. Furthermore, nicotine (1 microM) increased NMDA receptor-mediated excitatory postsynaptic currents in rat CeA slices, similar to its previously described effects in the VTA. Finally, infusion of LY235959 (0.1-10 ng per side) into the CeA or VTA decreased nicotine self-administration. Taken together, these data suggest that NMDA receptors, including those in the CeA and VTA, gate the magnitude and valence of the effects of nicotine on brain reward systems, thereby regulating motivation to consume the drug. PMID:18418357

  3. Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity.

    PubMed

    Malter, M P; Frisch, C; Schoene-Bake, J C; Helmstaedter, C; Wandinger, K P; Stoecker, W; Urbach, H; Surges, R; Elger, C E; Vincent, A V; Bien, C G

    2014-09-01

    In limbic encephalitis (LE) with antibodies (Abs) to the voltage-gated potassium channel complex (VGKC), the Abs are mainly directed to the VGKC-complex proteins, leucine-rich, glioma inactivated 1 protein (LGI1) or contactin-associated protein-like 2 (CASPR-2) or neither. Here, we relate the outcomes of VGKC-LE patients to the presence of Abs to LGI1, CASPR-2 or neither antigen (LGI1/CASPR-2-Ab(-)). Clinical, neuropsychology and MRI data were obtained from patient records for all LE patients from the Bonn Epilepsy Centre positive for VGKC-Abs by radioimmunoprecipitation assay between 2002 and 2011. Eighteen VGKC-LE patients were identified: nine patients (50 %) had LGI1-Abs, three (16 %) had CASPR-2-Abs; and six (33 %) were negative for both LGI1- and CASPR-2-Abs. At first assessment, the groups did not differ clinically or radiologically, but faciobrachial dystonic seizures were only observed in two LGI1-Ab(+) patients. All patients received monthly intravenous methylprednisolone (MP) pulses. At the most recent follow up (median 26 months), thirteen (72 %) were seizure-free, and seizure-freedom rates did not differ between the Ab groups. Hippocampal atrophy had developed in 7/9 LGI1-Ab(+) patients, but in none of the CASPR-2-Ab(+) or LGI/CASPR-2-Ab(-) patients (p = 0.003). While all subgroups improved, memory scores only normalized in six patients (33 %) and LGI1-Ab(+) patients were left with significantly poorer memory than the other two subgroups. Most VGKC-LE patients become seizure-free with pulsed monthly MP, but memory outcome is less favourable. Hippocampal atrophy and poor memory recovery is common in patients with LGI1-Abs and suggests permanent functional damage. More intense immunotherapies could improve outcomes in LGI1-Ab(+)-LE. PMID:24935858

  4. Ropinirole regulates emotionality and neuronal activity markers in the limbic forebrain.

    PubMed

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

    2014-12-01

    Restless legs syndrome (RLS) and Parkinson's disease (PD) are movement disorders usually accompanied by emotional and cognitive deficits. Although D3/D2 receptor agonists are effective against motor and non-motor deficits in RLS and PD, the exact behavioral and neurochemical effects of these drugs are not clearly defined. This study aimed to evaluate the effects of acute ropinirole (0, 0.1, 1 or 10 mg/kg, i.p.), a preferential D3/D2 receptor agonist, on intracranial self-stimulation (ICSS), spontaneous motor activity, anxiety- and depression-like behaviors, spatial reference and working memory in rats as well as on certain markers of neuronal activity, i.e. induction of immediate early genes, such as c-fos and arc, and crucial phosphorylations on GluA1 subunit of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and NA1, NA2A and NA2B subunits of N-methyl-D-aspartate (NMDA) receptors. Ropinirole decreased ICSS thresholds and induced anxiolytic- and antidepressive-like effects without affecting motor activity or spatial memory. The effects on emotionality were associated with a decrease in p-Ser897-NA1 and an increase in p-Tyr1472-NA2B in the ventral striatum as well as an increased induction of c-fos messenger RNA (mRNA) in the prefrontal cortex (PFC) and decreased expression of arc mRNA in the striatum and the shell of the nucleus accumbens. Our data indicate that ropinirole significantly affects emotionality at doses (1-10 mg/kg, i.p.) that exert no robust effects on locomotion or cognition. The data reinforce the use of D3/D2 receptor agonists in the treatment of RLS and PD patients characterized by emotional deficits and suggest that altered NMDA-mediated neurotransmission in the limbic forebrain may underlie some of ropinirole's therapeutic actions. PMID:24852388

  5. Trait anxiety modulates fronto-limbic processing of emotional interference in borderline personality disorder

    PubMed Central

    Holtmann, Jana; Herbort, Maike C.; Wüstenberg, Torsten; Soch, Joram; Richter, Sylvia; Walter, Henrik; Roepke, Stefan; Schott, Björn H.

    2013-01-01

    Previous studies of cognitive alterations in borderline personality disorder (BPD) have yielded conflicting results. Given that a core feature of BPD is affective instability, which is characterized by emotional hyperreactivity and deficits in emotion regulation, it seems conceivable that short-lasting emotional distress might exert temporary detrimental effects on cognitive performance. Here we used functional magnetic resonance imaging (fMRI) to investigate how task-irrelevant emotional stimuli (fearful faces) affect performance and fronto-limbic neural activity patterns during attention-demanding cognitive processing in 16 female, unmedicated BPD patients relative to 24 age-matched healthy controls. In a modified flanker task, emotionally negative, socially salient pictures (fearful vs. neutral faces) were presented as distracters in the background. Patients, but not controls, showed an atypical response pattern of the right amygdala with increased activation during emotional interference in the (difficult) incongruent flanker condition, but emotion-related amygdala deactivation in the congruent condition. A direct comparison of the emotional conditions between the two groups revealed that the strongest diagnosis-related differences could be observed in the dorsal and, to a lesser extent, also in the rostral anterior cingulate cortex (dACC, rACC) where patients exhibited an increased neural response to emotional relative to neutral distracters. Moreover, in the incongruent condition, both the dACC and rACC fMRI responses during emotional interference were negatively correlated with trait anxiety in the patients, but not in the healthy controls. As higher trait anxiety was also associated with longer reaction times (RTs) in the BPD patients, we suggest that in BPD patients the ACC might mediate compensatory cognitive processes during emotional interference and that such neurocognitive compensation that can be adversely affected by high levels of anxiety. PMID

  6. Trait anxiety modulates fronto-limbic processing of emotional interference in borderline personality disorder.

    PubMed

    Holtmann, Jana; Herbort, Maike C; Wüstenberg, Torsten; Soch, Joram; Richter, Sylvia; Walter, Henrik; Roepke, Stefan; Schott, Björn H

    2013-01-01

    Previous studies of cognitive alterations in borderline personality disorder (BPD) have yielded conflicting results. Given that a core feature of BPD is affective instability, which is characterized by emotional hyperreactivity and deficits in emotion regulation, it seems conceivable that short-lasting emotional distress might exert temporary detrimental effects on cognitive performance. Here we used functional magnetic resonance imaging (fMRI) to investigate how task-irrelevant emotional stimuli (fearful faces) affect performance and fronto-limbic neural activity patterns during attention-demanding cognitive processing in 16 female, unmedicated BPD patients relative to 24 age-matched healthy controls. In a modified flanker task, emotionally negative, socially salient pictures (fearful vs. neutral faces) were presented as distracters in the background. Patients, but not controls, showed an atypical response pattern of the right amygdala with increased activation during emotional interference in the (difficult) incongruent flanker condition, but emotion-related amygdala deactivation in the congruent condition. A direct comparison of the emotional conditions between the two groups revealed that the strongest diagnosis-related differences could be observed in the dorsal and, to a lesser extent, also in the rostral anterior cingulate cortex (dACC, rACC) where patients exhibited an increased neural response to emotional relative to neutral distracters. Moreover, in the incongruent condition, both the dACC and rACC fMRI responses during emotional interference were negatively correlated with trait anxiety in the patients, but not in the healthy controls. As higher trait anxiety was also associated with longer reaction times (RTs) in the BPD patients, we suggest that in BPD patients the ACC might mediate compensatory cognitive processes during emotional interference and that such neurocognitive compensation that can be adversely affected by high levels of anxiety. PMID

  7. Firing patterns of human limbic neurons during stereoencephalography (SEEG) and clinical temporal lobe seizures.

    PubMed

    Babb, T L; Wilson, C L; Isokawa-Akesson, M

    1987-06-01

    Comparisons of the patterns of neuronal firing and stereoencephalography (SEEG) recorded from the same microelectrodes chronically implanted in the human limbic system were made in order to study neuronal electrogenesis at onset and during propagation of focal partial complex seizures. Alert or sleeping patients were monitored during spontaneous subclinical seizures (no alterations in consciousness detectable), during auras reported by the patients as typical, and during clinical seizures with loss of consciousness, movements and post-ictal confusion. During subclinical SEEG seizures (ipsilateral, normal consciousness), few neurons increased firing (estimated at only 7%) either at the focus or at propagated sites. During auras, with altered consciousness, there were relatively few neurons that increased firing, with the estimate about 14% or twice as many as during a subclinical seizure. During the onset of a clinical seizure that involved loss of consciousness, movements and post-ictal confusion, many neurons were recruited into increased firing, with an estimate of approximately 36%. During this increased electrogenesis, neurons fired briefly in association with high-frequency local SEEG; however, the bursts were shorter than the SEEG seizure pattern. Apparently, other local neurons were recruited to fire in bursts to sustain sufficient axonal driving for widespread propagation of the seizure. When the focal SEEG slowed, the units stopped firing, which suggested that the 'focal' seizure need not be sustained for more than several seconds because propagated seizure activity was self-sustaining at distant structures. The data lead to the conclusion that SEEG seizures can be generated focally by synchronous firing of fewer than 10% of neurons in the 'epileptic pool.' However, when greater percentages of neurons are recruited in the 'epileptic focus' there is greater propagation to widespread sites, especially contralaterally, which will produce clinical partial

  8. GABAergic control of the ascending input from the median raphe nucleus to the limbic system.

    PubMed

    Li, Shaomin; Varga, Viktor; Sik, Attila; Kocsis, Bernat

    2005-10-01

    The median raphe nucleus (MRN) is the primary source of serotonergic afferents to the limbic system that are generally considered to suppress hippocampal theta oscillations. GABA receptors are expressed in the MRN by serotonergic and nonserotonergic cells, including GABAergic and glutamatergic neurons. This study investigated the mechanisms by which the fluctuating GABA tone in the MRN leads to induction or suppression of hippocampal theta rhythm. We found that MRN application of the GABA(A) agonist muscimol (0.05-1.0 mM) or GABA(B) agonist baclofen (0.2 mM) by reverse microdialysis had strong theta promoting effects. The GABA(A) antagonist bicuculline infused in low concentrations (0.1, 0.2 mM) eliminated theta rhythm. A short period of theta activity of higher than normal frequency preceded hippocampal desynchronization in 46% of rats. Bicuculline in larger concentrations (0.5, 1.0, 2.0 mM) resulted in a biphasic response of an initial short (<10 min) hippocampal desynchronization followed by stable theta rhythm that lasted as long as the infusion continued. The frequency and amplitude of theta waves were higher than in control recordings and the oscillations showed a conspicuous intermittent character. Hippocampal theta rhythm elicited by MRN administration of bicuculline could be completely (0.5 mM bicuculline) or partially (1.0 mM bicuculline) blocked by simultaneous infusion of the GABA(B) antagonist CGP35348. Our findings suggest that the GABAergic network may have two opposing functions in the MRN: relieving the theta-generators from serotonergic inhibition and regulating the activity of a theta-promoting circuitry by the fluctuating GABA tone. The two mechanisms may be involved in different functions. PMID:15944232

  9. Brain activity and connectivity during poetry composition: Toward a multidimensional model of the creative process

    PubMed Central

    Liu, Siyuan; Erkkinen, Michael G.; Healey, Meghan L.; Xu, Yisheng; Swett, Katherine E.; Chow, Ho Ming

    2015-01-01

    Abstract Creativity, a multifaceted construct, can be studied in various ways, for example, investigating phases of the creative process, quality of the creative product, or the impact of expertise. Previous neuroimaging studies have assessed these individually. Believing that each of these interacting features must be examined simultaneously to develop a comprehensive understanding of creative behavior, we examined poetry composition, assessing process, product, and expertise in a single experiment. Distinct activation patterns were associated with generation and revision, two major phases of the creative process. Medial prefrontal cortex (MPFC) was active during both phases, yet responses in dorsolateral prefrontal and parietal executive systems (DLPFC/IPS) were phase‐dependent, indicating that while motivation remains unchanged, cognitive control is attenuated during generation and re‐engaged during revision. Experts showed significantly stronger deactivation of DLPFC/IPS during generation, suggesting that they may more effectively suspend cognitive control. Importantly however, similar overall patterns were observed in both groups, indicating the same cognitive resources are available to experts and novices alike. Quality of poetry, assessed by an independent panel, was associated with divergent connectivity patterns in experts and novices, centered upon MPFC (for technical facility) and DLPFC/IPS (for innovation), suggesting a mechanism by which experts produce higher quality poetry. Crucially, each of these three key features can be understood in the context of a single neurocognitive model characterized by dynamic interactions between medial prefrontal areas regulating motivation, dorsolateral prefrontal, and parietal areas regulating cognitive control and the association of these regions with language, sensorimotor, limbic, and subcortical areas distributed throughout the brain. Hum Brain Mapp 36:3351–3372, 2015. © 2015 The Authors. Human Brain

  10. Film Excerpts Shown to Specifically Elicit Various Affects Lead to Overlapping Activation Foci in a Large Set of Symmetrical Brain Regions in Males

    PubMed Central

    Karama, Sherif; Armony, Jorge; Beauregard, Mario

    2011-01-01

    While the limbic system theory continues to be part of common scientific parlance, its validity has been questioned on multiple grounds. Nonetheless, the issue of whether or not there exists a set of brain areas preferentially dedicated to emotional processing remains central within affective neuroscience. Recently, a widespread neural reference space for emotion which includes limbic as well as other regions was characterized in a large meta-analysis. As methodologically heterogeneous studies go into such meta-analyses, showing in an individual study in which all parameters are kept constant, the involvement of overlapping areas for various emotion conditions in keeping with the neural reference space for emotion, would serve as valuable confirmatory evidence. Here, using fMRI, 20 young adult men were scanned while viewing validated neutral and effective emotion-eliciting short film excerpts shown to quickly and specifically elicit disgust, amusement, or sexual arousal. Each emotion-specific run included, in random order, multiple neutral and emotion condition blocks. A stringent conjunction analysis revealed a large overlap across emotion conditions that fit remarkably well with the neural reference space for emotion. This overlap included symmetrical bilateral activation of the medial prefrontal cortex, the anterior cingulate, the temporo-occipital junction, the basal ganglia, the brainstem, the amygdala, the hippocampus, the thalamus, the subthalamic nucleus, the posterior hypothalamus, the cerebellum, as well as the frontal operculum extending towards the anterior insula. This study clearly confirms for the visual modality, that processing emotional stimuli leads to widespread increases in activation that cluster within relatively confined areas, regardless of valence. PMID:21818311

  11. Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: Potential relevance of limbic GAD

    PubMed Central

    Ortiz, J. Bryce; Taylor, Sara B.; Hoffman, Ann N.; Campbell, Alyssa N.; Lucas, Louis R.; Conrad, Cheryl D.

    2015-01-01

    Chronic restraint stress alters hippocampal-dependent spatial learning and memory in a sex-dependent manner, impairing spatial performance in male rats and leaving intact or facilitating performance in female rats. Moreover, these stress-induced spatial memory deficits improve following post-stress recovery in males. The current study examined whether restraint administered in an unpredictable manner would eliminate these sex differences and impact a post-stress period on spatial ability and limbic glutamic acid decarboxylase (GAD65) expression. Male (n=30) and female (n=30) adult Sprague-Dawley rats were assigned to non-stressed control (Con), chronic stress (Str-Imm), or chronic stress given a post-stress recovery period (Str-Rec). Stressed rats were unpredictably restrained for 21 days using daily non-repeated combinations of physical context, duration, and time of day. Then, all rats were tested on the radial arm water maze (RAWM) for two days and given one retention trial on the third day, with brains removed 30 minutes later to assess GAD65 mRNA. In Str-Imm males, deficits occurred on day 1 of RAWM acquisition, an impairment that was not evident in the Str-Rec group. In contrast, females did not show significant outcomes following chronic stress or post-stress recovery. In males, amygdalar GAD65 expression negatively correlated with RAWM performance on day 1. In females, hippocampal CA1 GAD65 positively correlated with RAWM performance on day 1. These results demonstrate that GABAergic function may contribute to the sex differences observed following chronic stress. Furthermore, unpredictable restraint and a recovery period failed to eliminate the sex differences on spatial learning and memory. PMID:25591480

  12. Follistatin-like 5 is expressed in restricted areas of the adult mouse brain: Implications for its function in the olfactory system.

    PubMed

    Masuda, Tomoyuki; Sakuma, Chie; Nagaoka, Atsuko; Yamagishi, Toshiyuki; Ueda, Shuichi; Nagase, Takahiro; Yaginuma, Hiroyuki

    2014-02-01

    Follistatin-like 5 (Fstl5), a member of the follistatin family of genes, encodes a secretory glycoprotein. Previous studies revealed that other members of this family including Fstl1 and Fstl3 play an essential role in development, homeostasis, and congenital disorders. However, the in vivo function of Fstl5 is poorly understood. To gain insight into the function of Fstl5 in the mouse central nervous system, we examined the Fstl5 expression pattern in the adult mouse brain. The results of in situ hybridization analysis showed a highly restricted pattern of Fstl5, namely, with localization in the olfactory system, hippocampal CA3 area and granular cell layer of the cerebellum. Restricted expression in the olfactory system suggests a possible role for Fstl5 in maintaining odor perception. PMID:24588779

  13. Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring

    PubMed Central

    Hu, Min; Richard, Jennifer Elise; Maliqueo, Manuel; Kokosar, Milana; Fornes, Romina; Benrick, Anna; Jansson, Thomas; Ohlsson, Claes; Wu, Xiaoke; Skibicka, Karolina Patrycja; Stener-Victorin, Elisabet

    2015-01-01

    During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers. PMID:26578781

  14. Maternal testosterone exposure increases anxiety-like beha