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Sample records for attenuates limbic brain

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

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2010-07-01

    Full Text Available Dopamine (phasic release is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function was measured with PET and (18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg. The Cocaine-cues video increased craving to the same extent with placebo (68% and with methylphenidate (64%. In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005 in left limbic regions (insula, orbitofrontal, accumbens and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005, amygdala, striatum and middle insula (p<0.05. This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes, which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

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

    International Nuclear Information System (INIS)

    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.

    2010-01-01

    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 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

  3. Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

    OpenAIRE

    Volkow, Nora D.; Wang, Gene-Jack; Tomasi, Dardo; Telang, Frank; Fowler, Joanna S.; Pradhan, Kith; Jayne, Millard; Logan, Jean; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher

    2010-01-01

    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and...

  4. Oxytocin biotransformation in the rat limbic brain

    NARCIS (Netherlands)

    Burbach, J.P.H.; Schotman, P.; Kloet, E.R. de

    2006-01-01

    Two peptide fragments of oxytocin were isolated by high-pressure liquid chromatography from digests of oxytocin obtained after exposure to a SPM preparation of the rat limbic brain. The structures of these peptides, being Gln-Asn-Cys(O)x-Pro-Leu-GlyNH2 and Gln-Asn-Cys(-S-S-Cys)-Pro-Leu-GlyNH2, were

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anna R. Tröscher

    2017-10-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2010-10-28

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

  9. Escitalopram ameliorates hypercortisolemia and insulin resistance in low birth weight men with limbic brain alterations

    DEFF Research Database (Denmark)

    Buhl, Christian Selmer; Stødkilde-Jørgensen, Hans; Videbech, Poul

    2018-01-01

    CONTEXT: Low birth weight (LBW, insulin resistance and limbic-hypothalamic-pituitary-adrenal (LHPA)-axis hyperactivity. OBJECTIVE: First aim was to study insulin action, LHPA-axis function and limbic brain structures in young, healthy LBW-men vs. normal birth...... levels and improved Rdsubmax by ∼24% (p=0.04). CONCLUSIONS: LBW vs. NBW displayed alterations in key brain structures modulating LHPA-axis, elevated free cortisol levels and insulin resistance. Escitalopram administration ameliorated these defects, suggesting a potential for LHPA-axis modulation...... weight controls (NBW) (Part 1). Second aim was to investigate the effects of Escitalopram vs. placebo treatment in LBW with regards to LHPA-axis and insulin sensitivity (Part 2). DESIGN SETTING, PARTICIPANTS AND INTERVENTION: Maximal (Rdmax) and sub-maximal (Rdsubmax) rates of insulin-stimulated glucose...

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

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    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.

  11. Microstructure, length, and connection of limbic tracts in normal human brain development

    Directory of Open Access Journals (Sweden)

    Qiaowen eYu

    2014-08-01

    Full Text Available The cingulum and fornix play an important role in memory, attention, spatial orientation and feeling functions. Both microstructure and length of these limbic tracts can be affected by mental disorders such as Alzheimer’s disease, depression, autism, anxiety, and schizophrenia. To date, there has been little systematic characterization of their microstructure, length and functional connectivity in normally developing brains. In this study, diffusion tensor imaging (DTI and resting state functional MRI (rs-fMRI data from 65 normally developing right-handed subjects from birth to young adulthood was acquired. After cingulate gyrus part of the cingulum (cgc, hippocampal part of the cingulum (cgh and fornix (fx were traced with DTI tractography, absolute and normalized tract lengths and DTI-derived metrics including fractional anisotropy, mean, axial and radial diffusivity were measured for traced limbic tracts. Free water elimination (FWE algorithm was adopted to improve accuracy of the measurements of DTI-derived metrics. The role of these limbic tracts in the functional network at birth and adulthood was explored. We found a logarithmic age-dependent trajectory for FWE-corrected DTI metric changes with fast increase of microstructural integrity from birth to 2-year-old followed by a slow increase to 25-year-old. Normalized tract length of cgc increases with age, while no significant relationship with age was found for normalized tract lengths of cgh and fx. Stronger microstructural integrity on the left side compared to that of right side was found. With integrated DTI and rs-fMRI, the key connectional role of cgc and cgh in the default mode network (DMN was confirmed as early as birth. Systematic characterization of length and DTI metrics after FWE correction of limbic tracts offers insight into their morphological and microstructural developmental trajectories. These trajectories may serve as a normal reference for pediatric patients with

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

    Science.gov (United States)

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

    2017-09-01

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

  13. Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: a dosimetric study using helical tomotherapy

    International Nuclear Information System (INIS)

    Marsh, J.C.; Gielda, B.T.; Herskovic, A.M.; Turian, J.V.

    2010-01-01

    Full text: The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI). Methods and Materials: We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with VlOO ∼ 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V 100. Results: In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/ 14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean VlOO for the rest of the brain (PTV) were 94.7% (PCl) and 95.1 % (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27-17.5). Conclusions: It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose.

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

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    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

  15. Congenital olfactory impairment is linked to cortical changes in prefrontal and limbic brain regions

    DEFF Research Database (Denmark)

    Karstensen, Helena Gásdal; Vestergaard, Martin; Baaré, William F C

    2018-01-01

    differently in individuals who suffer from lifelong olfactory deprivation relative to healthy normosmic individuals. To address this question, we examined if regional variations in gray matter volume were associated with smell ability in seventeen individuals with isolated congenital olfactory impairment (COI...... in left middle frontal gyrus and right superior frontal sulcus (SFS). COI subjects with severe olfactory impairment (anosmia) had reduced grey matter volume in the left mOFC and increased volume in right piriform cortex and SFS. Within the COI group olfactory ability, measured with the "Sniffin' Sticks...... piriform cortex, while olfactory identification was negatively associated with right SFS volume. Our findings suggest that lifelong olfactory deprivation trigger changes in the cortical volume of prefrontal and limbic brain regions previously linked to olfactory memory....

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2018-05-01

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

  18. Chemosensory danger detection in the human brain: Body odor communicating aggression modulates limbic system activation.

    Science.gov (United States)

    Mutic, Smiljana; Brünner, Yvonne F; Rodriguez-Raecke, Rea; Wiesmann, Martin; Freiherr, Jessica

    2017-05-01

    Although the sense of smell is involved in numerous survival functions, the processing of body odor emitted by dangerous individuals is far from understood. The aim of the study was to explore how human fight chemosignals communicating aggression can alter brain activation related to an attentional bias and danger detection. While the anterior cingulate cortex (ACC) was seen involved in processing threat-related emotional information, danger detection and error evaluation, it still remains unknown whether human chemosignals communicating aggression can potentially modulate this activation. In the fMRI experiment, healthy male and female normosmic odor recipients (n=18) completed a higher-order processing task (emotional Stroop task with the word categories anger, anxiety, happiness and neutral) while exposed to aggression and exercise chemosignals (collected from a different group of healthy male donors; n=16). Our results provide first evidence that aggression chemosignals induce a time-sensitive attentional bias in chemosensory danger detection and modulate limbic system activation. During exposure to aggression chemosignals compared to exercise chemosignals, functional imaging data indicates an enhancement of thalamus, hypothalamus and insula activation (pbody odor signals are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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: pneurofeedback 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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-06-01

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

  1. Minocycline Attenuates Iron-Induced Brain Injury.

    Science.gov (United States)

    Zhao, Fan; Xi, Guohua; Liu, Wenqaun; Keep, Richard F; Hua, Ya

    2016-01-01

    Iron plays an important role in brain injury after intracerebral hemorrhage (ICH). Our previous study found minocycline reduces iron overload after ICH. The present study examined the effects of minocycline on the subacute brain injury induced by iron. Rats had an intracaudate injection of 50 μl of saline, iron, or iron + minocycline. All the animals were euthanized at day 3. Rat brains were used for immunohistochemistry (n = 5-6 per each group) and Western blotting assay (n = 4). Brain swelling, blood-brain barrier (BBB) disruption, and iron-handling proteins were measured. We found that intracerebral injection of iron resulted in brain swelling, BBB disruption, and brain iron-handling protein upregulation (p minocycline with iron significantly reduced iron-induced brain swelling (n = 5, p Minocycline significantly decreased albumin protein levels in the ipsilateral basal ganglia (p minocycline co-injected animals. In conclusion, the present study suggests that minocycline attenuates brain swelling and BBB disruption via an iron-chelation mechanism.

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

    Science.gov (United States)

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

    2013-01-01

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

  3. The effect of amperozide on uptake and release of [3H]-dopamine in vitro from perfused rat striatal and limbic brain areas

    International Nuclear Information System (INIS)

    Eriksson, E.; Christensson, E.

    1990-01-01

    Amperozide, a putatively antipsychotic drug, was studied for its effects on uptake and release of [ 3 H]-dopamine in rat brain in vitro. Amperozide inhibited uptake of [ 3 H]-dopamine in striatal chopped tissue in vitro with an IC 50 of 18 μM. It also increased basal release of [ 3 H]-dopamine from perfused rat striatal and limbic tissue in vitro at concentrations above 5 μM. Release of [ 3 H]-dopamine from perfused rat striatal and limbic tissue stimulated with 5 μM amphetamine, was inhibited by 1 μM amperozide to 46%. No significant difference was found for the effect of amperozide on in vitro release of [ 3 H]-dopamine from corpus striatum compared to tissue from limbic grain regions; neither on basal release nor on amphetamine-stimulated release of dopamine. (author)

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

    Science.gov (United States)

    Reyes, Beverly A S; Van Bockstaele, Elisabeth J

    2006-10-30

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

  5. The glucocorticoid receptor in the limbic system of the human brain

    NARCIS (Netherlands)

    Wang, Qian

    2016-01-01

    Glucocorticoid hormones (GCs) are important mediators of the stress response in mammals including humans. GCs are released from the adrenal in response to stress and affect numerous processes in the body and brain. Their levels are controlled via negative feedback exerted by GC binding to brain

  6. Leptin Receptor Deficiency is Associated With Upregulation of Cannabinoid 1 Receptors in Limbic Brain Regions

    Science.gov (United States)

    THANOS, PANAYOTIS K.; RAMALHETE, ROBERTO C.; MICHAELIDES, MICHAEL; PIYIS, YIANNI K.; WANG, GENE-JACK; VOLKOW, NORA D.

    2009-01-01

    Leptin receptor dysfunction results in overeating and obesity. Leptin regulates hypothalamic signaling that underlies the motivation to hyperphagia, but the interaction between leptin and cannabinoid signaling is poorly understood. We evaluated the role of cannabinoid 1 receptors (CB1R) in overeating and the effects of food deprivation on CB1R in the brain. One-month-old Zucker rats were divided into unrestricted and restricted (fed 70% of unrestricted rats) diet groups and maintained until adulthood (4 months). Levels of relative binding sites of CB1R (CB1R binding levels) were assessed using [3H] SR141716A in vitro autoradiography. These levels were higher (except cerebellum and hypothalamus) at 4 months than at 1 month of age. One month CB1R binding levels for most brain regions did not differ between Ob and Lean (Le) rats (except in frontal and cingulate cortices in Le and in the hypothalamus in Ob). Four month Ob rats had higher CB1R binding levels than Le in most brain regions and food restriction was associated with higher CB1R levels in all brain regions in Ob, but not in Le rats. CB1R binding levels increased between adolescence and young adulthood which we believe was influenced by leptin and food availability. The high levels of CB1R in Ob rats suggest that leptin's inhibition of food-intake is in part mediated by downregulation of CB1R and that leptin interferes with CB1R upregulation under food-deprivation conditions. These results are consistent with prior findings showing increased levels of endogenous cannabinoids in the Ob rats corroborating the regulation of cannabinoid signaling by leptin. PMID:18563836

  7. The development of the glucocorticoid receptor system in the rat limbic brain. 2

    International Nuclear Information System (INIS)

    Meaney, M.J.; Sapolsky, R.M.; McEwen, B.S.

    1985-01-01

    The authors report the results of an autoradiographic analysis of the postnatal development of the hippocampal glucocorticoid receptor system in the rat brain. Quantitative analysis of the autoradiograms revealed a varied pattern of gradual development towards adult receptor concentrations during the second week of life. Receptor concentrations in the dentate gyrus increased dramatically between Days 9 and 15, while the changes during this period in the pyramidal layers of Ammon's horn seemed to reflect both structural changes in these regions as well as increases in receptor concentrations. (orig.)

  8. 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

    Directory of Open Access Journals (Sweden)

    Joerg eBock

    2012-05-01

    Full Text Available 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 behaviour. 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, (D individual separation and presentation of maternal calls. Condition (B significantly downregulated brain activity in the prefrontal cortex, hippocampus, nucleus accumbens 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, nucleus accumbens and striatum and in sensory areas. In contrast, reduced activity was measured in the prelimbic and infralimbic cortex 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

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

    Directory of Open Access Journals (Sweden)

    Shaun M Eack

    Full Text Available 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.

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

    Science.gov (United States)

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

    2016-03-01

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

  11. Compensation for nonuniform attenuation in SPECT brain imaging

    International Nuclear Information System (INIS)

    Glick, S.J.; King, M.A.; Pan, T.S.; Soares, E.J.

    1996-01-01

    Accurate compensation for photon attenuation is needed to perform quantitative brain single-photon-emission computed tomographic (SPECT) imaging. Bellini's attenuation-compensation method has been used with a nonuniform attenuation map to account for the nonuniform attenuation properties of the head. Simulation studies using a three-dimensional (3-D) digitized anthropomorphic brain phantom were conducted to compare quantitative accuracy of reconstructions obtained with the nonuniform Bellini method to that obtained with the Chang method and to iterative reconstruction using maximum-likelihood expectation maximization (ML-EM). Using the Chang method and assuming the head to be a uniform attenuator gave reconstructions with an average bias of approximately 6-8%, whereas using the Bellini or the iterative ML-EM method with a nonuniform attenuation map gave an average bias of approximately 1%. The computation time required to implement nonuniform attenuation compensation with the Bellini algorithm is approximately equivalent to the time required to perform one iteration of ML-EM. Thus, using the Bellini method with a nonuniform attenuation map provides accurate compensation for photon attenuation within the head, and the method can be implemented in computation times suitable for routine clinical use

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

    Science.gov (United States)

    Walters, Glenn D; Kiehl, Kent A

    2015-12-15

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

  13. Compulsive Sexual Behavior: Prefrontal and Limbic Volume and Interactions

    DEFF Research Database (Denmark)

    Schmidt, Casper; Morris, Laurel S.; Kvamme, Timo L.

    2017-01-01

    prefrontal cortex (whole brain, cluster corrected FWE P motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions...

  14. Associations of limbic-affective brain activity and severity of ongoing chronic arthritis pain are explained by trait anxiety

    Directory of Open Access Journals (Sweden)

    William J. Cottam

    2016-01-01

    Full Text Available Functional magnetic resonance imaging studies (fMRI have transformed our understanding of central processing of evoked pain but the typically used block and event-related designs are not best suited to the study of ongoing pain. Here we used arterial spin labelling (ASL for cerebral blood flow mapping to characterise the neural correlates of perceived intensity of osteoarthritis (OA pain and its interrelation with negative affect. Twenty-six patients with painful knee OA and twenty-seven healthy controls underwent pain phenotyping and ASL MRI at 3T. Intensity of OA pain correlated positively with blood flow in the anterior mid-cingulate cortex (aMCC, subgenual cingulate cortex (sgACC, bilateral hippocampi, bilateral amygdala, left central operculum, mid-insula, putamen and the brainstem. Additional control for trait anxiety scores reduced the pain-CBF association to the aMCC, whilst pain catastrophizing scores only explained some of the limbic correlations. In conclusion, we found that neural correlates of reported intensity of ongoing chronic pain intensity mapped to limbic-affective circuits, and that the association pattern apart from aMCC was explained by trait anxiety thus highlighting the importance of aversiveness in the experience of clinical pain.

  15. Neonatal domoic acid increases receptor density of α2 adrenoceptors and GABAA α5 receptors in limbic brain regions of adult rats

    DEFF Research Database (Denmark)

    Thomsen, Majken; Lillethorup, Thea Pinholt; Wegener, Gregers

    Background: The presymptomatic events involved in neurological disorders such as epilepsy remain elusive but represent an opportunity to understand disease development and stop the pathogenic processes leading to chronic epilepsy. Previous studies using Western blot and immunohistochemistry have...... found increased levels of α2 adrenoceptors in the hippocampal membrane of adult rats treated neonatally with low-dose domoic acid (DOM) along with decreased levels of both isoforms of glutamic acid decarboxylase (GAD), a catalyst of the decarboxylation of glutamate to GABA, indicating a reduction...... in GABAergic interneurons. Objectives: The aim of the present study was to investigate the expression of GABAA α5 and α2 adrenoceptors in limbic brain regions in a DOM rat model of epilepsy using autoradiography. Methods: Male Sprague-Dawley rats (N=3) were injected (s.c.) daily from postnatal day 8...

  16. Anti-Ma2 antibody related paraneoplastic limbic/brain stem encephalitis associated with breast cancer expressing Ma1, Ma2, and Ma3 mRNAs.

    Science.gov (United States)

    Sahashi, K; Sakai, K; Mano, K; Hirose, G

    2003-09-01

    A 69 year old woman presented with cognitive impairment and supranuclear gaze palsy caused by paraneoplastic limbic/brain stem encephalitis associated with atypical medullary breast carcinoma. The cerebrospinal fluid from the patient harboured an anti-neuronal cell antibody against Ma2 antigen, but not against Ma1 or Ma3 antigen. Despite the antibody being restricted to the Ma2 antigen, the patient's cancer tissue expressed Ma1, Ma2, and Ma3 mRNAs. These results, and the expression of Ma2 mRNA in an atypical medullar breast carcinoma in another patient without paraneoplastic encephalitis, indicate that the induction of anti-Ma2 antibody depends on host immunoreponsiveness and not on the presence of the antigen itself in the cancer.

  17. Quantitative SPECT brain imaging: Effects of attenuation and detector response

    International Nuclear Information System (INIS)

    Gilland, D.R.; Jaszczak, R.J.; Bowsher, J.E.; Turkington, T.G.; Liang, Z.; Greer, K.L.; Coleman, R.E.

    1993-01-01

    Two physical factors that substantially degrade quantitative accuracy in SPECT imaging of the brain are attenuation and detector response. In addition to the physical factors, random noise in the reconstructed image can greatly affect the quantitative measurement. The purpose of this work was to implement two reconstruction methods that compensate for attenuation and detector response, a 3D maximum likelihood-EM method (ML) and a filtered backprojection method (FB) with Metz filter and Chang attenuation compensation, and compare the methods in terms of quantitative accuracy and image noise. The methods were tested on simulated data of the 3D Hoffman brain phantom. The simulation incorporated attenuation and distance-dependent detector response. Bias and standard deviation of reconstructed voxel intensities were measured in the gray and white matter regions. The results with ML showed that in both the gray and white matter regions as the number of iterations increased, bias decreased and standard deviation increased. Similar results were observed with FB as the Metz filter power increased. In both regions, ML had smaller standard deviation than FB for a given bias. Reconstruction times for the ML method have been greatly reduced through efficient coding, limited source support, and by computing attenuation factors only along rays perpendicular to the detector

  18. Is Necessary Attenuation Correction for Cat Brain PET?

    International Nuclear Information System (INIS)

    Kim, Jin Su; Lee, Jae Sung; Park, Min Hyun; Im, Ki Chun; Oh, Seung Ha; Lee, Dong Soo; Moon, Dae Hyuk

    2007-01-01

    Photon attenuation and scatter corrections (AC and SC) were necessary for quantification of human PET. However, there is no consensus on whether AC and SC are necessary for the cat brain PET imaging. Since post-injection transmission (TX) PET scans are not permitted or provided to microPET scanner users at present, additional time for performing TX scan and awaiting FDG uptake is required for attenuation and scatter corrections. Increasing probability of subject movement and possible biological effect of long term anesthesia would be the problem in additional TX scan. The aim of this study was to examine the effect of AC and SC for the quantification of cat brain PET data

  19. [Limbic encephalitis with antibodies against intracellular antigens].

    Science.gov (United States)

    Morita, Akihiko; Kamei, Satoshi

    2010-04-01

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

  20. Differences in frontal and limbic brain activation in a small sample of monozygotic twin pairs discordant for severe stressful life events

    Directory of Open Access Journals (Sweden)

    Detre A. Godinez

    2016-12-01

    Full Text Available Monozygotic twin pairs provide a valuable opportunity to control for genetic and shared environmental influences while studying the effects of nonshared environmental influences. The question we address with this design is whether monozygotic twins selected for discordance in exposure to severe stressful life events during development (before age 18 demonstrate differences in brain activation during performance of an emotional word-face Stroop task. In this study, functional magnetic resonance imaging was used to assess brain activation in eighteen young adult twins who were discordant in exposure to severe stress such that one twin had two or more severe events compared to their control co-twin who had no severe events. Twins who experienced higher levels of stress during development, compared to their control co-twins with lower stress, exhibited significant clusters of greater activation in the ventrolateral and medial prefrontal cortex, basal ganglia, and limbic regions. The control co-twins showed only the more typical recruitment of frontoparietal regions thought to be important for executive control of attention and maintenance of task goals. Behavioral performance was not significantly different between twins within pairs, suggesting the twins with stress recruited additional neural resources associated with affective processing and updating working memory when performing at the same level. This study provides a powerful glimpse at the potential effects of stress during development while accounting for shared genetic and environmental influences.

  1. Systemic injection of kainic acid: Gliosis in olfactory and limbic brain regions quantified with [3H]PK 11195 binding autoradiography

    International Nuclear Information System (INIS)

    Altar, C.A.; Baudry, M.

    1990-01-01

    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

  2. Acute stress evokes sexually dimorphic, stressor-specific patterns of neural activation across multiple limbic brain regions in adult rats.

    Science.gov (United States)

    Sood, Ankit; Chaudhari, Karina; Vaidya, Vidita A

    2018-03-01

    Stress enhances the risk for psychiatric disorders such as anxiety and depression. Stress responses vary across sex and may underlie the heightened vulnerability to psychopathology in females. Here, we examined the influence of acute immobilization stress (AIS) and a two-day short-term forced swim stress (FS) on neural activation in multiple cortical and subcortical brain regions, implicated as targets of stress and in the regulation of neuroendocrine stress responses, in male and female rats using Fos as a neural activity marker. AIS evoked a sex-dependent pattern of neural activation within the cingulate and infralimbic subdivisions of the medial prefrontal cortex (mPFC), lateral septum (LS), habenula, and hippocampal subfields. The degree of neural activation in the mPFC, LS, and habenula was higher in males. Female rats exhibited reduced Fos positive cell numbers in the dentate gyrus hippocampal subfield, an effect not observed in males. We addressed whether the sexually dimorphic neural activation pattern noted following AIS was also observed with the short-term stress of FS. In the paraventricular nucleus of the hypothalamus and the amygdala, FS similar to AIS resulted in robust increases in neural activation in both sexes. The pattern of neural activation evoked by FS was distinct across sexes, with a heightened neural activation noted in the prelimbic mPFC subdivision and hippocampal subfields in females and differed from the pattern noted with AIS. This indicates that the sex differences in neural activation patterns observed within stress-responsive brain regions are dependent on the nature of stressor experience.

  3. Limbic Irritability, Neuronal Complexity and Smoking

    Czech Academy of Sciences Publication Activity Database

    Svetlak, M.; Bob, P.; Černík, M.; Konečný, P.; Chládek, Jan; Svrček, M.; Kukleta, M.

    2008-01-01

    Roč. 50, č. 3 (2008), s. 85 ISSN 0001-7604. [International CIANS Conference 2008: Higher Brain Functions. 28.09.2008-02.10.2008, Smolenice] Institutional research plan: CEZ:AV0Z20650511 Keywords : smoking * limbic irritability * stress * complexity * EDA Subject RIV: FH - Neurology

  4. MR constrained simultaneous reconstruction of activity and attenuation maps in brain TOF-PET/MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mehranian, Abolfazl; Zaidi, Habib [Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland)

    2014-07-29

    The maximum likelihood estimation of attenuation and activity (MLAA) algorithm has been proposed to jointly estimate activity and attenuation from emission data only. Salomon et al employed the MLAA to estimate activity and attenuation from time-of-flight PET data with spatial MR prior information on attenuation. Recently, we proposed a novel algorithm to impose both spatial and statistical constraints on attenuation estimation within the MLAA algorithm using Dixon MR images and a constrained Gaussian mixture model (GMM). In this study, we compare the proposed algorithm with MLAA and MLAA-Salomon in brain TOF-PET/MR imaging.

  5. MR constrained simultaneous reconstruction of activity and attenuation maps in brain TOF-PET/MR imaging

    International Nuclear Information System (INIS)

    Mehranian, Abolfazl; Zaidi, Habib

    2014-01-01

    The maximum likelihood estimation of attenuation and activity (MLAA) algorithm has been proposed to jointly estimate activity and attenuation from emission data only. Salomon et al employed the MLAA to estimate activity and attenuation from time-of-flight PET data with spatial MR prior information on attenuation. Recently, we proposed a novel algorithm to impose both spatial and statistical constraints on attenuation estimation within the MLAA algorithm using Dixon MR images and a constrained Gaussian mixture model (GMM). In this study, we compare the proposed algorithm with MLAA and MLAA_Salomon in brain TOF-PET/MR imaging.

  6. Integral dose delivered to normal brain with conventional intensity-modulated radiotherapy (IMRT) and helical tomotherapy IMRT during partial brain radiotherapy for high-grade gliomas with and without selective sparing of the hippocampus, limbic circuit and neural stem cell compartment

    International Nuclear Information System (INIS)

    Marsh, James C.; Ziel, Ellis G; Diaz, Aidnag Z; Turian, Julius V; Wendt, Julie A.; Gobole, Rohit

    2013-01-01

    We compared integral dose with uninvolved brain (ID brain ) during partial brain radiotherapy (PBRT) for high-grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse-planned intensity-modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit. We prepared four PBRT treatment plans for four patients with high-grade gliomas (60Gy in 30 fractions delivered to planning treatment volume (PTV60Gy)). For all plans, a structure denoted 'uninvolved brain' was created, which included all brain tissue not part of PTV or standard (STD) organs at risk (OAR). No dosimetric constraints were included for uninvolved brain. Selective SPA plans were prepared with IMRT and HT; contralateral hippocampus, NSC and limbic circuit were contoured; and dosimetric constraints were entered for these structures without compromising dose to PTV or STD OAR. We compared V100 and D95 for PTV46Gy and PTV60Gy, and ID brain for all plans. There were no significant differences in V100 and D95 for PTV46Gy and PTV60Gy. ID brain was lower in traditional IMRT versus HT plans for STD and SPA plans (mean ID brain 23.64Gy vs. 28Gy and 18.7Gy vs. 24.5Gy, respectively) and in SPA versus STD plans both with IMRT and HT (18.7Gy vs. 23.64Gy and 24.5Gy vs. 28Gy, respectively). n the setting of PBRT for high-grade gliomas, IMRT reduces ID brain compared with HT with or without selective SPA of contralateral hippocampus, limbic circuit and NSC, and the use of selective SPA reduces ID brain compared with STD PBRT delivered with either traditional IMRT or HT.

  7. Hyper-attenuating brain lesions on CT after ischemic stroke and thrombectomy are associated with final brain infarction.

    Science.gov (United States)

    Cabral, F B; Castro-Afonso, L H; Nakiri, G S; Monsignore, L M; Fábio, Src; Dos Santos, A C; Pontes-Neto, O M; Abud, D G

    2017-12-01

    Purpose Hyper-attenuating lesions, or contrast staining, on a non-contrast brain computed tomography (NCCT) scan have been investigated as a predictor for hemorrhagic transformation after endovascular treatment of acute ischemic stroke (AIS). However, the association of hyper-attenuating lesions and final ischemic areas are poorly investigated in this setting. The aim of the present study was to assess correlations between hyper-attenuating lesions and final brain infarcted areas after thrombectomy for AIS. Methods Data from patients with AIS of the anterior circulation who underwent endovascular treatment were retrospectively assessed. Images of the brain NCCT scans were analyzed in the first hours and late after treatment. The hyper-attenuating areas were compared to the final ischemic areas using the Alberta Stroke Program Early CT Score (ASPECTS). Results Seventy-one of the 123 patients (65.13%) treated were included. The association between the hyper-attenuating region in the post-thrombectomy CT scan and final brain ischemic area were sensitivity (58.3% to 96.9%), specificity (42.9% to 95.6%), positive predictive values (71.4% to 97.7%), negative predictive values (53.8% to 79.5%), and accuracy values (68% to 91%). The highest sensitivity values were found for the lentiform (96.9%) and caudate nuclei (80.4%) and for the internal capsule (87.5%), and the lowest values were found for the M1 (58.3%) and M6 (66.7%) cortices. Conclusions Hyper-attenuating lesions on head NCCT scans performed after endovascular treatment of AIS may predict final brain infarcted areas. The prediction appears to be higher in the deep brain regions compared with the cortical regions.

  8. Attenuation correction for the large non-human primate brain imaging using microPET

    International Nuclear Information System (INIS)

    Naidoo-Variawa, S; Lehnert, W; Kassiou, M; Banati, R; Meikle, S R

    2010-01-01

    Assessment of the biodistribution and pharmacokinetics of radiopharmaceuticals in vivo is often performed on animal models of human disease prior to their use in humans. The baboon brain is physiologically and neuro-anatomically similar to the human brain and is therefore a suitable model for evaluating novel CNS radioligands. We previously demonstrated the feasibility of performing baboon brain imaging on a dedicated small animal PET scanner provided that the data are accurately corrected for degrading physical effects such as photon attenuation in the body. In this study, we investigated factors affecting the accuracy and reliability of alternative attenuation correction strategies when imaging the brain of a large non-human primate (papio hamadryas) using the microPET Focus 220 animal scanner. For measured attenuation correction, the best bias versus noise performance was achieved using a 57 Co transmission point source with a 4% energy window. The optimal energy window for a 68 Ge transmission source operating in singles acquisition mode was 20%, independent of the source strength, providing bias-noise performance almost as good as for 57 Co. For both transmission sources, doubling the acquisition time had minimal impact on the bias-noise trade-off for corrected emission images, despite observable improvements in reconstructed attenuation values. In a [ 18 F]FDG brain scan of a female baboon, both measured attenuation correction strategies achieved good results and similar SNR, while segmented attenuation correction (based on uncorrected emission images) resulted in appreciable regional bias in deep grey matter structures and the skull. We conclude that measured attenuation correction using a single pass 57 Co (4% energy window) or 68 Ge (20% window) transmission scan achieves an excellent trade-off between bias and propagation of noise when imaging the large non-human primate brain with a microPET scanner.

  9. Errors in MR-based attenuation correction for brain imaging with PET/MR scanners

    International Nuclear Information System (INIS)

    Rota Kops, Elena; Herzog, Hans

    2013-01-01

    Aim: Attenuation correction of PET data acquired by hybrid MR/PET scanners remains a challenge, even if several methods for brain and whole-body measurements have been developed recently. A template-based attenuation correction for brain imaging proposed by our group is easy to handle and delivers reliable attenuation maps in a short time. However, some potential error sources are analyzed in this study. We investigated the choice of template reference head among all the available data (error A), and possible skull anomalies of the specific patient, such as discontinuities due to surgery (error B). Materials and methods: An anatomical MR measurement and a 2-bed-position transmission scan covering the whole head and neck region were performed in eight normal subjects (4 females, 4 males). Error A: Taking alternatively one of the eight heads as reference, eight different templates were created by nonlinearly registering the images to the reference and calculating the average. Eight patients (4 females, 4 males; 4 with brain lesions, 4 w/o brain lesions) were measured in the Siemens BrainPET/MR scanner. The eight templates were used to generate the patients' attenuation maps required for reconstruction. ROI and VOI atlas-based comparisons were performed employing all the reconstructed images. Error B: CT-based attenuation maps of two volunteers were manipulated by manually inserting several skull lesions and filling a nasal cavity. The corresponding attenuation coefficients were substituted with the water's coefficient (0.096/cm). Results: Error A: The mean SUVs over the eight templates pairs for all eight patients and all VOIs did not differ significantly one from each other. Standard deviations up to 1.24% were found. Error B: After reconstruction of the volunteers' BrainPET data with the CT-based attenuation maps without and with skull anomalies, a VOI-atlas analysis was performed revealing very little influence of the skull lesions (less than 3%), while the filled

  10. Errors in MR-based attenuation correction for brain imaging with PET/MR scanners

    Science.gov (United States)

    Rota Kops, Elena; Herzog, Hans

    2013-02-01

    AimAttenuation correction of PET data acquired by hybrid MR/PET scanners remains a challenge, even if several methods for brain and whole-body measurements have been developed recently. A template-based attenuation correction for brain imaging proposed by our group is easy to handle and delivers reliable attenuation maps in a short time. However, some potential error sources are analyzed in this study. We investigated the choice of template reference head among all the available data (error A), and possible skull anomalies of the specific patient, such as discontinuities due to surgery (error B). Materials and methodsAn anatomical MR measurement and a 2-bed-position transmission scan covering the whole head and neck region were performed in eight normal subjects (4 females, 4 males). Error A: Taking alternatively one of the eight heads as reference, eight different templates were created by nonlinearly registering the images to the reference and calculating the average. Eight patients (4 females, 4 males; 4 with brain lesions, 4 w/o brain lesions) were measured in the Siemens BrainPET/MR scanner. The eight templates were used to generate the patients' attenuation maps required for reconstruction. ROI and VOI atlas-based comparisons were performed employing all the reconstructed images. Error B: CT-based attenuation maps of two volunteers were manipulated by manually inserting several skull lesions and filling a nasal cavity. The corresponding attenuation coefficients were substituted with the water's coefficient (0.096/cm). ResultsError A: The mean SUVs over the eight templates pairs for all eight patients and all VOIs did not differ significantly one from each other. Standard deviations up to 1.24% were found. Error B: After reconstruction of the volunteers' BrainPET data with the CT-based attenuation maps without and with skull anomalies, a VOI-atlas analysis was performed revealing very little influence of the skull lesions (less than 3%), while the filled nasal

  11. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

    Directory of Open Access Journals (Sweden)

    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  12. Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia

    Science.gov (United States)

    Kim, Jae Hwan; Lee, Yong Woo; Park, Kyung Ah; Lee, Won Taek; Lee, Jong Eun

    2010-01-01

    Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of -arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Results showed that agmatine significantly reduced brain swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water content in brain tissue was clearly decreased 24 h after ischemic injury by agmatine treatment. Blood–brain barrier (BBB) disruption was diminished with agmatine than without. The expressions of AQPs-1 and -9 were well correlated with brain edema as water channels, were significantly decreased by agmatine treatment. It can thus be suggested that agmatine could attenuate brain edema by limitting BBB disruption and blocking the accumulation of brain water content through lessening the expression of AQP-1 after cerebral ischemia. PMID:20029450

  13. Attenuation correction for freely moving small animal brain PET studies based on a virtual scanner geometry

    International Nuclear Information System (INIS)

    Angelis, G I; Kyme, A Z; Ryder, W J; Fulton, R R; Meikle, S R

    2014-01-01

    Attenuation correction in positron emission tomography brain imaging of freely moving animals is a very challenging problem since the torso of the animal is often within the field of view and introduces a non negligible attenuating factor that can degrade the quantitative accuracy of the reconstructed images. In the context of unrestrained small animal imaging, estimation of the attenuation correction factors without the need for a transmission scan is highly desirable. An attractive approach that avoids the need for a transmission scan involves the generation of the hull of the animal’s head based on the reconstructed motion corrected emission images. However, this approach ignores the attenuation introduced by the animal’s torso. In this work, we propose a virtual scanner geometry which moves in synchrony with the animal’s head and discriminates between those events that traversed only the animal’s head (and therefore can be accurately compensated for attenuation) and those that might have also traversed the animal’s torso. For each recorded pose of the animal’s head a new virtual scanner geometry is defined and therefore a new system matrix must be calculated leading to a time-varying system matrix. This new approach was evaluated on phantom data acquired on the microPET Focus 220 scanner using a custom-made phantom and step-wise motion. Results showed that when the animal’s torso is within the FOV and not appropriately accounted for during attenuation correction it can lead to bias of up to 10% . Attenuation correction was more accurate when the virtual scanner was employed leading to improved quantitative estimates (bias < 2%), without the need to account for the attenuation introduced by the extraneous compartment. Although the proposed method requires increased computational resources, it can provide a reliable approach towards quantitatively accurate attenuation correction for freely moving animal studies. (paper)

  14. Limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies as a cause of adult-onset mesial temporal lobe epilepsy.

    Science.gov (United States)

    Toyota, Tomoko; Akamatsu, Naoki; Tsuji, Sadatoshi; Nishizawa, Shigeru

    2014-06-01

    Recently, some reports have indicated that limbic encephalitis associated with anti-voltage-gated potassium channel complex antibodies (VGKC-Ab) is a cause of adult-onset mesial temporal lobe epilepsy (MTLE). We report a 53-year-old woman who had her first epileptic seizure at the age of 50 years old. Examination by 3-Tesla brain MRI revealed left hippocampal high signal intensity and swelling on fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging at 2 months after her first seizure. The patient received intravenous methylprednisolone and carbamazepine 300 mg/day. One month later, MRI revealed improvement of her left hippocampal abnormalities. Thereafter, she had no seizures, however, three years after her first seizure, EEG revealed a seizure pattern in the left temporal region. Brain MRI revealed left hippocampal high signal intensity and brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism. Her serum VGKC-Ab levels were 118 pM(normal VGKC-Ab levels decreased to 4.4 pM. Remission of the epileptic seizures was also observed. This MTLE in the middle age was considered as limbic encephalitis associated with anti- VGKC-Ab. In cases of unexplained adult-onset MTLE, limbic encephalitis associated with anti-VGKC-Ab, which responds well to immunotherapy, should be considered in the differential diagnosis.

  15. Quantitative SPECT reconstruction for brain distribution with a non-uniform attenuation using a regularizing method

    International Nuclear Information System (INIS)

    Soussaline, F.; Bidaut, L.; Raynaud, C.; Le Coq, G.

    1983-06-01

    An analytical solution to the SPECT reconstruction problem, where the actual attenuation effect can be included, was developped using a regularizing iterative method (RIM). The potential of this approach in quantitative brain studies when using a tracer for cerebrovascular disorders is now under evaluation. Mathematical simulations for a distributed activity in the brain surrounded by the skull and physical phantom studies were performed, using a rotating camera based SPECT system, allowing the calibration of the system and the evaluation of the adapted method to be used. On the simulation studies, the contrast obtained along a profile, was less than 5%, the standard deviation 8% and the quantitative accuracy 13%, for a uniform emission distribution of mean = 100 per pixel and a double attenuation coefficient of μ = 0.115 cm -1 and 0.5 cm -1 . Clinical data obtained after injection of 123 I (AMPI) were reconstructed using the RIM without and with cerebrovascular diseases or lesion defects. Contour finding techniques were used for the delineation of the brain and the skull, and measured attenuation coefficients were assumed within these two regions. Using volumes of interest, selected on homogeneous regions on an hemisphere and reported symetrically, the statistical uncertainty for 300 K events in the tomogram was found to be 12%, the index of symetry was of 4% for normal distribution. These results suggest that quantitative SPECT reconstruction for brain distribution is feasible, and that combined with an adapted tracer and an adequate model physiopathological parameters could be extracted

  16. Role of the limbic system in dependence on drugs.

    Science.gov (United States)

    Rodríguez de Fonseca, F; Navarro, M

    1998-08-01

    The limbic system is a group of structurally and functionally related areas of the brain that provides the anatomical substrate for emotions and motivated behaviour, including the circuitry for the stress response and reward-related events. This system is strongly implicated in drug abuse from the pleasure and/or positive side associated with acute exposure to the dysphoria and craving associated with withdrawal. The contribution of the main cortical and subcortical elements of the limbic system to drug dependence is briefly reviewed in the present work with a focus on the role of the extended amygdala and its connections as well as on the peripheral feedback signals mediated by adrenal glucocorticoids. The elucidation of the neuroadaptive responses of the limbic system to chronic drug exposure will undoubtedly help to design rational strategies for the treatment of addiction.

  17. Opposite effect of phencyclidine on activity-regulated cytoskeleton-associated protein (Arc) in juvenile and adult limbic rat brain regions

    DEFF Research Database (Denmark)

    Thomsen, Morten S; Hansen, Henrik H; Mikkelsen, Jens D

    2010-01-01

    -regulated cytoskeleton-associated protein (Arc) and parvalbumin mRNA expression in juvenile and adult rats. Arc is a marker for excitatory neurotransmission. Parvalbumin is a marker for GABAergic neurotransmission, known to be reduced in postmortem brains of schizophrenics. PCP reduced parvalbumin mRNA expression...

  18. Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.

    Science.gov (United States)

    Cheng, Zhuo; Wang, Liping; Qu, Meijie; Liang, Huaibin; Li, Wanlu; Li, Yongfang; Deng, Lidong; Zhang, Zhijun; Yang, Guo-Yuan

    2018-05-03

    Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 10 5 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p mesenchymal stem cell-treated mice compared to the control group following ischemia (p cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.

  19. Prostate cancer may trigger paraneoplastic limbic encephalitis

    DEFF Research Database (Denmark)

    Jakobsen, Jakob Kristian; Zakharia, Elias Raja; Boysen, Anders Kindberg Fossø

    2013-01-01

    -Hu antibody test the patient was diagnosed with paraneoplastic limbic encephalitis related to prostate cancer. The patient died within 6 months. We review the literature on prostate cancer-related paraneoplastic limbic encephalitis. High-risk prostate cancer can trigger paraneoplastic limbic encephalitis...

  20. Increased receptor density of α2 adrenoceptors and GABAA α5 receptors in limbic brain regions in the domoic acid rat model of epilepsy

    DEFF Research Database (Denmark)

    Thomsen, Majken; Lillethorup, Thea Pinholt; Wegener, Gregers

    Background: The presymptomatic events involved in epilepsy remain elusive but represent a chance to understand disease development and stop the pathogenic processes leading to chronic epilepsy. Previous studies have found increased levels of α2 adrenoceptors and decreased levels of glutamic acid...... decarboxylase, a catalyst of the decarboxylation of glutamate to GABA. Methods: Male Sprague-Dawley rats (N=3) were injected (s.c.) daily from postnatal day 8-14 with saline or sub-convulsive doses of the glutamate agonist DOM (20µg/kg). At ~120 days of age the rats were decapitated. The brains were removed...

  1. Fuel not fun: Reinterpreting attenuated brain responses to reward in obesity.

    Science.gov (United States)

    Kroemer, Nils B; Small, Dana M

    2016-08-01

    There is a well-established literature linking obesity to altered dopamine signaling and brain response to food-related stimuli. Neuroimaging studies frequently report enhanced responses in dopaminergic regions during food anticipation and decreased responses during reward receipt. This has been interpreted as reflecting anticipatory "reward surfeit", and consummatory "reward deficiency". In particular, attenuated response in the dorsal striatum to primary food rewards is proposed to reflect anhedonia, which leads to overeating in an attempt to compensate for the reward deficit. In this paper, we propose an alternative view. We consider brain response to food-related stimuli in a reinforcement-learning framework, which can be employed to separate the contributions of reward sensitivity and reward-related learning that are typically entangled in the brain response to reward. Consequently, we posit that decreased striatal responses to milkshake receipt reflect reduced reward-related learning rather than reward deficiency or anhedonia because reduced reward sensitivity would translate uniformly into reduced anticipatory and consummatory responses to reward. By re-conceptualizing reward deficiency as a shift in learning about subjective value of rewards, we attempt to reconcile neuroimaging findings with the putative role of dopamine in effort, energy expenditure and exploration and suggest that attenuated brain responses to energy dense foods reflect the "fuel", not the fun entailed by the reward. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Non-uniform versus uniform attenuation correction in brain perfusion SPET of healthy volunteers

    International Nuclear Information System (INIS)

    Van Laere, K.; Versijpt, J.; Dierckx, R.; Koole, M.

    2001-01-01

    Although non-uniform attenuation correction (NUAC) can supply more accurate absolute quantification, it is not entirely clear whether NUAC provides clear-cut benefits in the routine clinical practice of brain SPET imaging. The aim of this study was to compare the effect of NUAC versus uniform attenuation correction (UAC) on volume of interest (VOI)-based semi-quantification of a large age- and gender-stratified brain perfusion normal database. Eighty-nine healthy volunteers (46 females and 43 males, aged 20-81 years) underwent standardised high-resolution single-photon emission tomography (SPET) with 925 MBq 99m Tc-ethyl cysteinate dimer (ECD) on a Toshiba GCA-9300A camera with 153 Gd or 99m Tc transmission CT scanning. Emission images were reconstructed by filtered back-projection and scatter corrected using the triple-energy window correction method. Both non-uniform Chang attenuation correction (one iteration) and uniform Sorenson correction (attenuation coefficient 0.09 cm -1 ) were applied. Images were automatically re-oriented to a stereotactic template on which 35 predefined VOIs were defined for semi-quantification (normalisation on total VOI counts). Small but significant differences between relative VOI uptake values for NUAC versus UAC in the infratentorial region were found. VOI standard deviations were significantly smaller for UAC, 4.5% (range 2.6-7.5), than for NUAC, 5.0% (2.3-9.0) (P 99m Tc-ECD uptake values in healthy volunteers to those obtained with NUAC, although values for the infratentorial region are slightly lower. NUAC produces a slight increase in inter-subject variability. Further study is necessary in various patient populations to establish the full clinical impact of NUAC in brain perfusion SPET. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Paula Madeira Fortes

    2017-06-01

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

  4. MRI of the brain stem using fluid attenuated inversion recivery pulse sequences

    International Nuclear Information System (INIS)

    De Coene, B.; Hajnal, J.V.; Pennock, J.M.; Bydder, G.M.

    1993-01-01

    Heavily T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences with inversion times of 2000-2500 ms and echo times of 130-200 ms were used to image the brain stem of a normal adult and five patients. These sequences produce high signal from many white matter tracts and display high lesion contrast. The corticospinal and parietopontine tracts, lateral and medial lemnisci, superior and inferior cerebellar peduncles, medial longitudinal fasciculi, thalamo-olivary tracts the cuneate and gracile fasiculi gave high signal and were directly visualised. The oculomotor and trigeminal nerves were demonstrated within the brain stem. Lesions not seen with conventional T2-weighted spin echo sequences were seen with high contrast in patients with infarction, multiple sclerosis, sarcoidosis, chunt obstruction and metastatic tumour. The anatomical detail and high lesion contrast given by the FLAIR pulse sequence appear likely to be of value in diagnosis of disease in the brain stem. (orig.)

  5. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    Science.gov (United States)

    Weaver, John; Yang, Yirong; Purvis, Rebecca; Weatherwax, Theodore; Rosen, Gerald M.; Liu, Ke Jian

    2014-01-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O2 may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O2 is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO2 in vivo remains largely uncharacterized. This study investigated striatal tissue pO2 changes in male C57BL/6 mice (16–20g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO2 in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO2 was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO2 to 64%. More importantly, pO2 did not recover fully to control levels even 24 hrs after administration of a single dose of METH. and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO2 indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO2, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. PMID:24412707

  6. Improvement of brain perfusion SPET using iterative reconstruction with scatter and non-uniform attenuation correction

    Energy Technology Data Exchange (ETDEWEB)

    Kauppinen, T.; Vanninen, E.; Kuikka, J.T. [Kuopio Central Hospital (Finland). Dept. of Clinical Physiology; Koskinen, M.O. [Dept. of Clinical Physiology and Nuclear Medicine, Tampere Univ. Hospital, Tampere (Finland); Alenius, S. [Signal Processing Lab., Tampere Univ. of Technology, Tampere (Finland)

    2000-09-01

    Filtered back-projection (FBP) is generally used as the reconstruction method for single-photon emission tomography although it produces noisy images with apparent streak artefacts. It is possible to improve the image quality by using an algorithm with iterative correction steps. The iterative reconstruction technique also has an additional benefit in that computation of attenuation correction can be included in the process. A commonly used iterative method, maximum-likelihood expectation maximisation (ML-EM), can be accelerated using ordered subsets (OS-EM). We have applied to the OS-EM algorithm a Bayesian one-step late correction method utilising median root prior (MRP). Methodological comparison was performed by means of measurements obtained with a brain perfusion phantom and using patient data. The aim of this work was to quantitate the accuracy of iterative reconstruction with scatter and non-uniform attenuation corrections and post-filtering in SPET brain perfusion imaging. SPET imaging was performed using a triple-head gamma camera with fan-beam collimators. Transmission and emission scans were acquired simultaneously. The brain phantom used was a high-resolution three-dimensional anthropomorphic JB003 phantom. Patient studies were performed in ten chronic pain syndrome patients. The images were reconstructed using conventional FBP and iterative OS-EM and MRP techniques including scatter and nonuniform attenuation corrections. Iterative reconstructions were individually post-filtered. The quantitative results obtained with the brain perfusion phantom were compared with the known actual contrast ratios. The calculated difference from the true values was largest with the FBP method; iteratively reconstructed images proved closer to the reality. Similar findings were obtained in the patient studies. The plain OS-EM method improved the contrast whereas in the case of the MRP technique the improvement in contrast was not so evident with post-filtering. (orig.)

  7. Improvement of brain perfusion SPET using iterative reconstruction with scatter and non-uniform attenuation correction

    International Nuclear Information System (INIS)

    Kauppinen, T.; Vanninen, E.; Kuikka, J.T.; Alenius, S.

    2000-01-01

    Filtered back-projection (FBP) is generally used as the reconstruction method for single-photon emission tomography although it produces noisy images with apparent streak artefacts. It is possible to improve the image quality by using an algorithm with iterative correction steps. The iterative reconstruction technique also has an additional benefit in that computation of attenuation correction can be included in the process. A commonly used iterative method, maximum-likelihood expectation maximisation (ML-EM), can be accelerated using ordered subsets (OS-EM). We have applied to the OS-EM algorithm a Bayesian one-step late correction method utilising median root prior (MRP). Methodological comparison was performed by means of measurements obtained with a brain perfusion phantom and using patient data. The aim of this work was to quantitate the accuracy of iterative reconstruction with scatter and non-uniform attenuation corrections and post-filtering in SPET brain perfusion imaging. SPET imaging was performed using a triple-head gamma camera with fan-beam collimators. Transmission and emission scans were acquired simultaneously. The brain phantom used was a high-resolution three-dimensional anthropomorphic JB003 phantom. Patient studies were performed in ten chronic pain syndrome patients. The images were reconstructed using conventional FBP and iterative OS-EM and MRP techniques including scatter and nonuniform attenuation corrections. Iterative reconstructions were individually post-filtered. The quantitative results obtained with the brain perfusion phantom were compared with the known actual contrast ratios. The calculated difference from the true values was largest with the FBP method; iteratively reconstructed images proved closer to the reality. Similar findings were obtained in the patient studies. The plain OS-EM method improved the contrast whereas in the case of the MRP technique the improvement in contrast was not so evident with post-filtering. (orig.)

  8. Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice.

    Science.gov (United States)

    Yuan, Jichao; Liu, Wei; Zhu, Haitao; Zhang, Xuan; Feng, Yang; Chen, Yaxing; Feng, Hua; Lin, Jiangkai

    2017-01-01

    Early brain injury, one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. We induced SAH in mice via endovascular perforation, administered curcumin 15 min after surgery and evaluated neurologic scores, brain water content, Evans blue extravasation, Western blot assay results, and immunohistochemical analysis results 24 h after surgery. Curcumin significantly improved neurologic scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. At last, curcumin treatment increased the expression of the tight junction proteins zonula occludens-1 and occludin in treated mice compared with vehicle-treated and sample SAH mice. We demonstrated that curcumin inhibits microglial activation and matrix metallopeptidase-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-05-02

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

  10. Evaluation of MLACF based calculated attenuation brain PET imaging for FDG patient studies

    Science.gov (United States)

    Bal, Harshali; Panin, Vladimir Y.; Platsch, Guenther; Defrise, Michel; Hayden, Charles; Hutton, Chloe; Serrano, Benjamin; Paulmier, Benoit; Casey, Michael E.

    2017-04-01

    Calculating attenuation correction for brain PET imaging rather than using CT presents opportunities for low radiation dose applications such as pediatric imaging and serial scans to monitor disease progression. Our goal is to evaluate the iterative time-of-flight based maximum-likelihood activity and attenuation correction factors estimation (MLACF) method for clinical FDG brain PET imaging. FDG PET/CT brain studies were performed in 57 patients using the Biograph mCT (Siemens) four-ring scanner. The time-of-flight PET sinograms were acquired using the standard clinical protocol consisting of a CT scan followed by 10 min of single-bed PET acquisition. Images were reconstructed using CT-based attenuation correction (CTAC) and used as a gold standard for comparison. Two methods were compared with respect to CTAC: a calculated brain attenuation correction (CBAC) and MLACF based PET reconstruction. Plane-by-plane scaling was performed for MLACF images in order to fix the variable axial scaling observed. The noise structure of the MLACF images was different compared to those obtained using CTAC and the reconstruction required a higher number of iterations to obtain comparable image quality. To analyze the pooled data, each dataset was registered to a standard template and standard regions of interest were extracted. An SUVr analysis of the brain regions of interest showed that CBAC and MLACF were each well correlated with CTAC SUVrs. A plane-by-plane error analysis indicated that there were local differences for both CBAC and MLACF images with respect to CTAC. Mean relative error in the standard regions of interest was less than 5% for both methods and the mean absolute relative errors for both methods were similar (3.4%  ±  3.1% for CBAC and 3.5%  ±  3.1% for MLACF). However, the MLACF method recovered activity adjoining the frontal sinus regions more accurately than CBAC method. The use of plane-by-plane scaling of MLACF images was found to be a

  11. Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury.

    Science.gov (United States)

    Kim, Jae Young; Lee, Yong Woo; Kim, Jae Hwan; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

    2015-07-01

    Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-κB (NF-κB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-κB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.

  12. Magnetic resonance imaging-guided attenuation and scatter corrections in three-dimensional brain positron emission tomography

    CERN Document Server

    Zaidi, H; Slosman, D O

    2003-01-01

    Reliable attenuation correction represents an essential component of the long chain of modules required for the reconstruction of artifact-free, quantitative brain positron emission tomography (PET) images. In this work we demonstrate the proof of principle of segmented magnetic resonance imaging (MRI)-guided attenuation and scatter corrections in 3D brain PET. We have developed a method for attenuation correction based on registered T1-weighted MRI, eliminating the need of an additional transmission (TX) scan. The MR images were realigned to preliminary reconstructions of PET data using an automatic algorithm and then segmented by means of a fuzzy clustering technique which identifies tissues of significantly different density and composition. The voxels belonging to different regions were classified into air, skull, brain tissue and nasal sinuses. These voxels were then assigned theoretical tissue-dependent attenuation coefficients as reported in the ICRU 44 report followed by Gaussian smoothing and additio...

  13. Administration of Tauroursodeoxycholic Acid Attenuates Early Brain Injury via Akt Pathway Activation

    Directory of Open Access Journals (Sweden)

    Dongdong Sun

    2017-07-01

    Full Text Available Traumatic brain injury (TBI is one of the leading causes of trauma-induced mortality and disability, and emerging studies have shown that endoplasmic reticulum (ER stress plays an important role in the pathophysiology of TBI. Tauroursodeoxycholic acid (TUDCA, a hydrophilic bile acid, has been reported to act as an ER stress inhibitor and chemical chaperone and to have the potential to attenuate apoptosis and inflammation. To study the effects of TUDCA on brain injury, we subjected mice to TBI with a controlled cortical impact (CCI device. Using western blotting, we first examined TBI-induced changes in the expression levels of GRP78, an ER stress marker, p-PERK, PERK, p-eIF2a, eIF2a, ATF4, p-Akt, Akt, Pten, Bax, Bcl-2, Caspase-12 and CHOP, as well as changes in the mRNA levels of Akt, GRP78, Caspase-12 and CHOP using RT-PCR. Neuronal cell death was assessed by a terminal deoxynucleotidyl transferase (TdT-mediated dUTP nick end-labeling (TUNEL assay, and CHOP expression in neuronal cells was detected by double-immunofluorescence staining. Neurological and motor deficits were assessed by modified neurological severity scores (mNSS and beam balance and beam walking tests, and brain water content was also assessed. Our results indicated that ER stress peaked at 72 h after TBI and that TUDCA abolished ER stress and inhibited p-PERK, p-eIF2a, ATF4, Pten, Caspase-12 and CHOP expression levels. Moreover, our results show that TUDCA also improved neurological function and alleviated brain oedema. Additionally, TUDCA increased p-Akt expression and the Bcl-2/Bax ratio. However, the administration of the Akt inhibitor MK2206 or siRNA targeting of Akt abolished the beneficial effects of TUDCA. Taken together, our results indicate that TUDCA may attenuate early brain injury via Akt pathway activation.

  14. 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.

    Directory of Open Access Journals (Sweden)

    Kristen N. Segovia

    2013-05-01

    Full Text Available Considerable evidence indicates that the metabolite of ethanol (EtOH, acetaldehyde, is biologically active. Acetaldehyde can be formed from EtOH peripherally mainly by alcohol dehydrogenase, 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.

  15. Neuro-chemical activation of brain reward meso-limbic circuitry is associated with relapse prevention and drug hunger: a hypothesis.

    Science.gov (United States)

    Blum, Kenneth; Gold, Mark S

    2011-04-01

    drug use in adolescents. Exploration of various treatment approaches for the most part reveal poor outcomes in terms of relapse prevention and continued drug hunger. The authors are proposing a new paradigm shift in residential, non-residential and aftercare involving the incorporation of genetic testing to identify risk alleles coupled with D2 receptor stimulation using neuroadatogen amino acid precursor enkephlinase--catecholamine-methyltransferase (COMT) inhibition therapy. A natural but therapeutic nutraceutical formulation potentially induces DA release could cause the induction of D2-directed mRNA and proliferation of D2 receptors in the human. We further hypothesize that this proliferation of D2 receptors in turn will induce the attenuation of drug-like craving behavior. Finally, pharmacological therapies have had limited success because these powerful agents have focused on maintenance or interference with drug euphoria rather than correcting or compensating for pre-morbid dopamine system deficits These concepts await further confirmation via required neuro-imaging studies. Copyright © 2011. Published by Elsevier Ltd.

  16. MR-based attenuation correction in brain PET based on UTE sequences

    Energy Technology Data Exchange (ETDEWEB)

    Cabello, Jorge; Nekolla, Stephan G; Ziegler, Sibylle I [Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München (Germany)

    2014-07-29

    Attenuation correction (AC) in brain PET/MR has recently emerged as one of the challenging tasks in the PET/MR field. It has been shown that to ignore the attenuation produced by bone can lead to errors ranging from 5-30% in regions close to bone structures. Since the information provided by the MR signal is not directly related to tissue attenuation, alternative methods have to be developed. Signal from bone tissue is difficult to measure given its short transverse relaxation time (T2). Ultrashort-echo time (UTE) pulse sequences were developed to measure signal from tissues with short T2. A combination of two consecutive UTE echoes has been used in several works to measure signal from bone tissue. The first echo is able to measure signal from bone tissue in addition to soft tissue, while the second echo contains most of the soft tissue contained in the first echo but not bone. In this work we extract the attenuation information from the difference between the logarithm of two images obtained after applying two consecutive UTE pulse sequences using the mMR scanner (Siemens Healthcare). Subsequently, image processing techniques are applied to reduce the noise and extract air cavities within the head. The resulting image is converted to linear attenuation coefficients, generating what is known as µ-map, to be used during reconstruction. For comparison purposes PET/CT scans of the same patients were acquired prior to the PET/MR scan. Additional µ-maps obtained for comparison were extracted from a Dixon sequence (used in clinical routine) and an additional µ-map calculated by the scanner based on UTE pulse sequences. Preliminary quantitative results measured in the cerebellum, using the value obtained with CT-based AC as reference, show differences of 34% without AC, 13% using the Dixon-based and UTE-based provided by the scanner, and 0.8% with the AC strategy presented here.

  17. Compulsive Sexual Behavior: Prefrontal and Limbic Volume and Interactions

    DEFF Research Database (Denmark)

    Schmidt, Casper; Morris, Laurel S.; Kvamme, Timo L.

    2017-01-01

    with matched healthy volunteers (HV). Methods: Structural MRI (MPRAGE) data were collected in 92 subjects (23 CSB males and 69 age-matched male HV) and analyzed using voxel-based morphometry. Resting state functional MRI data using multi-echo planar sequence and independent components analysis (ME-ICA) were...... prefrontal cortex (whole brain, cluster corrected FWE P motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions...

  18. An Aminopyridazine Inhibitor of Death Associated Protein Kinase Attenuates Hypoxia-Ischemia Induced Brain Damage

    Energy Technology Data Exchange (ETDEWEB)

    Velentza, A.V.; Wainwright, M.S.; Zasadzki, M.; Mirzoeva, S.; Haiech, J.; Focia, P.J.; Egli, M.; Watterson, D.M.

    2010-03-08

    Death associated protein kinase (DAPK) is a calcium and calmodulin regulated enzyme that functions early in eukaryotic programmed cell death, or apoptosis. To validate DAPK as a potential drug discovery target for acute brain injury, the first small molecule DAPK inhibitor was synthesized and tested in vivo. A single injection of the aminopyridazine-based inhibitor administered 6 h after injury attenuated brain tissue or neuronal biomarker loss measured, respectively, 1 week and 3 days later. Because aminopyridazine is a privileged structure in neuropharmacology, we determined the high-resolution crystal structure of a binary complex between the kinase domain and a molecular fragment of the DAPK inhibitor. The co-crystal structure describes a structural basis for interaction and provides a firm foundation for structure-assisted design of lead compounds with appropriate molecular properties for future drug development.

  19. Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    Sergey A Sosunov

    Full Text Available This study demonstrates that in mice subjected to hypoxia-ischemia (HI brain injury isoflurane anesthesia initiated upon reperfusion limits a release of mitochondrial oxidative radicals by inhibiting a recovery of complex-I dependent mitochondrial respiration. This significantly attenuates an oxidative stress and reduces the extent of HI brain injury. Neonatal mice were subjected to HI, and at the initiation of reperfusion were exposed to isoflurane with or without mechanical ventilation. At the end of HI and isoflurane exposure cerebral mitochondrial respiration, H2O2 emission rates were measured followed by an assessment of cerebral oxidative damage and infarct volumes. At 8 weeks after HI navigational memory and brain atrophy were assessed. In vitro, direct effect of isoflurane on mitochondrial H2O2 emission was compared to that of complex-I inhibitor, rotenone. Compared to controls, 15 minutes of isoflurane anesthesia inhibited recovery of the compex I-dependent mitochondrial respiration and decreased H2O2 production in mitochondria supported with succinate. This was associated with reduced oxidative brain injury, superior navigational memory and decreased cerebral atrophy compared to the vehicle-treated HI-mice. Extended isoflurane anesthesia was associated with sluggish recovery of cerebral blood flow (CBF and the neuroprotection was lost. However, when isoflurane anesthesia was supported with mechanical ventilation the CBF recovery improved, the event associated with further reduction of infarct volume compared to HI-mice exposed to isoflurane without respiratory support. Thus, in neonatal mice brief isoflurane anesthesia initiated at the onset of reperfusion limits mitochondrial release of oxidative radicals and attenuates an oxidative stress. This novel mechanism contributes to neuroprotective action of isoflurane. The use of mechanical ventilation during isoflurane anesthesia counterbalances negative effect of isoflurane anesthesia on

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

    Science.gov (United States)

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

    2014-10-01

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

  1. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    International Nuclear Information System (INIS)

    Weaver, John; Yang, Yirong; Purvis, Rebecca; Weatherwax, Theodore; Rosen, Gerald M.; Liu, Ke Jian

    2014-01-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O 2 may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O 2 is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO 2 in vivo remains largely uncharacterized. This study investigated striatal tissue pO 2 changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO 2 in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO 2 was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO 2 to 64%. More importantly, pO 2 did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO 2 indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO 2 , which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO 2 in vivo after METH administration by EPR oximetry. • pO 2 was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO 2 did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO 2 may be associated with a decrease in CBF. • Administration of methamphetamine may lead to hypoxic

  2. In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, John, E-mail: jmweaver@salud.unm.edu [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Yang, Yirong [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Purvis, Rebecca [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Weatherwax, Theodore [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Rosen, Gerald M. [Center for Biomedical Engineering and Technology, University of Maryland, Baltimore, MD 21201 (United States); Center for EPR Imaging In Vivo Physiology, University of Maryland, Baltimore, MD 21201 (United States); Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201 (United States); Liu, Ke Jian [Center of Biomedical Research Excellence, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    2014-03-01

    Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O{sub 2} may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O{sub 2} is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO{sub 2}in vivo remains largely uncharacterized. This study investigated striatal tissue pO{sub 2} changes in male C57BL/6 mice (16–20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO{sub 2}in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO{sub 2} was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO{sub 2} to 64%. More importantly, pO{sub 2} did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO{sub 2} indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO{sub 2}, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults. - Highlights: • Explored striatal tissue pO{sub 2}in vivo after METH administration by EPR oximetry. • pO{sub 2} was reduced by 81% after a single dose and 64% after 3 consecutive daily doses. • pO{sub 2} did not recover fully to control levels even 24 h after a single dose. • Decrease in brain tissue pO{sub 2} may be associated with a decrease in

  3. Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs.

    Science.gov (United States)

    Zhang, Hai-Tao; Zhang, Ping; Gao, Yi; Li, Chen-Long; Wang, Hong-Jun; Chen, Ling-Chao; Feng, Yan; Li, Rui-Yan; Li, Yong-Li; Jiang, Chuan-Lu

    2017-01-01

    Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90‑min period, either an anti‑VEGF neutralizing antibody (RB‑222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion. Functional outcomes, BBB leakage, brain edema, microvessel numbers and the relative protein levels of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, occludin and collagen-IV were then determined using neurological assessments, Evans Blue staining, brain water content, CD31 staining and western blotting. Treatment with RB‑222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion; 10 µg RB‑222 was more effective than a 5 µg dose of the antibody. In addition, RB‑222 reduced the number of immature microvessels, which subsequently attenuated BBB permeability. RB‑222 significantly repressed VEGF expression as well as decreased MMP‑2 and MMP‑9 expression. However, it enhanced occludin and collagen‑IV levels in the ischemic rat brain compared with the MCAO and IgG groups. Taken together, the results indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.

  4. Influence of attenuation correction and reconstruction techniques on the detection of hypoperfused lesions in brain SPECT studies

    International Nuclear Information System (INIS)

    Ghoorun, S.; Groenewald, W.A.; Baete, K.; Nuyts, J.; Dupont, P.

    2004-01-01

    Full text: Aim: To study the influence of attenuation correction and the reconstruction technique on the detection of hypoperfused lesions in brain SPECT imaging, Material and Methods: A simulation experiment was used in which the effects of attenuation and reconstruction were decoupled, A high resolution SPECT phantom was constructed using the BrainWeb database, In this phantom, activity values were assigned to grey and white matter (ratio 4:1) and scaled to obtain counts of the same magnitude as in clinical practice, The true attenuation map was generated by assigning attenuation coefficients to each tissue class (grey and white matter, cerebral spinal fluid, skull, soft and fatty tissue and air) to create a non-uniform attenuation map, The uniform attenuation map was calculated using an attenuation coefficient of 0.15 cm-1, Hypoperfused lesions of varying intensities and sizes were added. The phantom was then projected as typical SPECT projection data, taking into account attenuation and collimator blurring with the addition of Poisson noise, The projection data was reconstructed using four different methods of reconstruction: (1) filtered backprojection (FBP) with the uniform attenuation map; (2) FBP using the true attenuation map; (3) ordered subset expectation maximization (OSEM) (equivalent to 423 iterations) with a uniform attenuation map; and (4) OSEM with a true attenuation map. Different Gaussian postsmooth kernels were applied to the reconstructed images. Results: The analysis of the reconstructed data was performed using figures of merit such as signal to noise ratio (SNR), bias and variance. The results illustrated that uniform attenuation correction offered slight deterioration (less than 2%) with regard to SNR when compared to the ideal attenuation map. which in reality is not known. The iterative techniques produced superior signal to noise ratios (increase of 5 - 20 % depending on the lesion and the postsmooth) in comparison to the FBP methods

  5. Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.

    Science.gov (United States)

    Quinn, Emma J; Blumenfeld, Zack; Velisar, Anca; Koop, Mandy Miller; Shreve, Lauren A; Trager, Megan H; Hill, Bruce C; Kilbane, Camilla; Henderson, Jaimie M; Brontë-Stewart, Helen

    2015-11-01

    Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P closed-loop DBS. © 2015 International Parkinson and Movement Disorder Society.

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

    Science.gov (United States)

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

    2012-01-01

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

  7. High frequency deep brain stimulation attenuates subthalamic and cortical rhythms in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Diane eWhitmer

    2012-06-01

    Full Text Available Parkinson’s disease (PD is marked by excessive synchronous activity in the beta (8-35 Hz band throughout the cortico-basal ganglia network. The optimal location of high frequency deep brain stimulation (HF DBS within the subthalamic nucleus (STN region and the location of maximal beta hypersynchrony are currently matters of debate. Additionally, the effect of STN HF DBS on neural synchrony in functionally connected regions of motor cortex is unknown and of great interest. Scalp EEG studies demonstrated that stimulation of the STN can activate motor cortex antidromically, but the spatial specificity of this effect has not been examined. The present study examined the effect of STN HF DBS on neural synchrony within the cortico-basal ganglia network in patients with PD. We measured local field potentials dorsal to and within the STN of PD patients, and additionally in the motor cortex in a subset of these patients. We used diffusion tensor imaging (DTI to guide the placement of subdural cortical surface electrodes over the DTI-identified origin of the hyperdirect pathway between motor cortex and the STN. The results demonstrated that local beta power was attenuated during HF DBS both dorsal to and within the STN. The degree of attenuation was monotonic with increased DBS voltages in both locations, but this voltage-dependent effect was greater in the central STN than dorsal to the STN (p < 0.05. Cortical signals over the estimated origin of the hyperdirect pathway also demonstrated attenuation of beta hypersynchrony during DBS dorsal to or within STN, whereas signals from non-specific regions of motor cortex were not attenuated. The spatially specific suppression of beta synchrony in the motor cortex support the hypothesis that DBS may treat Parkinsonism by reducing excessive synchrony in the functionally connected sensorimotor network.

  8. Kisspeptin modulates sexual and emotional brain processing in humans.

    Science.gov (United States)

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

    2017-02-01

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

  9. White matter segmentation by estimating tissue optical attenuation from volumetric OCT massive histology of whole rodent brains

    Science.gov (United States)

    Lefebvre, Joël.; Castonguay, Alexandre; Lesage, Frédéric

    2017-02-01

    A whole rodent brain was imaged using an automated massive histology setup and an Optical Coherence Tomography (OCT) microscope. Thousands of OCT volumetric tiles were acquired, each covering a size of about 2.5x2.5x0.8 mm3 with a sampling resolution of 4.9x4.9x6.5 microns. This paper shows the techniques for reconstruction, attenuation compensation and segmentation of the sliced brains. The tile positions within the mosaic were evaluated using a displacement model of the motorized stage and pairwise coregistration. Volume blending was then performed by solving the 3D Laplace equation, and consecutive slices were assembled using the cross-correlation of their 2D image gradient. This reconstruction algorithm resulted in a 3D map of optical reflectivity for the whole brain at micrometric resolution. OCT tissue slices were then used to estimate the local attenuation coefficient based on a single scattering photon model. The attenuation map obtained exhibits a high contrast for all white matter fibres, regardless of their orientation. The tissue optical attenuation from the intrinsic OCT reflectivity contributes to better white matter tissue segmentation. The combined 3D maps of reflectivity and attenuation is a step toward the study of white matter at a microscopic scale for the whole brain in small animals.

  10. Thymoquinone Attenuates Brain Injury via an Anti-oxidative Pathway in a Status Epilepticus Rat Model.

    Science.gov (United States)

    Shao, Yi-Ye; Li, Bing; Huang, Yong-Mei; Luo, Qiong; Xie, Yang-Mei; Chen, Ying-Hui

    2017-01-01

    Status epilepticus (SE) results in the generation of reactive oxygen species (ROS), which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black cumin (Nigella sativa) seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway. Electroencephalogram and Racine scale were used to value seizure severity. Passive-avoidance test was used to determine learning and memory function. Moreover, anti-oxidative activity of TQ was observed using Western blot and super oxide dismutase (SOD) activity assay. Latency to SE increased in the TQ-pretreated group compared with rats in the model group, while the total power was significantly lower. Seizure severity measured on the Racine scale was significantly lower in the TQ group compared with the model group. Results of behavioral experiments suggest that TQ may also have a protective effect on learning and memory function. Investigation of the protective mechanism of TQ showed that TQ-pretreatment significantly increased the expression of Nrf2, HO-1 proteins and SOD in the hippocampus. These findings showed that TQ attenuated brain injury induced by SE via an anti-oxidative pathway.

  11. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    Science.gov (United States)

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

    2015-01-01

    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  12. Comparison between MRI-based attenuation correction methods for brain PET in dementia patients

    International Nuclear Information System (INIS)

    Cabello, Jorge; Lukas, Mathias; Pyka, Thomas; Nekolla, Stephan G.; Ziegler, Sibylle I.; Rota Kops, Elena; Shah, N. Jon; Ribeiro, Andre; Yakushev, Igor

    2016-01-01

    The combination of Positron Emission Tomography (PET) with magnetic resonance imaging (MRI) in hybrid PET/MRI scanners offers a number of advantages in investigating brain structure and function. A critical step of PET data reconstruction is attenuation correction (AC). Accounting for bone in attenuation maps (μ-map) was shown to be important in brain PET studies. While there are a number of MRI-based AC methods, no systematic comparison between them has been performed so far. The aim of this work was to study the different performance obtained by some of the recent methods presented in the literature. To perform such a comparison, we focused on [ 18 F]-Fluorodeoxyglucose-PET/MRI neurodegenerative dementing disorders, which are known to exhibit reduced levels of glucose metabolism in certain brain regions. Four novel methods were used to calculate μ-maps from MRI data of 15 patients with Alzheimer's dementia (AD). The methods cover two atlas-based methods, a segmentation method, and a hybrid template/segmentation method. Additionally, the Dixon-based and a UTE-based method, offered by a vendor, were included in the comparison. Performance was assessed at three levels: tissue identification accuracy in the μ-map, quantitative accuracy of reconstructed PET data in specific brain regions, and precision in diagnostic images at identifying hypometabolic areas. Quantitative regional errors of -20-10 % were obtained using the vendor's AC methods, whereas the novel methods produced errors in a margin of ±5 %. The obtained precision at identifying areas with abnormally low levels of glucose uptake, potentially regions affected by AD, were 62.9 and 79.5 % for the two vendor AC methods, the former ignoring bone and the latter including bone information. The precision increased to 87.5-93.3 % in average for the four new methods, exhibiting similar performances. We confirm that the AC methods based on the Dixon and UTE sequences provided by the vendor are inferior

  13. Comparison between MRI-based attenuation correction methods for brain PET in dementia patients

    Energy Technology Data Exchange (ETDEWEB)

    Cabello, Jorge; Lukas, Mathias; Pyka, Thomas; Nekolla, Stephan G.; Ziegler, Sibylle I. [Technische Universitaet Muenchen, Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Munich (Germany); Rota Kops, Elena; Shah, N. Jon [Forschungszentrum Juelich GmbH, Institute of Neuroscience and Medicine 4, Medical Imaging Physics, Juelich (Germany); Ribeiro, Andre [Forschungszentrum Juelich GmbH, Institute of Neuroscience and Medicine 4, Medical Imaging Physics, Juelich (Germany); Institute of Biophysics and Biomedical Engineering, Lisbon (Portugal); Yakushev, Igor [Technische Universitaet Muenchen, Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Munich (Germany); Institute TUM Neuroimaging Center (TUM-NIC), Munich (Germany)

    2016-11-15

    The combination of Positron Emission Tomography (PET) with magnetic resonance imaging (MRI) in hybrid PET/MRI scanners offers a number of advantages in investigating brain structure and function. A critical step of PET data reconstruction is attenuation correction (AC). Accounting for bone in attenuation maps (μ-map) was shown to be important in brain PET studies. While there are a number of MRI-based AC methods, no systematic comparison between them has been performed so far. The aim of this work was to study the different performance obtained by some of the recent methods presented in the literature. To perform such a comparison, we focused on [{sup 18}F]-Fluorodeoxyglucose-PET/MRI neurodegenerative dementing disorders, which are known to exhibit reduced levels of glucose metabolism in certain brain regions. Four novel methods were used to calculate μ-maps from MRI data of 15 patients with Alzheimer's dementia (AD). The methods cover two atlas-based methods, a segmentation method, and a hybrid template/segmentation method. Additionally, the Dixon-based and a UTE-based method, offered by a vendor, were included in the comparison. Performance was assessed at three levels: tissue identification accuracy in the μ-map, quantitative accuracy of reconstructed PET data in specific brain regions, and precision in diagnostic images at identifying hypometabolic areas. Quantitative regional errors of -20-10 % were obtained using the vendor's AC methods, whereas the novel methods produced errors in a margin of ±5 %. The obtained precision at identifying areas with abnormally low levels of glucose uptake, potentially regions affected by AD, were 62.9 and 79.5 % for the two vendor AC methods, the former ignoring bone and the latter including bone information. The precision increased to 87.5-93.3 % in average for the four new methods, exhibiting similar performances. We confirm that the AC methods based on the Dixon and UTE sequences provided by the vendor are

  14. Education attenuates the negative impact of traumatic brain injury on cognitive status.

    Science.gov (United States)

    Sumowski, James F; Chiaravalloti, Nancy; Krch, Denise; Paxton, Jessica; Deluca, John

    2013-12-01

    To investigate whether the cognitive reserve hypothesis helps to explain differential cognitive impairment among survivors of traumatic brain injury (TBI), whereby survivors with greater intellectual enrichment (estimated with education) are less vulnerable to cognitive impairment. Cross-sectional study. Medical rehabilitation research center. Survivors of moderate or severe TBI (n=44) and healthy controls (n=36). Not applicable. Intellectual enrichment was estimated with educational attainment. Group was defined as TBI or healthy control. Current cognitive status (processing speed, working memory, episodic memory) was evaluated with neuropsychological tasks. TBI survivors exhibited worse cognitive status than healthy persons (Peducation was positively correlated with cognitive status in TBI survivors (r=.54, Peducation (R(2) change=.036, P=.004), whereas higher education attenuated the negative impact of TBI on cognitive status. TBI survivors with lower education performed much worse than matched healthy persons, but this TBI-related performance discrepancy was attenuated at higher levels of education. Higher intellectual enrichment (estimated with education) reduces the negative effect of TBI on cognitive outcomes, thereby supporting the cognitive reserve hypothesis in persons with TBI. Future work is necessary to investigate whether intellectual enrichment can build cognitive reserve as a rehabilitative intervention in survivors of TBI. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  15. The relative contributions of scatter and attenuation corrections toward improved brain SPECT quantification

    International Nuclear Information System (INIS)

    Stodilka, Robert Z.; Msaki, Peter; Prato, Frank S.; Nicholson, Richard L.; Kemp, B.J.

    1998-01-01

    Mounting evidence indicates that scatter and attenuation are major confounds to objective diagnosis of brain disease by quantitative SPECT. There is considerable debate, however, as to the relative importance of scatter correction (SC) and attenuation correction (AC), and how they should be implemented. The efficacy of SC and AC for 99m Tc brain SPECT was evaluated using a two-compartment fully tissue-equivalent anthropomorphic head phantom. Four correction schemes were implemented: uniform broad-beam AC, non-uniform broad-beam AC, uniform SC+AC, and non-uniform SC+AC. SC was based on non-stationary deconvolution scatter subtraction, modified to incorporate a priori knowledge of either the head contour (uniform SC) or transmission map (non-uniform SC). The quantitative accuracy of the correction schemes was evaluated in terms of contrast recovery, relative quantification (cortical:cerebellar activity), uniformity ((coefficient of variation of 230 macro-voxels) x100%), and bias (relative to a calibration scan). Our results were: uniform broad-beam (μ=0.12cm -1 ) AC (the most popular correction): 71% contrast recovery, 112% relative quantification, 7.0% uniformity, +23% bias. Non-uniform broad-beam (soft tissue μ=0.12cm -1 ) AC: 73%, 114%, 6.0%, +21%, respectively. Uniform SC+AC: 90%, 99%, 4.9%, +12%, respectively. Non-uniform SC+AC: 93%, 101%, 4.0%, +10%, respectively. SC and AC achieved the best quantification; however, non-uniform corrections produce only small improvements over their uniform counterparts. SC+AC was found to be superior to AC; this advantage is distinct and consistent across all four quantification indices. (author)

  16. Ivy Sign on Fluid-Attenuated Inversion Recovery Images in Moyamoya Disease: Correlation with Clinical Severity and Old Brain Lesions

    OpenAIRE

    Seo, Kwon-Duk; Suh, Sang Hyun; Kim, Yong Bae; Kim, Ji Hwa; Ahn, Sung Jun; Kim, Dong-Seok; Lee, Kyung-Yul

    2015-01-01

    Purpose Leptomeningeal collateral, in moyamoya disease (MMD), appears as an ivy sign on fluid-attenuated inversion-recovery (FLAIR) images. There has been little investigation into the relationship between presentation of ivy signs and old brain lesions. We aimed to evaluate clinical significance of ivy signs and whether they correlate with old brain lesions and the severity of clinical symptoms in patients with MMD. Materials and Methods FLAIR images of 83 patients were reviewed. Each cerebr...

  17. PET/MR brain imaging: evaluation of clinical UTE-based attenuation correction

    International Nuclear Information System (INIS)

    Aasheim, Lars Birger; Karlberg, Anna; Goa, Paal Erik; Haaberg, Asta; Soerhaug, Sveinung; Fagerli, Unn-Merete; Eikenes, Live

    2015-01-01

    One of the greatest challenges in PET/MR imaging is that of accurate MR-based attenuation correction (AC) of the acquired PET data, which must be solved if the PET/MR modality is to reach its full potential. The aim of this study was to investigate the performance of Siemens' most recent version (VB20P) of MR-based AC of head PET data, by comparing it to CT-based AC. Methods: 18 F-FDG PET data from seven lymphoma and twelve lung cancer patients examined with a Biograph mMR PET/MR system were reconstructed with both CT-based and MR-based AC, avoiding sources of error arising when comparing PET data from different systems. The resulting images were compared quantitatively by measuring changes in mean SUV in ten different brain regions in both hemispheres, as well as the brainstem. In addition, the attenuation maps (μ maps) were compared regarding volume and localization of cranial bone. The UTE μ maps clearly overestimate the amount of bone in the neck, while slightly underestimating the amount of bone in the cranium, and the localization of bone in the cranial region also differ from the CT μ maps. In air/tissue interfaces in the sinuses and ears, the MRAC method struggles to correctly classify the different tissues. The misclassification of tissue is most likely caused by a combination of artefacts and the insufficiency of the UTE method to accurately separate bone. Quantitatively, this results in a combination of overestimation (0.5-3.6 %) and underestimation (2.7-5.2 %) of PET activity throughout the brain, depending on the proximity to the inaccurate regions. Our results indicate that the performance of the UTE method as implemented in VB20P is close to the theoretical maximum of such an MRAC method in the brain, while it does not perform satisfactorily in the neck or face/nasal area. Further improvement of the UTE MRAC or other available methods for more accurate segmentation of bone should be incorporated. (orig.)

  18. Imaging of limbic para-neoplastic encephalitis

    International Nuclear Information System (INIS)

    Rimmelin, A.; Sellat, F.; Morand, G.; Quoix, E.; Clouet, P.L.; Dietemann, J.L.

    1997-01-01

    Para-neoplastic limbic encephalitis is a rare syndrome mostly associated with small cell lung cancer. We present the case of a 69-year-old man with selective amnesia suggesting limbic encephalitis. A neuroendocrine cell lung cancer was found, confirming the diagnostics of para-neoplastic limbic encephalitis. Contrast-enhanced cerebral CT was normal whether magnetic resonance imaging showed signal abnormalities of the medial part of temporal lobes and hippocampal regions. Because neurologic improvement may follow treatment of the primary tumor, early diagnosis is important. (authors)

  19. Contrast-enhanced fast fluid-attenuated inversion recovery MR imaging in patients with brain tumors

    International Nuclear Information System (INIS)

    Kim, Chan Kyo; Na, Dong Gyu; Ryoo, Wook Jae; Byun Hong Sik; Yoon, Hye Kyung; Kim, Jong hyun

    2000-01-01

    To assess the feasibility of contrast-enhanced fast fluid-attenuated inversion recovery (fast FLAIR) MR imaging in patients with brain tumors. This study involved 31 patients with pathologically proven brain tumors and nine with clinically diagnosed metastases. In all patients, T2-weighted, fast FLAIR, images were visual contrast-enhanced T1-weighted MR images were obtained. Contrast-enhanced fast FLAIR images were visually compared with other MR sequences in terms of tumor conspicuity. In order to distinguish tumor and surrounding edema, contrast-enhanced fast FLAIR images were compared with fast FLAIR and T2-weighted images. The tumor-to- white matter contrast-to-noise ratios (CNRs), as demonstrated by T2-weighted, fast FLAIR, contrast-enhanced fast FLAIR and contrast-enhanced T1-weighted imaging, were quantitatively assessed and compared. For the visual assessment of tumor conspicuity, contrast-enhanced fast FLAIR image imaging superior to fast FLAIR in 60% of cases (24/40), and superior to T2-weighted in 70% (28/40). Contrast-enhanced fast FLAIR imaging was inferior to contrast-enhanced T1-weighted in 58% of cases (23/40). For distinguishing between tumor and surrounding edema, contrast-enhanced fast FLAIR imaging was superior to fast FLAIR or T2-weighted in 22 of 27 tumors with peritumoral edema (81%). Quantitatively, CNR was the highest on contrast-enhanced fast FLAIR image and the lowest on fast FLAIR. For the detection of leptomeningeal metastases, contrast-enhanced fast FLAIR was partially superior to contrast-enhanced T1-weighted imaging in two of three high-grade gliomas. Although contrast-enhanced fast FLAIR imaging should not be seen as a replacement for conventional modalities, it provides additional informaton for assessment of the extent of glial cell tumors and leptomeningeal metastases in patients with brain tumors. (author)

  20. Curcumin attenuates collagen-induced inflammatory response through the "gut-brain axis".

    Science.gov (United States)

    Dou, Yannong; Luo, Jinque; Wu, Xin; Wei, Zhifeng; Tong, Bei; Yu, Juntao; Wang, Ting; Zhang, Xinyu; Yang, Yan; Yuan, Xusheng; Zhao, Peng; Xia, Yufeng; Hu, Huijuan; Dai, Yue

    2018-01-06

    Previous studies have demonstrated that oral administration of curcumin exhibited an anti-arthritic effect despite its poor bioavailability. The present study aimed to explore whether the gut-brain axis is involved in the therapeutic effect of curcumin. The collagen-induced arthritis (CIA) rat model was induced by immunization with an emulsion of collagen II and complete Freund's adjuvant. Sympathetic and parasympathetic tones were measured by electrocardiographic recordings. Unilateral cervical vagotomy (VGX) was performed before the induction of CIA. The ChAT, AChE activities, and serum cytokine levels were determined by ELISA. The expression of the high-affinity choline transporter 1 (CHT1), ChAT, and vesicular acetylcholine transporter (VAChT) were determined by real-time PCR and immunohistochemical staining. The neuronal excitability of the vagus nerve was determined by whole-cell patch clamp recording. Oral administration of curcumin restored the imbalance between the sympathetic and parasympathetic tones in CIA rats and increased ChAT activity and expression of ChAT and VAChT in the gut, brain, and synovium. Additionally, VGX eliminated the effects of curcumin on arthritis and ACh biosynthesis and transport. Electrophysiological data showed that curcumin markedly increased neuronal excitability of the vagus nerve. Furthermore, selective α7 nAChR antagonists abolished the effects of curcumin on CIA. Our results demonstrate that curcumin attenuates CIA through the "gut-brain axis" by modulating the function of the cholinergic system. These findings provide a novel approach for mechanistic studies of anti-arthritic compounds with low oral absorption and bioavailability.

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

    Directory of Open Access Journals (Sweden)

    Zhuo Wang

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

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

    Science.gov (United States)

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

    2013-01-01

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

  3. Inhibition of type I insulin-like growth factor receptor signaling attenuates the development of breast cancer brain metastasis.

    Science.gov (United States)

    Saldana, Sandra M; Lee, Heng-Huan; Lowery, Frank J; Khotskaya, Yekaterina B; Xia, Weiya; Zhang, Chenyu; Chang, Shih-Shin; Chou, Chao-Kai; Steeg, Patricia S; Yu, Dihua; Hung, Mien-Chie

    2013-01-01

    Brain metastasis is a common cause of mortality in cancer patients, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF-IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that IGF-IR is constitutively autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased migration and invasion of MDA-MB-231Br brain-seeking cells. In addition, transient ablation of IGFBP3, which is overexpressed in brain-seeking cells, blocks IGF-IR activation. Using an in vivo experimental brain metastasis model, we show that IGF-IR knockdown brain-seeking cells have reduced potential to establish brain metastases. Finally, we demonstrate that the malignancy of brain-seeking cells is attenuated by pharmacological inhibition with picropodophyllin, an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the IGF-IR is an important mediator of brain metastasis and its ablation delays the onset of brain metastases in our model system.

  4. Effects of scatter and attenuation corrections on phantom and clinical brain SPECT

    International Nuclear Information System (INIS)

    Prando, S.; Robilotta, C.C.R.; Oliveira, M.A.; Alves, T.C.; Busatto Filho, G.

    2002-01-01

    Aim: The present work evaluated the effects of combinations of scatter and attenuation corrections on the analysis of brain SPECT. Materials and Methods: We studied images of the 3D Hoffman brain phantom and from a group of 20 depressive patients with confirmed cardiac insufficiency (CI) and 14 matched healthy controls (HC). Data were acquired with a Sophy-DST/SMV-GE dual-head camera after venous injection of 1110MBq 99m Tc-HMPAO. Two energy windows, 15% on 140keV and 30% centered on 108keV of the Compton distribution, were used to obtain corresponding sets of 128x128x128 projections. Tomograms were reconstructed using OSEM (2 iterations, 8 sub-sets) and Metz filter (order 8, 4 pixels FWHM psf) and FBP with Butterworth filter (order 10, frequency 0.7 Nyquist). Ten combinations of Jaszczak correction (factors 0.3, 0.4 and 0.5) and the 1st order Chang correction (u=0.12cm -1 and 0.159cm -1 ) were applied on the phantom data. In all the phantom images, contrast and signal-noise ratio between 3 ROIs (ventricle, occipital and thalamus) and cerebellum, as well as the ratio between activities in gray and white matters, were calculated and compared with the expected values. The patients images were corrected with k=0.5 and u=0.159cm -1 and reconstructed with OSEM and Metz filter. The images were inspected visually and blood flow comparisons between the CI and the HC groups were performed using Statistical Parametric Mapping (SPM). Results: The best results in the analysis of the contrast and activities ratio were obtained with k=0.5 and u=0.159cm -1 . The results of the activities ratio obtained with OSEM e Metz filter are similar to those published by Laere et al.[J.Nucl.Med 2000;41:2051-2062]. The method of correction using effective attenuation coefficient produced results visually acceptable, but inadequate for the quantitative evaluation. The results of signal-noise ratio are better with OSEM than FBP reconstruction method. The corrections in the CI patients studies

  5. Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress.

    Science.gov (United States)

    Li, Qin; Bi, Ming Jun; Bi, Wei Kang; Kang, Hai; Yan, Le Jing; Guo, Yun-Liang

    2016-03-01

    Acute carbon monoxide (CO) poisoning is the most common cause of death from poisoning all over the world and may result in neuropathologic and neurophysiologic changes. Acute brain damage and delayed encephalopathy are the most serious complication, yet their pathogenesis is poorly understood. The present study aimed to evaluate the neuroprotective effects of Edaravone against apoptosis and oxidative stress after acute CO poisoning. The rat model of CO poisoning was established in a hyperbaric oxygen chamber by exposed to CO. Ultrastructure changes were observed by transmission electron microscopy (TEM). TUNEL stain was used to assess apoptosis. Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf-2) protein and their relationship. By dynamically monitored the carboxyhemoglobin (HbCO) level in blood, we successfully established rat model of severe CO poisoning. Ultrastructure changes, including chromatin condensation, cytoplasm dissolution, vacuoles formation, nucleus membrane and cell organelles decomposition, could be observed after CO poisoning. Edaravone could improve the ultrastructure damage. CO poisoning could induce apoptosis. Apoptotic cells were widely distributed in cortex, striatum and hippocampus. Edaravone treatment attenuated neuronal apoptosis as compared with the poisoning group (P Edaravone, the expression of HO-1 and Nrf-2 significantly increased (P Edaravone may inhibit apoptosis, activate the Keapl-Nrf/ARE pathway, and thus improve the ultrastructure damage and neurophysiologic changes following acute CO poisoning. © 2014 Wiley Periodicals, Inc.

  6. Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway.

    Science.gov (United States)

    Li, Chunyi; Mo, Zhihuai; Lei, Junjie; Li, Huiqing; Fu, Ruying; Huang, Yanxia; Luo, Shijian; Zhang, Lei

    2018-06-01

    Edaravone is a new type of oxygen free radical scavenger and able to attenuate various brain damage including hypoxic-ischemic brain damage (HIBD). This study was aimed at investigating the neuroprotective mechanism of edaravone in rat hypoxic-ischemic brain damage model and its correlation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway. 75 seven-day-old Sprague-Dawley neonatal rats were equally divided into three groups: sham-operated group (sham), HIBD group and HIBD rats injected with edaravone (HIBD + EDA) group. Neurological severity and space cognitive ability of rats in each group were evaluated using Longa neurological severity score and Morris water maze testing. TUNEL assay and flow cytometry were used to determine brain cell apoptosis. Western blot was used to estimate the expression level of death receptor-5 (DR5), Fas-associated protein with death domain (FADD), caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). In addition, immunofluorescence was performed to detect caspase 3. Edaravone reduced neurofunctional damage caused by HIBD and improved the cognitive capability of rats. The above experiment results suggested that edaravone could down-regulate the expression of active caspase 3 protein, thereby relieving neuronal apoptosis. Taken together, edaravone could attenuate neuronal apoptosis in rat hypoxic-ischemic brain damage model via suppression of TRAIL signaling pathway, which also suggested that edaravone might be an effective therapeutic strategy for HIBD clinical treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Work-related social support modulates effects of early life stress on limbic reactivity during stress.

    Science.gov (United States)

    Leicht-Deobald, Ulrich; Bruch, Heike; Bönke, Luisa; Stevense, Amie; Fan, Yan; Bajbouj, Malek; Grimm, Simone

    2017-12-15

    Early life stress (ELS) affects stress- reactivity via limbic brain regions implicated such as hippocampus and amygdala. Social support is a major protective factor against ELS effects, while subjects with ELS experience reportedly perceive less of it in their daily life. The workplace, where most adults spend a substantial amount of time in their daily lives, might serve as a major resource for social support. Since previous data demonstrated that social support attenuates stress reactivity, we here used a psychosocial stress task to test the hypothesis that work-related social support modulates the effects of ELS. Results show decreased amygdala reactivity during stress in ELS subjects who report high levels of work- related social support, thereby indicating a signature for reduced stress reactivity. However, this effect was only observable on the neural, but not on the behavioral level, since social support had no buffering effect regarding the subjective experience of stress in daily life as well as regarding feelings of uncontrollability induced by the stress task. Accordingly, our data suggest that subjects with ELS experiences might benefit from interventions targeted at lowering their subjective stress levels by helping them to better perceive the availability of social support in their daily lives.

  8. Limbic control of aggression in the cat.

    Science.gov (United States)

    Adamec, R E; Stark-Adamec, C I

    1983-01-01

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

  9. Maturation of the limbic system revealed by MR FLAIR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Jacques F.; Vergesslich, Klara [University Children' s Hospital UKBB, Department of Paediatric Radiology, Basel (Switzerland)

    2007-04-15

    Cortical signal intensity (SI) of the limbic system in adults is known to be higher than in neocortical structures, but time-related changes in SI during childhood have not been described. To detect maturation-related SI changes within the limbic system using a fluid-attenuated inversion recovery (FLAIR) MR sequence. Twenty children (10 boys, 10 girls; age 3.5-18 years, mean 11.2 years) with no neurological abnormality and normal MR imaging examination were retrospectively selected. On two coronal FLAIR slices, ten regions of interest (ROI) with a constant area of 10 mm{sup 2} were manually placed in the archeocortex (hippocampus), periarcheocortex (parahippocampal gyrus, subcallosal area, cingulate gyrus) and in the neocortex at the level of the superior frontal gyrus on both sides. Significant SI gradients were observed with a higher intensity in the archeocortex, intermediate intensity in the periarcheocortex and low intensity in the neocortex. Significant higher SI values in hippocampal and parahippocampal structures were detected in children up to 10 years of age. These differences mainly reflected differences in cortical structure and myelination state. Archeocortical structures especially showed significant age-related intensity progression suggesting ongoing organization and/or myelination until early adolescence. (orig.)

  10. Maturation of the limbic system revealed by MR FLAIR imaging

    International Nuclear Information System (INIS)

    Schneider, Jacques F.; Vergesslich, Klara

    2007-01-01

    Cortical signal intensity (SI) of the limbic system in adults is known to be higher than in neocortical structures, but time-related changes in SI during childhood have not been described. To detect maturation-related SI changes within the limbic system using a fluid-attenuated inversion recovery (FLAIR) MR sequence. Twenty children (10 boys, 10 girls; age 3.5-18 years, mean 11.2 years) with no neurological abnormality and normal MR imaging examination were retrospectively selected. On two coronal FLAIR slices, ten regions of interest (ROI) with a constant area of 10 mm 2 were manually placed in the archeocortex (hippocampus), periarcheocortex (parahippocampal gyrus, subcallosal area, cingulate gyrus) and in the neocortex at the level of the superior frontal gyrus on both sides. Significant SI gradients were observed with a higher intensity in the archeocortex, intermediate intensity in the periarcheocortex and low intensity in the neocortex. Significant higher SI values in hippocampal and parahippocampal structures were detected in children up to 10 years of age. These differences mainly reflected differences in cortical structure and myelination state. Archeocortical structures especially showed significant age-related intensity progression suggesting ongoing organization and/or myelination until early adolescence. (orig.)

  11. Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR

    Science.gov (United States)

    Mérida, Inés; Reilhac, Anthonin; Redouté, Jérôme; Heckemann, Rolf A.; Costes, Nicolas; Hammers, Alexander

    2017-04-01

    In simultaneous PET-MR, attenuation maps are not directly available. Essential for absolute radioactivity quantification, they need to be derived from MR or PET data to correct for gamma photon attenuation by the imaged object. We evaluate a multi-atlas attenuation correction method for brain imaging (MaxProb) on static [18F]FDG PET and, for the first time, on dynamic PET, using the serotoninergic tracer [18F]MPPF. A database of 40 MR/CT image pairs (atlases) was used. The MaxProb method synthesises subject-specific pseudo-CTs by registering each atlas to the target subject space. Atlas CT intensities are then fused via label propagation and majority voting. Here, we compared these pseudo-CTs with the real CTs in a leave-one-out design, contrasting the MaxProb approach with a simplified single-atlas method (SingleAtlas). We evaluated the impact of pseudo-CT accuracy on reconstructed PET images, compared to PET data reconstructed with real CT, at the regional and voxel levels for the following: radioactivity images; time-activity curves; and kinetic parameters (non-displaceable binding potential, BPND). On static [18F]FDG, the mean bias for MaxProb ranged between 0 and 1% for 73 out of 84 regions assessed, and exceptionally peaked at 2.5% for only one region. Statistical parametric map analysis of MaxProb-corrected PET data showed significant differences in less than 0.02% of the brain volume, whereas SingleAtlas-corrected data showed significant differences in 20% of the brain volume. On dynamic [18F]MPPF, most regional errors on BPND ranged from -1 to  +3% (maximum bias 5%) for the MaxProb method. With SingleAtlas, errors were larger and had higher variability in most regions. PET quantification bias increased over the duration of the dynamic scan for SingleAtlas, but not for MaxProb. We show that this effect is due to the interaction of the spatial tracer-distribution heterogeneity variation over time with the degree of accuracy of the attenuation maps. This

  12. Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hao; Rose, Marie E. [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurology, University of Pittsburgh School of Medicine, PA (United States); Culver, Sherman; Ma, Xiecheng; Dixon, C. Edward [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurosurgery, University of Pittsburgh, PA 15216 (United States); Department of Critical Care Medicine, University of Pittsburgh, PA 15216 (United States); Graham, Steven H., E-mail: Steven.Graham@va.gov [Geriatric Research Educational and Clinical Center, V.A. Pittsburgh Healthcare System, PA (United States); Department of Neurology, University of Pittsburgh School of Medicine, PA (United States)

    2016-04-15

    Rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been shown to confer neuroprotective effects in stroke and spinal cord injury, but its role in the traumatic brain injury (TBI) is still controversial. Using a controlled cortical impact model in rats, the current study was designed to determine the effects of rosiglitazone treatment (6 mg/kg at 5 min, 6 h and 24 h post injury) upon inflammation and histological outcome at 21 d after TBI. In addition, the effects of rosiglitazone upon inflammatory cytokine transcription, vestibulomotor behavior and spatial memory function were determined at earlier time points (24 h, 1–5 d, 14–20 d post injury, respectively). Compared with the vehicle-treated group, rosiglitazone treatment suppressed production of TNFα at 24 h after TBI, attenuated activation of microglia/macrophages and increased survival of CA3 neurons but had no effect on lesion volume at 21 d after TBI. Rosiglitazone-treated animals had improved performance on beam balance testing, but there was no difference in spatial memory function as determined by Morris water maze. In summary, this study indicates that rosiglitazone treatment in the first 24 h after TBI has limited anti-inflammatory and neuroprotective effects in rat traumatic injury. Further study using an alternative dosage paradigm and more sensitive behavioral testing may be warranted. - Highlights: • Effects of rosiglitazone after CCI were evaluated using a rat TBI model. • Rosiglitazone suppressed production of TNFα at 24 h after CCI. • Rosiglitazone inhibited microglial activation at 21 d after CCI. • Rosiglitazone increased survival of CA3 neurons at 21 d after CCI. • Rosiglitazone-treated animals had improved performance in beam balance testing.

  13. Rosiglitazone attenuates inflammation and CA3 neuronal loss following traumatic brain injury in rats

    International Nuclear Information System (INIS)

    Liu, Hao; Rose, Marie E.; Culver, Sherman; Ma, Xiecheng; Dixon, C. Edward; Graham, Steven H.

    2016-01-01

    Rosiglitazone, a potent peroxisome proliferator-activated receptor (PPAR)-γ agonist, has been shown to confer neuroprotective effects in stroke and spinal cord injury, but its role in the traumatic brain injury (TBI) is still controversial. Using a controlled cortical impact model in rats, the current study was designed to determine the effects of rosiglitazone treatment (6 mg/kg at 5 min, 6 h and 24 h post injury) upon inflammation and histological outcome at 21 d after TBI. In addition, the effects of rosiglitazone upon inflammatory cytokine transcription, vestibulomotor behavior and spatial memory function were determined at earlier time points (24 h, 1–5 d, 14–20 d post injury, respectively). Compared with the vehicle-treated group, rosiglitazone treatment suppressed production of TNFα at 24 h after TBI, attenuated activation of microglia/macrophages and increased survival of CA3 neurons but had no effect on lesion volume at 21 d after TBI. Rosiglitazone-treated animals had improved performance on beam balance testing, but there was no difference in spatial memory function as determined by Morris water maze. In summary, this study indicates that rosiglitazone treatment in the first 24 h after TBI has limited anti-inflammatory and neuroprotective effects in rat traumatic injury. Further study using an alternative dosage paradigm and more sensitive behavioral testing may be warranted. - Highlights: • Effects of rosiglitazone after CCI were evaluated using a rat TBI model. • Rosiglitazone suppressed production of TNFα at 24 h after CCI. • Rosiglitazone inhibited microglial activation at 21 d after CCI. • Rosiglitazone increased survival of CA3 neurons at 21 d after CCI. • Rosiglitazone-treated animals had improved performance in beam balance testing.

  14. Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-α and lipopolysaccharide in mice.

    Science.gov (United States)

    Zielinski, Mark R; Dunbrasky, Danielle L; Taishi, Ping; Souza, Gianne; Krueger, James M

    2013-08-01

    Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration. Vagotomy blocks enhanced sleep induced by systemic TNF-α and LPS in rats, suggesting that vagal afferent stimulation by TNF-α enhances pro-inflammatory cytokines in sleep-related brain areas. However, the effects of systemic TNF-α on brain cytokine expression and mouse sleep remain unknown. We investigated the role of vagal afferents on brain cytokines and sleep after systemically applied TNF-α or LPS in mice. Spontaneous sleep was similar in vagotomized and sham-operated controls. Vagotomy attenuated TNF-α- and LPS-enhanced non-rapid eye movement sleep (NREMS); these effects were more evident after lower doses of these substances. Vagotomy did not affect rapid eye movement sleep responses to these substances. NREMS electroencephalogram delta power (0.5-4 Hz range) was suppressed after peripheral TNF-α or LPS injections, although vagotomy did not affect these responses. Compared to sham-operated controls, vagotomy did not affect liver cytokines. However, vagotomy attenuated interleukin-1 beta (IL-1β) and TNF-α mRNA brain levels after TNF-α, but not after LPS, compared to the sham-operated controls. We conclude that vagal afferents mediate peripheral TNF-α-induced brain TNF-α and IL-1β mRNA expressions to affect sleep. We also conclude that vagal afferents alter sleep induced by peripheral pro-inflammatory stimuli in mice similar to those occurring in other species.

  15. Subject-specific bone attenuation correction for brain PET/MR: can ZTE-MRI substitute CT scan accurately?

    Science.gov (United States)

    Khalifé, Maya; Fernandez, Brice; Jaubert, Olivier; Soussan, Michael; Brulon, Vincent; Buvat, Irène; Comtat, Claude

    2017-10-01

    In brain PET/MR applications, accurate attenuation maps are required for accurate PET image quantification. An implemented attenuation correction (AC) method for brain imaging is the single-atlas approach that estimates an AC map from an averaged CT template. As an alternative, we propose to use a zero echo time (ZTE) pulse sequence to segment bone, air and soft tissue. A linear relationship between histogram normalized ZTE intensity and measured CT density in Hounsfield units (HU ) in bone has been established thanks to a CT-MR database of 16 patients. Continuous AC maps were computed based on the segmented ZTE by setting a fixed linear attenuation coefficient (LAC) to air and soft tissue and by using the linear relationship to generate continuous μ values for the bone. Additionally, for the purpose of comparison, four other AC maps were generated: a ZTE derived AC map with a fixed LAC for the bone, an AC map based on the single-atlas approach as provided by the PET/MR manufacturer, a soft-tissue only AC map and, finally, the CT derived attenuation map used as the gold standard (CTAC). All these AC maps were used with different levels of smoothing for PET image reconstruction with and without time-of-flight (TOF). The subject-specific AC map generated by combining ZTE-based segmentation and linear scaling of the normalized ZTE signal into HU was found to be a good substitute for the measured CTAC map in brain PET/MR when used with a Gaussian smoothing kernel of 4~mm corresponding to the PET scanner intrinsic resolution. As expected TOF reduces AC error regardless of the AC method. The continuous ZTE-AC performed better than the other alternative MR derived AC methods, reducing the quantification error between the MRAC corrected PET image and the reference CTAC corrected PET image.

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

    Directory of Open Access Journals (Sweden)

    Jiliang Fang

    2012-01-01

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

  17. CT-based attenuation correction and resolution compensation for I-123 IMP brain SPECT normal database: a multicenter phantom study.

    Science.gov (United States)

    Inui, Yoshitaka; Ichihara, Takashi; Uno, Masaki; Ishiguro, Masanobu; Ito, Kengo; Kato, Katsuhiko; Sakuma, Hajime; Okazawa, Hidehiko; Toyama, Hiroshi

    2018-03-19

    Statistical image analysis of brain SPECT images has improved diagnostic accuracy for brain disorders. However, the results of statistical analysis vary depending on the institution even when they use a common normal database (NDB), due to different intrinsic spatial resolutions or correction methods. The present study aimed to evaluate the correction of spatial resolution differences between equipment and examine the differences in skull bone attenuation to construct a common NDB for use in multicenter settings. The proposed acquisition and processing protocols were those routinely used at each participating center with additional triple energy window (TEW) scatter correction (SC) and computed tomography (CT) based attenuation correction (CTAC). A multicenter phantom study was conducted on six imaging systems in five centers, with either single photon emission computed tomography (SPECT) or SPECT/CT, and two brain phantoms. The gray/white matter I-123 activity ratio in the brain phantoms was 4, and they were enclosed in either an artificial adult male skull, 1300 Hounsfield units (HU), a female skull, 850 HU, or an acrylic cover. The cut-off frequency of the Butterworth filters was adjusted so that the spatial resolution was unified to a 17.9 mm full width at half maximum (FWHM), that of the lowest resolution system. The gray-to-white matter count ratios were measured from SPECT images and compared with the actual activity ratio. In addition, mean, standard deviation and coefficient of variation images were calculated after normalization and anatomical standardization to evaluate the variability of the NDB. The gray-to-white matter count ratio error without SC and attenuation correction (AC) was significantly larger for higher bone densities (p correction. The proposed protocol showed potential for constructing an appropriate common NDB from SPECT images with SC, AC and spatial resolution compensation.

  18. Attenuation correction for brain PET imaging using deep neural network based on dixon and ZTE MR images.

    Science.gov (United States)

    Gong, Kuang; Yang, Jaewon; Kim, Kyungsang; El Fakhri, Georges; Seo, Youngho; Li, Quanzheng

    2018-05-23

    Positron Emission Tomography (PET) is a functional imaging modality widely used in neuroscience studies. To obtain meaningful quantitative results from PET images, attenuation correction is necessary during image reconstruction. For PET/MR hybrid systems, PET attenuation is challenging as Magnetic Resonance (MR) images do not reflect attenuation coefficients directly. To address this issue, we present deep neural network methods to derive the continuous attenuation coefficients for brain PET imaging from MR images. With only Dixon MR images as the network input, the existing U-net structure was adopted and analysis using forty patient data sets shows it is superior than other Dixon based methods. When both Dixon and zero echo time (ZTE) images are available, we have proposed a modified U-net structure, named GroupU-net, to efficiently make use of both Dixon and ZTE information through group convolution modules when the network goes deeper. Quantitative analysis based on fourteen real patient data sets demonstrates that both network approaches can perform better than the standard methods, and the proposed network structure can further reduce the PET quantification error compared to the U-net structure. © 2018 Institute of Physics and Engineering in Medicine.

  19. [The limbic system and the motivation process].

    Science.gov (United States)

    Karli, P

    1968-01-01

    Understanding the part played by the limbic system in the shaping of overall behaviour is assisted by the previous study of that system's involvement in the mechanisms underlying certain sections of behaviour. a) Limbic structures contribute to the dynamic synthesis of contemporary information, by reason of their share in mechanisms: I. of modulatory central control in the production and transmission of sensory messages, 2. in the genesis of states of vigilance, especially the focussing of attention. On the other hand, they have an inhibitory role in somatic motility by way of progressive elimination of all inadequate motor response. b) Limbic structures participate in the elaboration of emotional states, in the initiation of both positive and negative reinforcement. That is to say they participate in the processes by which: I. "appetitive" or "aversive" significance is progressively conferred upon a given stimulus or situation, 2. behaviour is subjected to a positive or negative reinforcement, assuring its stabilization or its extinction. c) The comparison of the present situation with experience, enabling the organism to foresee the results of its behaviour; and similarly the comparison of results achieved with those anticipated, imply information storage, and the formation of lasting memory traces. It appears that the limbic system by integration of cognitive and affective components of sensory information, contributes to the compilation of experience which can be drawn upon in recognition or evocation. When the lasting results of different limbic lesions upon total behaviour are studied, it is clear that these effects are all the more profound as, among the motivational factors involved, those due to experience and to adaptation to environment, play the more important part. Behavioural deficits appear especially due to the absence of inhibition of certain inadequate responses, which results in a "maladaptation" of behavior as much towards present environmental

  20. Diminished fronto-limbic functional connectivity in child sexual offenders.

    Science.gov (United States)

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

    2018-02-22

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

  1. The Subthalamic Nucleus, Limbic Function, and Impulse Control.

    Science.gov (United States)

    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.

  2. Impaired autonomic responses to emotional stimuli in autoimmune limbic encephalitis

    Directory of Open Access Journals (Sweden)

    Olga eSchröder

    2015-11-01

    Full Text Available 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.

  3. Clinical usefulness of scatter and attenuation correction for brain single photon emission computed tomography (SPECT) in pediatrics

    International Nuclear Information System (INIS)

    Adachi, Itaru; Doi, Kenji; Komori, Tsuyoshi; Hou, Nobuyoshi; Tabuchi, Koujirou; Matsui, Ritsuo; Sueyoshi, Kouzou; Utsunomiya, Keita; Narabayashi, Isamu

    1998-01-01

    This investigation was undertaken to study clinical usefulness of scatter and attenuation correction (SAC) of brain SPECT in infants to compare the standard reconstruction (STD). The brain SPECT was performed in 31 patients with 19 epilepsy, 5 cerebro-vascular disease, 2 brain tumor, 3 meningitis, 1 hydrocephalus and psychosis (mean age 5.0±4.9 years old). Many patients was necessary to be injected sedatives for restraining body motion after Technetium-99m hexamethylpropylene amine oxime ( 99m Tc-HMPAO) was injected at the convulsion or rest. Brain SPECT data were acquired with triple detector gamma camera (GCA-9300 Toshiba Japan). These data were reconstructed by filtered backprojection after the raw data were corrected by triple energy windows method of scatter correction and Chang filtered method of attenuation correction. The same data was reconstructed by filtered backprojection without these corrections. Both SAC and STD SPECT images were analyzed by the visual interpretation. The uptake ratio of cerebral basal nuclei was calculated by the counts of the thalamus or lenticular nuclei divided by the cortex. All images of SAC method were excellent than that of STD method. The thalamic uptake ratio in SAC method was higher than that of STD method (1.22±0.09>0.87±0.22 p 1.02±0.16 p<0.01). Transmission scan is the most suitable method of absorption correction. But the transmission scan is not adequate for examination of children, because this scan needs a lot of time and the infants are exposed by the line source radioisotope. It was concluded that these scatter and absorption corrections were most suitable method for brain SPECT in pediatrics. (author)

  4. Clinical usefulness of scatter and attenuation correction for brain single photon emission computed tomography (SPECT) in pediatrics

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, Itaru; Doi, Kenji; Komori, Tsuyoshi; Hou, Nobuyoshi; Tabuchi, Koujirou; Matsui, Ritsuo; Sueyoshi, Kouzou; Utsunomiya, Keita; Narabayashi, Isamu [Osaka Medical Coll., Takatsuki (Japan)

    1998-01-01

    This investigation was undertaken to study clinical usefulness of scatter and attenuation correction (SAC) of brain SPECT in infants to compare the standard reconstruction (STD). The brain SPECT was performed in 31 patients with 19 epilepsy, 5 cerebro-vascular disease, 2 brain tumor, 3 meningitis, 1 hydrocephalus and psychosis (mean age 5.0{+-}4.9 years old). Many patients was necessary to be injected sedatives for restraining body motion after Technetium-99m hexamethylpropylene amine oxime ({sup 99m}Tc-HMPAO) was injected at the convulsion or rest. Brain SPECT data were acquired with triple detector gamma camera (GCA-9300 Toshiba Japan). These data were reconstructed by filtered backprojection after the raw data were corrected by triple energy windows method of scatter correction and Chang filtered method of attenuation correction. The same data was reconstructed by filtered backprojection without these corrections. Both SAC and STD SPECT images were analyzed by the visual interpretation. The uptake ratio of cerebral basal nuclei was calculated by the counts of the thalamus or lenticular nuclei divided by the cortex. All images of SAC method were excellent than that of STD method. The thalamic uptake ratio in SAC method was higher than that of STD method (1.22{+-}0.09>0.87{+-}0.22 p<0.01). The lenticular nuclear uptake ratio in SAC method was higher than that of STD method (1.26{+-}0.15>1.02{+-}0.16 p<0.01). Transmission scan is the most suitable method of absorption correction. But the transmission scan is not adequate for examination of children, because this scan needs a lot of time and the infants are exposed by the line source radioisotope. It was concluded that these scatter and absorption corrections were most suitable method for brain SPECT in pediatrics. (author)

  5. Pharmacologic inhibition of phospholipase C in the brain attenuates early memory formation in the honeybee (Apis mellifera L.

    Directory of Open Access Journals (Sweden)

    Shota Suenami

    2018-01-01

    Full Text Available Although the molecular mechanisms involved in learning and memory in insects have been studied intensively, the intracellular signaling mechanisms involved in early memory formation are not fully understood. We previously demonstrated that phospholipase C epsilon (PLCe, whose product is involved in calcium signaling, is almost selectively expressed in the mushroom bodies, a brain structure important for learning and memory in the honeybee. Here, we pharmacologically examined the role of phospholipase C (PLC in learning and memory in the honeybee. First, we identified four genes for PLC subtypes in the honeybee genome database. Quantitative reverse transcription-polymerase chain reaction revealed that, among these four genes, three, including PLCe, were expressed higher in the brain than in sensory organs in worker honeybees, suggesting their main roles in the brain. Edelfosine and neomycin, pan-PLC inhibitors, significantly decreased PLC activities in homogenates of the brain tissues. These drugs injected into the head of foragers significantly attenuated memory acquisition in comparison with the control groups, whereas memory retention was not affected. These findings suggest that PLC in the brain is involved in early memory formation in the honeybee. To our knowledge, this is the first report of a role for PLC in learning and memory in an insect.

  6. Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study

    International Nuclear Information System (INIS)

    Le Jeune, Florence; Peron, Julie; Grandjean, Didier; Drapier, Sophie; Verin, Marc; Haegelen, Claire; Garin, Etienne; Millet, Bruno

    2010-01-01

    Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD. We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using 18 F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS. The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits. These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role. (orig.)

  7. Subthalamic nucleus stimulation affects limbic and associative circuits: a PET study

    Energy Technology Data Exchange (ETDEWEB)

    Le Jeune, Florence [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France); Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Centre Eugene Marquis, Service Medecine Nucleaire, Rennes (France); Peron, Julie [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Clinique Neurologique, Rennes (France); University of Geneva, Neuroscience of Emotion and Affective Dynamics, Department of Psychology and Swiss Center for Affective Sciences, Geneva (Switzerland); Grandjean, Didier [University of Geneva, Neuroscience of Emotion and Affective Dynamics, Department of Psychology and Swiss Center for Affective Sciences, Geneva (Switzerland); Drapier, Sophie; Verin, Marc [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Clinique Neurologique, Rennes (France); Haegelen, Claire [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); Hopital Pontchaillou, CHU de Rennes, Service de Neurochirurgie, Rennes (France); Garin, Etienne [Centre Eugene Marquis, Service de Medecine Nucleaire, Rennes (France); Millet, Bruno [Universite Rennes 1, Hopital Pontchaillou, CHU de Rennes, Unite de Recherche Universitaire ' ' Comportement et Noyaux Gris Centraux' ' , Rennes (France); S.H.U. Psychiatrie Adulte, CH Guillaume Regnier, Rennes (France)

    2010-08-15

    Although high-frequency deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in advanced Parkinson's disease (PD), clinical studies have reported cognitive, motivational and emotional changes. These results suggest that the STN forms part of a broadly distributed neural network encompassing the associative and limbic circuits. We sought to pinpoint the cortical and subcortical brain areas modulated by STN DBS, in order to assess the STN's functional role and explain neuropsychological modifications following STN DBS in PD. We studied resting state glucose metabolism in 20 PD patients before and after STN DBS and 13 age-matched healthy controls using {sup 18}F-FDG PET. We used statistical analysis (SPM2) first to compare pre-stimulation metabolism in PD patients with metabolism in healthy controls, then to study metabolic modifications in PD patients following STN DBS. The first analysis revealed no pre-stimulation metabolic abnormalities in associative or limbic circuitry. After STN DBS, metabolic modifications were found in several regions known for their involvement in the limbic and associative circuits. These metabolic results confirm the STN's central role in associative and limbic basal ganglia circuits. They will provide information for working hypotheses for future studies investigating neuropsychological changes and metabolic modifications related to STN DBS, with a view to improving our knowledge of this structure's functional role. (orig.)

  8. Wired for behavior: from development to function of innate limbic system circuitry

    Directory of Open Access Journals (Sweden)

    Katie eSokolowski

    2012-04-01

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

  9. Influences of reconstruction and attenuation correction in brain SPECT images obtained by the hybrid SPECT/CT device: evaluation with a 3-dimensional brain phantom

    International Nuclear Information System (INIS)

    Akamatsu, Mana; Yamashita, Yasuo; Akamatsu, Go; Tsutsui, Yuji; Ohya, Nobuyoshi; Nakamura, Yasuhiko; Sasaki, Masayuki

    2014-01-01

    The aim of this study was to evaluate the influences of reconstruction and attenuation correction on the differences in the radioactivity distributions in 123 I brain SPECT obtained by the hybrid SPECT/CT device. We used the 3-dimensional (3D) brain phantom, which imitates the precise structure of gray matter, white matter and bone regions. It was filled with 123 I solution (20.1 kBq/mL) in the gray matter region and with K 2 HPO 4 in the bone region. The SPECT/CT data were acquired by the hybrid SPECT/CT device. SPECT images were reconstructed by using filtered back projection with uniform attenuation correction (FBP-uAC), 3D ordered-subsets expectation-maximization with uniform AC (3D-OSEM-uAC) and 3D OSEM with CT-based non-uniform AC (3D-OSEM-CTAC). We evaluated the differences in the radioactivity distributions among these reconstruction methods using a 3D digital phantom, which was developed from CT images of the 3D brain phantom, as a reference. The normalized mean square error (NMSE) and regional radioactivity were calculated to evaluate the similarity of SPECT images to the 3D digital phantom. The NMSE values were 0.0811 in FBP-uAC, 0.0914 in 3D-OSEM-uAC and 0.0766 in 3D-OSEM-CTAC. The regional radioactivity of FBP-uAC was 11.5% lower in the middle cerebral artery territory, and that of 3D-OSEM-uAC was 5.8% higher in the anterior cerebral artery territory, compared with the digital phantom. On the other hand, that of 3D-OSEM-CTAC was 1.8% lower in all brain areas. By using the hybrid SPECT/CT device, the brain SPECT reconstructed by 3D-OSEM with CT attenuation correction can provide an accurate assessment of the distribution of brain radioactivity

  10. Prelude to passion: limbic activation by "unseen" drug and sexual cues.

    Directory of Open Access Journals (Sweden)

    Anna Rose Childress

    2008-01-01

    Full Text Available 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?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.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.

  11. Curcumin pretreatment attenuates brain lesion size and improves neurological function following traumatic brain injury in the rat.

    Science.gov (United States)

    Samini, Fariborz; Samarghandian, Saeed; Borji, Abasalt; Mohammadi, Gholamreza; bakaian, Mahdi

    2013-09-01

    Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow coloring principle in turmeric, is a polyphenolic and a major active constituent. Besides anti-inflammatory, thrombolytic and anti-carcinogenic activities, curcumin also possesses strong antioxidant property. The neuroprotective effects of curcumin were evaluated in a weight drop model of cortical contusion trauma in rat. Male Wistar rats (350-400 g, n=9) were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and subjected to head injury. Five days before injury, animals randomly received an i.p. bolus of either curcumin (50 and 100 mg/kg/day, n=9) or vehicle (n=9). Two weeks after the injury and drug treatment, animals were sacrificed and a series of brain sections, stained with hematoxylin and eosin (H&E) were evaluated for quantitative brain lesion volume. Two weeks after the injury, oxidative stress parameter (malondialdehyde) was also measured in the brain. Curcumin (100 mg/kg) significantly reduced the size of brain injury-induced lesions (Pcurcumin (100 mg/kg). Curcumin treatment significantly improved the neurological status evaluated during 2 weeks after brain injury. The study demonstrates the protective efficacy of curcumin in rat traumatic brain injury model. © 2013 Elsevier Inc. All rights reserved.

  12. A rare case of autoimmune limbic encephalitis: an uncharted territory!

    Science.gov (United States)

    Ibrahim, Hatim; Al Jasser, Abdulelah N; Khan, Sonia A; Tlili, Kalthoum G

    2017-10-01

    Autoimmune encephalitis is rare. Several auto- antibodies are described in autoimmune encephalitis. We describe a case of autoimmune limbic encephalitis associated with positive voltage gated potassium channel (VGKC) antibodies and positive leucine-rich glioma inactivated protein 1 antibodies (LGI1). A 33-year-old Saudi housewife, she presented with 2 months history of cognitive deterioration and recurrent left facio-brachial dystonic seizures followed by generalized tonic clonic seizures. At times the seizures are preceded by rising epigastric aura and shortness of breath. The neurological examination was normal apart from upgoing left plantar reflex. She had borderline IQ of 76 with impaired verbal fluency and impaired visual and verbal memory. Magnetic resonance imaging of the brain showed right mesial temporal non-enhancing lesion. Cerebrospinal fluid examination was positive for LGI1 and VGKC. Optimal seizure control was achieved with immunotherapy.

  13. Towards Implementing an MR-based PET Attenuation Correction Method for Neurological Studies on the MR-PET Brain Prototype

    Science.gov (United States)

    Catana, Ciprian; van der Kouwe, Andre; Benner, Thomas; Michel, Christian J.; Hamm, Michael; Fenchel, Matthias; Fischl, Bruce; Rosen, Bruce; Schmand, Matthias; Sorensen, A. Gregory

    2013-01-01

    A number of factors have to be considered for implementing an accurate attenuation correction (AC) in a combined MR-PET scanner. In this work, some of these challenges were investigated and an AC method based entirely on the MR data obtained with a single dedicated sequence was developed and used for neurological studies performed with the MR-PET human brain scanner prototype. Methods The focus was on the bone/air segmentation problem, the bone linear attenuation coefficient selection and the RF coil positioning. The impact of these factors on the PET data quantification was studied in simulations and experimental measurements performed on the combined MR-PET scanner. A novel dual-echo ultra-short echo time (DUTE) MR sequence was proposed for head imaging. Simultaneous MR-PET data were acquired and the PET images reconstructed using the proposed MR-DUTE-based AC method were compared with the PET images reconstructed using a CT-based AC. Results Our data suggest that incorrectly accounting for the bone tissue attenuation can lead to large underestimations (>20%) of the radiotracer concentration in the cortex. Assigning a linear attenuation coefficient of 0.143 or 0.151 cm−1 to bone tissue appears to give the best trade-off between bias and variability in the resulting images. Not identifying the internal air cavities introduces large overestimations (>20%) in adjacent structures. Based on these results, the segmented CT AC method was established as the “silver standard” for the segmented MR-based AC method. Particular to an integrated MR-PET scanner, ignoring the RF coil attenuation can cause large underestimations (i.e. up to 50%) in the reconstructed images. Furthermore, the coil location in the PET field of view has to be accurately known. Good quality bone/air segmentation can be performed using the DUTE data. The PET images obtained using the MR-DUTE- and CT-based AC methods compare favorably in most of the brain structures. Conclusion An MR-DUTE-based AC

  14. Evaluation of Sinus/Edge-Corrected Zero-Echo-Time-Based Attenuation Correction in Brain PET/MRI.

    Science.gov (United States)

    Yang, Jaewon; Wiesinger, Florian; Kaushik, Sandeep; Shanbhag, Dattesh; Hope, Thomas A; Larson, Peder E Z; Seo, Youngho

    2017-11-01

    In brain PET/MRI, the major challenge of zero-echo-time (ZTE)-based attenuation correction (ZTAC) is the misclassification of air/tissue/bone mixtures or their boundaries. Our study aimed to evaluate a sinus/edge-corrected (SEC) ZTAC (ZTAC SEC ), relative to an uncorrected (UC) ZTAC (ZTAC UC ) and a CT atlas-based attenuation correction (ATAC). Methods: Whole-body 18 F-FDG PET/MRI scans were obtained for 12 patients after PET/CT scans. Only data acquired at a bed station that included the head were used for this study. Using PET data from PET/MRI, we applied ZTAC UC , ZTAC SEC , ATAC, and reference CT-based attenuation correction (CTAC) to PET attenuation correction. For ZTAC UC , the bias-corrected and normalized ZTE was converted to pseudo-CT with air (-1,000 HU for ZTE 0.75), and bone (-2,000 × [ZTE - 1] + 42 HU for 0.2 ≤ ZTE ≤ 0.75). Afterward, in the pseudo-CT, sinus/edges were automatically estimated as a binary mask through morphologic processing and edge detection. In the binary mask, the overestimated values were rescaled below 42 HU for ZTAC SEC For ATAC, the atlas deformed to MR in-phase was segmented to air, inner air, soft tissue, and continuous bone. For the quantitative evaluation, PET mean uptake values were measured in twenty 1-mL volumes of interest distributed throughout brain tissues. The PET uptake was compared using a paired t test. An error histogram was used to show the distribution of voxel-based PET uptake differences. Results: Compared with CTAC, ZTAC SEC achieved the overall PET quantification accuracy (0.2% ± 2.4%, P = 0.23) similar to CTAC, in comparison with ZTAC UC (5.6% ± 3.5%, P PET quantification in brain PET/MRI, comparable to the accuracy achieved by CTAC, particularly in the cerebellum. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  15. [VGKC antibodies associated with limbic encephalitis].

    Science.gov (United States)

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

    2005-06-01

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

  16. Clinical Evaluation of Zero-Echo-Time Attenuation Correction for Brain 18F-FDG PET/MRI: Comparison with Atlas Attenuation Correction.

    Science.gov (United States)

    Sekine, Tetsuro; Ter Voert, Edwin E G W; Warnock, Geoffrey; Buck, Alfred; Huellner, Martin; Veit-Haibach, Patrick; Delso, Gaspar

    2016-12-01

    Accurate attenuation correction (AC) on PET/MR is still challenging. The purpose of this study was to evaluate the clinical feasibility of AC based on fast zero-echo-time (ZTE) MRI by comparing it with the default atlas-based AC on a clinical PET/MR scanner. We recruited 10 patients with malignant diseases not located on the brain. In all patients, a clinically indicated whole-body 18 F-FDG PET/CT scan was acquired. In addition, a head PET/MR scan was obtained voluntarily. For each patient, 2 AC maps were generated from the MR images. One was atlas-AC, derived from T1-weighted liver acquisition with volume acceleration flex images (clinical standard). The other was ZTE-AC, derived from proton-density-weighted ZTE images by applying tissue segmentation and assigning continuous attenuation values to the bone. The AC map generated by PET/CT was used as a silver standard. On the basis of each AC map, PET images were reconstructed from identical raw data on the PET/MR scanner. All PET images were normalized to the SPM5 PET template. After that, these images were qualified visually and quantified in 67 volumes of interest (VOIs; automated anatomic labeling, atlas). Relative differences and absolute relative differences between PET images based on each AC were calculated. 18 F-FDG uptake in all 670 VOIs and generalized merged VOIs were compared using a paired t test. Qualitative analysis shows that ZTE-AC was robust to patient variability. Nevertheless, misclassification of air and bone in mastoid and nasal areas led to the overestimation of PET in the temporal lobe and cerebellum (%diff of ZTE-AC, 2.46% ± 1.19% and 3.31% ± 1.70%, respectively). The |%diff| of all 670 VOIs on ZTE was improved by approximately 25% compared with atlas-AC (ZTE-AC vs. atlas-AC, 1.77% ± 1.41% vs. 2.44% ± 1.63%, P PET in regions near the skull base. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  17. Attenuating brain inflammation, ischemia, and oxidative damage by hyperbaric oxygen in diabetic rats after heat stroke

    Directory of Open Access Journals (Sweden)

    Kai-Li Lee

    2013-08-01

    Conclusion: Our results suggest that, in diabetic animals, HBO2 therapy may improve outcomes of HS in part by reducing heat-induced activated inflammation and ischemic and oxidative damage in the hypothalamus and other brain regions.

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

    Directory of Open Access Journals (Sweden)

    Amelia S Koe

    2009-10-01

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

  19. Paraneoplastic limbic encephalitis presenting as a neurological emergency: a case report

    Directory of Open Access Journals (Sweden)

    Mehta Brijesh P

    2010-03-01

    Full Text Available Abstract Introduction Paraneoplastic limbic encephalitis remains a challenging clinical diagnosis with poor outcome if it is not recognized and treated early in the course of the disease. Case Presentation A 65-year-old Caucasian woman presented with generalized tonic-clonic seizures and increasing confusion shortly after a lung biopsy that led to the diagnosis of small-cell lung cancer. She had a complicated hospital course, and had recurrent respiratory distress due to aspiration pneumonia, and fluctuating mental status and seizures that were refractory to anti-epileptic drug treatment. Routine laboratory testing, magnetic resonance imaging of the brain, electroencephalogram, lumbar puncture, serum and cerebrospinal fluid tests for paraneoplastic antibodies, and chest computed tomography were performed on our patient. The diagnosis was paraneoplastic limbic encephalitis in the setting of small-cell lung cancer with positive N-type voltage-gated calcium channel antibody titer. Anti-epileptic drugs for seizures, chemotherapy for small-cell lung cancer, and intravenous immunoglobulin and steroids for paraneoplastic limbic encephalitis led to a resolution of her seizures and improved her mental status. Conclusion Early recognition of paraneoplastic limbic encephalitis and prompt intervention with immune therapies at the onset of presentation will probably translate into more favorable neurological outcomes.

  20. Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats.

    Science.gov (United States)

    Dai, Shuhui; Hua, Ya; Keep, Richard F; Novakovic, Nemanja; Fei, Zhou; Xi, Guohua

    2018-06-05

    Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocycline reduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2 ⁎ -weighted and T2 ⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain iron content, ventricle volume, lesion volume and brain swelling. Immunohistochemistry was used to examine changes in iron handling proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal iron overload with upregulated iron handling proteins, neuroinflammation, brain atrophy, neuronal loss and neurological deficits. Minocycline significantly reduced ICH-induced perihematomal iron overload and iron handling proteins. It further reduced brain swelling, neuroinflammation, neuronal loss, delayed brain atrophy and neurological deficits. These effects may be linked to the role of minocycline as an iron chelator as well as an inhibitor of neuroinflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

    Science.gov (United States)

    Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

    2015-01-01

    Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

  2. Limbic encephalitis: Clinical spectrum and long-term outcome from a developing country perspective

    Directory of Open Access Journals (Sweden)

    Sujit Abajirao Jagtap

    2014-01-01

    Full Text Available Introduction: Limbic encephalitis (LE is characterized by rapidly progressive short-term memory loss, psychiatric symptoms and seizures. We describe the clinical spectrum, underlying etiology and long-term follow-up of patients with LE from India. Materials and Methods: This prospective study included patients during the period of January 2009 and December 2011 with the clinical features consistent with LE with one or more of the following: (1 Magnetic resonance imaging (MRI evidence of temporal lobe involvement; (2 cerebrospinal fluid inflammatory abnormalities, or (3 detection of antineuronal antibodies. Patients with metastasis, infection, metabolic and nutritional deficits, stroke, were excluded. Results: There were 16 patients (9 females, mean age of presentation was 36.6 years (range 15-69 years. The mean duration of symptoms before presentation was 11 months (range 5 days-2 years. The most common symptom at presentation was short-term memory impairment in 7 patients followed by seizures in 5 and behavioral changes in three. Nine patients had seizures, 11 had change in behavior, language involvement in eight, cerebellar features in 3 and autonomic dysfunction in two. Four patients had associated malignancy, 3 of four presented with neurological symptoms and on investigations found to be have malignancy. Antineuronal antibody testing was done in 6 of 12 non paraneoplastic and two paraneoplastic patients, one positive for N-methyl-D-aspartate and one for anti-Hu antibody. MRI brain showed typical fluid attenuated inversion recovery or T2 bilateral temporal lobe hyperintensities in 50% of patients. At a mean follow-up of 21 months (3-36 months, 10 patients improved, 4 patients remained same and two patients expired. Conclusion: Early recognition of LE is important based upon clinical, MRI data in the absence of antineuronal surface antibody screen in developing nations. Early institution of immunotherapy will help in improvement in outcome of

  3. Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

    Science.gov (United States)

    Tang, Jun; Chen, Qianwei; Guo, Jing; Yang, Liming; Tao, Yihao; Li, Lin; Miao, Hongping; Feng, Hua; Chen, Zhi; Zhu, Gang

    2016-04-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae. Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity. To test this hypothesis, the effects of minocycline and a CB2R antagonist (AM630) were evaluated in male rat pups that were post-natal day 7 (P7) after GMH. We found that minocycline can lead to increased CB2R mRNA expression and protein expression in microglia. Minocycline significantly reduced GMH-induced brain edema, microglial activation, and lateral ventricular volume. Additionally, minocycline enhanced cortical thickness after injury. All of these neuroprotective effects of minocycline were prevented by AM630. A cannabinoid CB2 agonist (JWH133) was used to strengthen the hypothesis, which showed the identical neuroprotective effects of minocycline. Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.

  4. Prediction of CT Substitutes from MR Images Based on Local Diffeomorphic Mapping for Brain PET Attenuation Correction.

    Science.gov (United States)

    Wu, Yao; Yang, Wei; Lu, Lijun; Lu, Zhentai; Zhong, Liming; Huang, Meiyan; Feng, Yanqiu; Feng, Qianjin; Chen, Wufan

    2016-10-01

    Attenuation correction is important for PET reconstruction. In PET/MR, MR intensities are not directly related to attenuation coefficients that are needed in PET imaging. The attenuation coefficient map can be derived from CT images. Therefore, prediction of CT substitutes from MR images is desired for attenuation correction in PET/MR. This study presents a patch-based method for CT prediction from MR images, generating attenuation maps for PET reconstruction. Because no global relation exists between MR and CT intensities, we propose local diffeomorphic mapping (LDM) for CT prediction. In LDM, we assume that MR and CT patches are located on 2 nonlinear manifolds, and the mapping from the MR manifold to the CT manifold approximates a diffeomorphism under a local constraint. Locality is important in LDM and is constrained by the following techniques. The first is local dictionary construction, wherein, for each patch in the testing MR image, a local search window is used to extract patches from training MR/CT pairs to construct MR and CT dictionaries. The k-nearest neighbors and an outlier detection strategy are then used to constrain the locality in MR and CT dictionaries. Second is local linear representation, wherein, local anchor embedding is used to solve MR dictionary coefficients when representing the MR testing sample. Under these local constraints, dictionary coefficients are linearly transferred from the MR manifold to the CT manifold and used to combine CT training samples to generate CT predictions. Our dataset contains 13 healthy subjects, each with T1- and T2-weighted MR and CT brain images. This method provides CT predictions with a mean absolute error of 110.1 Hounsfield units, Pearson linear correlation of 0.82, peak signal-to-noise ratio of 24.81 dB, and Dice in bone regions of 0.84 as compared with real CTs. CT substitute-based PET reconstruction has a regression slope of 1.0084 and R 2 of 0.9903 compared with real CT-based PET. In this method, no

  5. A clinical case of pseudotumorous chronic parainfectious limbic encephalitis

    Directory of Open Access Journals (Sweden)

    N. A. Shnaider

    2014-01-01

    Full Text Available Parainfectous limbic encephalitis (PILE associated with viruses of the Herpesviridae family is one of the forms of chronic herpes encephalitis characterized by limbic system dysfunction and a prolonged course with frequent exacerbations. There are two types of the course of the disease: latent autoimmune limbic encephalitis (LE progressing to mesial temporal sclerosis and pseudotumorous granulomatous LE. The latter (inflammatory pseudotumor or granuloma is characterized by the formation of a polymorphic inflammatory infiltrate with the elements of fibrosis, necrosis, and a granulomatous reaction and by myofibroblast cells. This is a slowly growing benign pseudotumor that contains much more plasma cells than inflammatory ones. The diagnosis of pseudotumorous LE is difficult and requires the participation of a neurologist, an immunologist, an oncologist, and a neurosurgeon. Perfusion computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy give proof to the adequacy of the term inflammatory pseudotumor because it is histologically difficult to characterize the lesion as a tumor or inflammation. When a chronic lesion in the central nervous system is lately diagnosed, the prognosis of the disease may be poor and complicated by the development of resistant symptomatic focal epilepsy and emotional, volitional, and cognitive impairments. It was differentially diagnosed from brain tumors (astrocytic, oligodendroglial, and mixed gliomas, ependymal, neuronal, neuroglial, and embryonal tumors, meningiomas, cholesteatomas, dermoid cysts, teratomas, and cysts, other reactive and inflammatory processes (leukemic infiltrations, systemic lupus erythematosus, multiple sclerosis, encephalomyelitis, hypoparathyroidism, Addison's disease, vitamin A intoxication, and the long-term use of glucocorticoids and contraceptives. The authors describe a clinical case of the pseudotumorous course of chronic PILE in a 28-year-old woman

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

    Directory of Open Access Journals (Sweden)

    Peng Fang

    Full Text Available 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.

  7. Attenuation of Oxidative Damage by Boerhaavia diffusa L. Against Different Neurotoxic Agents in Rat Brain Homogenate.

    Science.gov (United States)

    Ayyappan, Prathapan; Palayyan, Salin Raj; Kozhiparambil Gopalan, Raghu

    2016-01-01

    Due to a high rate of oxidative metabolic activity in the brain, intense production of reactive oxygen metabolite occurs, and the subsequent generation of free radicals is implicated in the pathogenesis of traumatic brain injury, epilepsy, and ischemia as well as chronic neurodegenerative diseases. In the present study, protective effects of polyphenol rich ethanolic extract of Boerhaavia diffusa (BDE), a neuroprotective edible medicinal plant against oxidative stress induced by different neurotoxic agents, were evaluated. BDE was tested against quinolinic acid (QA), 3-nitropropionic acid (NPA), sodium nitroprusside (SNP), and Fe (II)/EDTA complex induced oxidative stress in rat brain homogenates. QA, NPA, SNP, and Fe (II)/EDTA treatment caused an increased level of thiobarbituric acid reactive substances (TBARS) in brain homogenates along with a decline in the activities of antioxidant enzymes. BDE treatment significantly decreased the production of TBARS (p cerebral cortex. Inhibitory potential of BDE against deoxyribose degradation (IC50 value 38.91 ± 0.12 μg/ml) shows that BDE can protect hydroxyl radical induced DNA damage in the tissues. Therefore, B. diffusa had high antioxidant potential that could inhibit the oxidative stress induced by different neurotoxic agents in brain. Since many of the neurological disorders are associated with free radical injury, these data may imply that B. diffusa, functioning as an antioxidant agent, may be beneficial for reducing various neurodegenerative complications.

  8. Effect of scatter and attenuation correction in ROI analysis of brain perfusion scintigraphy. Phantom experiment and clinical study in patients with unilateral cerebrovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Bai, J. [Keio Univ., Tokyo (Japan). 21st Century Center of Excellence Program; Hashimoto, J.; Kubo, A. [Keio Univ., Tokyo (Japan). Dept. of Radiology; Ogawa, K. [Hosei Univ., Tokyo (Japan). Dept. of Electronic Informatics; Fukunaga, A.; Onozuka, S. [Keio Univ., Tokyo (Japan). Dept. of Neurosurgery

    2007-07-01

    The aim of this study was to evaluate the effect of scatter and attenuation correction in region of interest (ROI) analysis of brain perfusion single-photon emission tomography (SPECT), and to assess the influence of selecting the reference area on the calculation of lesion-to-reference count ratios. Patients, methods: Data were collected from a brain phantom and ten patients with unilateral internal carotid artery stenosis. A simultaneous emission and transmission scan was performed after injecting {sup 123}I-iodoamphetamine. We reconstructed three SPECT images from common projection data: with scatter correction and nonuniform attenuation correction, with scatter correction and uniform attenuation correction, and with uniform attenuation correction applied to data without scatter correction. Regional count ratios were calculated by using four different reference areas (contralateral intact side, ipsilateral cerebellum, whole brain and hemisphere). Results: Scatter correction improved the accuracy of measuring the count ratios in the phantom experiment. It also yielded marked difference in the count ratio in the clinical study when using the cerebellum, whole brain or hemisphere as the reference. Difference between nonuniform and uniform attenuation correction was not significant in the phantom and clinical studies except when the cerebellar reference was used. Calculation of the lesion-to-normal count ratios referring the same site in the contralateral hemisphere was not dependent on the use of scatter correction or transmission scan-based attenuation correction. Conclusion: Scatter correction was indispensable for accurate measurement in most of the ROI analyses. Nonuniform attenuation correction is not necessary when using the reference area other than the cerebellum. (orig.)

  9. Thymoquinone attenuates brain injury via an antioxidative pathway in a status epilepticus rat model

    Directory of Open Access Journals (Sweden)

    Shao Yi-ye

    2017-03-01

    Full Text Available Status epilepticus (SE results in the generation of reactive oxygen species (ROS, which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE. Thymoquinone (TQ is a bioactive monomer extracted from black cumin (Nigella sativa seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway.

  10. Specificity protein 1-zinc finger protein 179 pathway is involved in the attenuation of oxidative stress following brain injury

    Directory of Open Access Journals (Sweden)

    Jian-Ying Chuang

    2017-04-01

    Full Text Available After sudden traumatic brain injuries, secondary injuries may occur during the following days or weeks, which leads to the accumulation of reactive oxygen species (ROS. Since ROS exacerbate brain damage, it is important to protect neurons against their activity. Zinc finger protein 179 (Znf179 was shown to act as a neuroprotective factor, but the regulation of gene expression under oxidative stress remains unknown. In this study, we demonstrated an increase in Znf179 protein levels in both in vitro model of hydrogen peroxide (H2O2-induced ROS accumulation and animal models of traumatic brain injury. Additionally, we examined the sub-cellular localization of Znf179, and demonstrated that oxidative stress increases Znf179 nuclear shuttling and its interaction with specificity protein 1 (Sp1. Subsequently, the positive autoregulation of Znf179 expression, which is Sp1-dependent, was further demonstrated using luciferase reporter assay and green fluorescent protein (GFP-Znf179-expressing cells and transgenic mice. The upregulation of Sp1 transcriptional activity induced by the treatment with nerve growth factor (NGF led to an increase in Znf179 levels, which further protected cells against H2O2-induced damage. However, Sp1 inhibitor, mithramycin A, was shown to inhibit NGF effects, leading to a decrease in Znf179 expression and lower cellular protection. In conclusion, the results obtained in this study show that Znf179 autoregulation through Sp1-dependent mechanism plays an important role in neuroprotection, and NGF-induced Sp1 signaling may help attenuate more extensive (ROS-induced damage following brain injury.

  11. Cone-beam CT image contrast and attenuation-map linearity improvement (CALI) for brain stereotactic radiosurgery procedures

    Science.gov (United States)

    Hashemi, Sayed Masoud; Lee, Young; Eriksson, Markus; Nordström, Hâkan; Mainprize, James; Grouza, Vladimir; Huynh, Christopher; Sahgal, Arjun; Song, William Y.; Ruschin, Mark

    2017-03-01

    A Contrast and Attenuation-map (CT-number) Linearity Improvement (CALI) framework is proposed for cone-beam CT (CBCT) images used for brain stereotactic radiosurgery (SRS). The proposed framework is used together with our high spatial resolution iterative reconstruction algorithm and is tailored for the Leksell Gamma Knife ICON (Elekta, Stockholm, Sweden). The incorporated CBCT system in ICON facilitates frameless SRS planning and treatment delivery. The ICON employs a half-cone geometry to accommodate the existing treatment couch. This geometry increases the amount of artifacts and together with other physical imperfections causes image inhomogeneity and contrast reduction. Our proposed framework includes a preprocessing step, involving a shading and beam-hardening artifact correction, and a post-processing step to correct the dome/capping artifact caused by the spatial variations in x-ray energy generated by bowtie-filter. Our shading correction algorithm relies solely on the acquired projection images (i.e. no prior information required) and utilizes filtered-back-projection (FBP) reconstructed images to generate a segmented bone and soft-tissue map. Ideal projections are estimated from the segmented images and a smoothed version of the difference between the ideal and measured projections is used in correction. The proposed beam-hardening and dome artifact corrections are segmentation free. The CALI was tested on CatPhan, as well as patient images acquired on the ICON system. The resulting clinical brain images show substantial improvements in soft contrast visibility, revealing structures such as ventricles and lesions which were otherwise un-detectable in FBP-reconstructed images. The linearity of the reconstructed attenuation-map was also improved, resulting in more accurate CT#.

  12. Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

    Science.gov (United States)

    C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

    2014-12-01

    3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

  13. Brain and Addiction

    Science.gov (United States)

    ... reward” circuit, which is part of the limbic system. Normally, the reward circuit responds to feelings of pleasure by releasing ... infographic, discover how drug use affects the brain's reward system. This publication is available for your use and ...

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

    Science.gov (United States)

    Rolls, Edmund T

    2015-01-01

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

  15. MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell Activation in the Brain.

    Science.gov (United States)

    Kip, E; Staal, J; Verstrepen, L; Tima, H G; Terryn, S; Romano, M; Lemeire, K; Suin, V; Hamouda, A; Kalai, M; Beyaert, R; Van Gucht, S

    2018-04-15

    MALT1 is involved in the activation of immune responses, as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target. Although MALT1 deficiency has been shown to protect against experimental autoimmune encephalomyelitis, nothing is known about the impact of MALT1 on virus infection in the central nervous system. Here, we studied infection with an attenuated rabies virus, Evelyn-Rotnycki-Abelseth (ERA) virus, and observed increased susceptibility with ERA virus in MALT1 -/- mice. Indeed, after intranasal infection with ERA virus, wild-type mice developed mild transient clinical signs with recovery at 35 days postinoculation (dpi). Interestingly, MALT1 -/- mice developed severe disease requiring euthanasia at around 17 dpi. A decreased induction of inflammatory gene expression and cell infiltration and activation was observed in MALT1 -/- mice at 10 dpi compared to MALT1 +/+ infected mice. At 17 dpi, however, the level of inflammatory cell activation was comparable to that observed in MALT1 +/+ mice. Moreover, MALT1 -/- mice failed to produce virus-neutralizing antibodies. Similar results were obtained with specific inactivation of MALT1 in T cells. Finally, treatment of wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality upon ERA virus infection. These data emphasize the importance of early inflammation and activation of T cells through MALT1 for controlling the virulence of an attenuated rabies virus in the brain. IMPORTANCE Rabies virus is a neurotropic virus which can infect any mammal. Annually, 59,000 people die from rabies. Effective therapy is lacking and hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular

  16. MR-guided joint reconstruction of activity and attenuation in brain PET-MR

    DEFF Research Database (Denmark)

    Mehranian, Abolfazl; Zaidi, Habib; Reader, Andrew J

    2017-01-01

    by unknown scaling factors. We recently demonstrated that in hybrid PET-MR, the scaling issue of this algorithm can be effectively addressed by imposing MR spatial constraints on the estimation of attenuation maps using a penalized MLAA (P-MLAA(+)) algorithm. With the advent of simultaneous PET-MR systems......, MRI-guided PET image reconstruction has also gained attention for improving the quantitative accuracy of PET images, usually degraded by noise and partial volume effects. The aim of this study is therefore to increase the benefits of MRI information for improving the quantitative accuracy of PET...... as a reference. The simulation results showed that the proposed method can notably improve the visual quality of the PET images by reducing noise while preserving structural boundaries and at the same time improving the quantitative accuracy of the PET images. Our clinical reconstruction results showed...

  17. Alexithymia is associated with attenuated automatic brain response to facial emotion in clinical depression.

    Science.gov (United States)

    Suslow, Thomas; Kugel, Harald; Rufer, Michael; Redlich, Ronny; Dohm, Katharina; Grotegerd, Dominik; Zaremba, Dario; Dannlowski, Udo

    2016-02-04

    Alexithymia is a clinically relevant personality trait related to difficulties in recognizing and describing emotions. Previous studies examining the neural correlates of alexithymia have shown mainly decreased response of several brain areas during emotion processing in healthy samples and patients suffering from autism or post-traumatic stress disorder. In the present study, we examined the effect of alexithymia on automatic brain reactivity to negative and positive facial expressions in clinical depression. Brain activation in response to sad, happy, neutral, and no facial expression (presented for 33 ms and masked by neutral faces) was measured by functional magnetic resonance imaging at 3 T in 26 alexithymic and 26 non-alexithymic patients with major depression. Alexithymic patients manifested less activation in response to masked sad and happy (compared to neutral) faces in right frontal regions and right caudate nuclei than non-alexithymic patients. Our neuroimaging study provides evidence that the personality trait alexithymia has a modulating effect on automatic emotion processing in clinical depression. Our findings support the idea that alexithymia could be associated with functional deficits of the right hemisphere. Future research on the neural substrates of emotion processing in depression should assess and control alexithymia in their analyses.

  18. Autism attenuates sex differences in brain structure: a combined voxel-based morphometry and diffusion tensor imaging study.

    Science.gov (United States)

    Beacher, F D; Minati, L; Baron-Cohen, S; Lombardo, M V; Lai, M-C; Gray, M A; Harrison, N A; Critchley, H D

    2012-01-01

    It has been proposed that autism spectrums condition may represent a form of extreme male brain (EMB), a notion supported by psychometric, behavioral, and endocrine evidence. Yet, limited data are presently available evaluating this hypothesis in terms of neuroanatomy. Here, we investigated sex-related anatomic features in adults with AS, a "pure" form of autism not involving major developmental delay. Males and females with AS and healthy controls (n = 28 and 30, respectively) were recruited. Structural MR imaging was performed to measure overall gray and white matter volume and to assess regional effects by means of VBM. DTI was used to investigate the integrity of the main white matter tracts. Significant interactions were found between sex and diagnosis in total white matter volume, regional gray matter volume in the right parietal operculum, and fractional anisotropy (FA) in the body of the CC, cingulum, and CR. Post hoc comparisons indicated that the typical sexual dimorphism found in controls, whereby males have larger FA and total white matter volume, was absent or attenuated in participants with AS. Our results point to a fundamental role of the factors that underlie sex-specific brain differentiation in the etiology of autism.

  19. Effects of attenuation and scatter corrections in cat brain PET images using microPET R4 scanner

    International Nuclear Information System (INIS)

    Kim, Jin Su; Lee, Jae Sung; Lee, Jong Jin

    2006-01-01

    The aim of this study was to examine the effects of attenuation correction (AC) and scatter correction (SC) on the quantification of PET count rates. To assess the effects of AC and SC, 18 F-FDG PET images of phantom and cat brain were acquired using microPET R4 scanner. Thirty-minute transmission images using 68 Ge source and emission images after injection of FDG were acquired. PET images were reconstructed using. 2D OSEM. AC and SC were applied. Regional count rates were measured using ROls drawn on cerebral cortex including frontal, parietal, and latral temporal lobes and deep gray matter including head of caudate nucleus, putamen and thalamus for pre- and post-AC and SC images. The count rates were then normalized with the injected dose per body weight. To assess the effects of AC, count ratio of 'deep gray matter/cerebral cortex' was calculated. To assess the effects of SC, ROls were also drawn on the gray matter (GM) and white matter (WM), and contrast between them ((GM-WM)/GM) was measured. After the AC, count ratio of 'deep gray matter/cerebral cortex' was increased by 17±7%. After the SC, contrast was also increased by 12±3%. Relative count of deep gray matter and contrast between gray and white matters were increased after AC and SC, suggesting that the AC would be critical for the quantitative analysis of cat brain PET data

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

    Science.gov (United States)

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

    2016-03-01

    white matter across various regions of the brain. In contrast to this, the inflammatory process seems to be more localized in VGKC-complex-associated limbic encephalitis, primarily affecting mesiotemporal gray matter. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  1. Cofilin Knockdown Attenuates Hemorrhagic Brain Injury-induced Oxidative Stress and Microglial Activation in Mice.

    Science.gov (United States)

    Alhadidi, Qasim; Nash, Kevin M; Alaqel, Saleh; Sayeed, Muhammad Shahdaat Bin; Shah, Zahoor A

    2018-05-08

    Intracerebral hemorrhage (ICH) resulting from the rupture of the blood vessels in the brain is associated with significantly higher mortality and morbidity. Clinical studies focused on alleviating the primary injury, hematoma formation and expansion, were largely ineffective, suggesting that secondary injury-induced inflammation and the formation of reactive species also contribute to the overall injury process. In this study, we explored the effects of cofilin knockdown in a mouse model of ICH. Animals given stereotaxic injections of cofilin siRNA, 72-h prior to induction of ICH by collagenase injection within the area of siRNA administration showed significantly decreased cofilin expression levels and lower hemorrhage volume and edema, and the animals performed significantly better in neurobehavioral tasks i.e., rotarod, grip strength and neurologic deficit scores. Cofilin siRNA knocked-down mice had reduced ICH-induced DNA fragmentation, blood-brain barrier disruption and microglial activation, with a concomitant increase in astrocyte activation. Increased expression of pro-survival proteins and decreased markers of oxidative stress were also observed in cofilin siRNA-treated mice possibly due to the reduced levels of cofilin. Our results suggest that cofilin plays a major role in ICH-induced secondary injury, and could become a potential therapeutic target. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Neuronal surface antigen antibodies in limbic encephalitis

    Science.gov (United States)

    Graus, F; Saiz, A; Lai, M; Bruna, J; López, F; Sabater, L; Blanco, Y; Rey, M J.; Ribalta, T; Dalmau, J

    2008-01-01

    Objective: To report the frequency and type of antibodies against neuronal surface antigens (NSA-ab) in limbic encephalitis (LE). Methods: Analysis of clinical features, neuropathologic findings, and detection of NSA-ab using immunochemistry on rat tissue and neuronal cultures in a series of 45 patients with paraneoplastic (23) or idiopathic (22) LE. Results: NSA-ab were identified in 29 patients (64%; 12 paraneoplastic, 17 idiopathic). Thirteen patients had voltage-gated potassium channels (VGKC)-ab, 11 novel NSA (nNSA)-ab, and 5 NMDA receptor (NMDAR)-ab. nNSA-ab did not identify a common antigen and were more frequent in paraneoplastic than idiopathic LE (39% vs 9%; p = 0.03). When compared with VGKC-ab or NMDAR-ab, the nNSA associated more frequently with intraneuronal antibodies (11% vs 73%; p = 0.001). Of 12 patients (9 nNSA-ab, 2 VGKC-ab, 1 NMDAR-ab) with paraneoplastic LE and NSA-ab, concomitant intraneuronal antibodies occurred in 9 (75%). None of these 12 patients improved with immunotherapy. The autopsy of three of them showed neuronal loss, microgliosis, and cytotoxic T cell infiltrates in the hippocampus and amygdala. These findings were compatible with a T-cell mediated neuronal damage. In contrast, 13 of 17 (76%) patients with idiopathic LE and NSA-ab (8 VGKC-ab, 4 NMDAR-ab, 1 nNSA-ab) and 1 of 5 (20%) without antibodies had clinical improvement (p = 0.04). Conclusions: In paraneoplastic limbic encephalitis (LE), novel antibodies against neuronal surface antigens (nNSA-ab) occur frequently, coexist with antibodies against intracellular antigens, and these cases are refractory to immunotherapy. In idiopathic LE, the likelihood of improvement is significantly higher in patients with NSA-ab than in those without antibodies. GLOSSARY GAD = glutamic acid decarboxylase; LE = limbic encephalitis; NMDAR = N-methyl-D-aspartate receptor; NSA = neuronal surface antigens; nNSA = novel NSA; SCLC = small-cell lung cancer; VGKC = voltage-gated potassium channels

  3. Paraneoplastic limbic encephalitis with associated hypothalamitis mimicking a hyperdense hypothalamic tumor: a case report

    International Nuclear Information System (INIS)

    Bataduwaarachchi, Vipula R.; Tissera, Nirmali

    2016-01-01

    Paraneoplastic limbic encephalitis is an uncommon association of common malignancies such as small cell lung carcinoma, testicular teratoma, and breast carcinoma. The nonspecific nature of the clinical presentation, lack of freely available diagnostic markers, and requirement for advanced imaging techniques pose a great challenge in the diagnosis of this disease in resource-poor settings. A 64-year-old previously healthy Sri Lankan man was admitted to the general medical unit with subacute memory impairment regarding recent events that had occurred during the previous 3 weeks. Initial noncontrast computed tomography of the brain revealed a hyperdensity in the hypothalamic region surrounded by hypodensities extending toward the bilateral temporal lobes; these findings were consistent with a possible hypothalamic tumor with perilesional edema. The patient later developed cranial diabetes insipidus, which was further suggestive of hypothalamic disease. Interestingly, gadolinium-enhanced magnetic resonance imaging of the brain showed no such lesions; instead, it showed prominent T2-weighted signals in the inner mesial region, characteristic of encephalitis. The possibility of tuberculosis and viral encephalitis was excluded based on cerebrospinal fluid analysis results. Limbic encephalitis with predominant hypothalamitis was suspected based on the radiological pattern. Subsequent screening for underlying malignancy revealed a mass lesion in the right hilum on chest radiographs. Histological examination of the lesion showed small cell lung cancer of the “oat cell” variety. We suggest that the initial appearance of a hyperdensity in the hypothalamus region on noncontrast computed tomography is probably due to hyperemia caused by hypothalamitis. If hypothalamitis is predominant in a patient with paraneoplastic limbic encephalitis, magnetic resonance imaging will help to differentiate it from a hypothalamic secondary deposit. Limbic encephalitis should be considered in

  4. Propolis attenuates oxidative injury in brain and lung of nitric oxide synthase inhibited rats

    Directory of Open Access Journals (Sweden)

    Zeliha Selamoglu-Talas

    2015-10-01

    Full Text Available Background: The blocking of nitric oxide synthase (NOS activity may reason vasoconstriction with formation of reactive oxygen species. Propolis has biological and pharmacological properties, such as antioxidant. The aim of this study was to examine the antioxidant effects of propolis which natural product on biochemical parameters in brain and lung tissues of acute nitric oxide synthase inhibited rats by Nω-nitro-L-arginine methyl ester (L-NAME.Methods: Rats have been received L-NAME (40 mg/kg, intraperitoneally, NOS inhibitor for 15 days to produce hypertension and propolis (200mg/kg, by gavage the lastest 5 of 15 days.Results: There  were  the  increase  (P<0.001  in  the  malondialdehyde  levels  in  the  L-NAME treatment groups when compared to control rats, but the decrease (P<0.001 in the catalase activities in both brain and lung tissues. There were statistically changes (P<0.001 in these parameters of L-NAME+propolis treated rats as compared with L-NAME-treated group.Conclusion: The application of L-NAME to the Wistar rats resulted in well developed oxidative stress. Also, propolis may influence endothelial NO production. Identification of such compounds and characterisation of their cellular actions may increase our knowledge of the regulation of endothelial NO production and could provide valuable clues for the prevention or treatment of hypertensive diseases and oxidative stress.

  5. Ivy Sign on Fluid-Attenuated Inversion Recovery Images in Moyamoya Disease: Correlation with Clinical Severity and Old Brain Lesions.

    Science.gov (United States)

    Seo, Kwon-Duk; Suh, Sang Hyun; Kim, Yong Bae; Kim, Ji Hwa; Ahn, Sung Jun; Kim, Dong-Seok; Lee, Kyung-Yul

    2015-09-01

    Leptomeningeal collateral, in moyamoya disease (MMD), appears as an ivy sign on fluid-attenuated inversion-recovery (FLAIR) images. There has been little investigation into the relationship between presentation of ivy signs and old brain lesions. We aimed to evaluate clinical significance of ivy signs and whether they correlate with old brain lesions and the severity of clinical symptoms in patients with MMD. FLAIR images of 83 patients were reviewed. Each cerebral hemisphere was divided into 4 regions and each region was scored based on the prominence of the ivy sign. Total ivy score (TIS) was defined as the sum of the scores from the eight regions and dominant hemispheric ivy sign (DHI) was determined by comparing the ivy scores from each hemisphere. According to the degree of ischemic symptoms, patients were classified into four subgroups: 1) nonspecific symptoms without motor weakness, 2) single transient ischemic attack (TIA), 3) recurrent TIA, or 4) complete stroke. TIS was significantly different as follows: 4.86±2.55 in patients with nonspecific symptoms, 5.89±3.10 in patients with single TIA, 9.60±3.98 in patients with recurrent TIA and 8.37±3.39 in patients with complete stroke (p=0.003). TIS associated with old lesions was significantly higher than those not associated with old lesions (9.35±4.22 vs. 7.49±3.37, p=0.032). We found a significant correlation between DHI and motor symptoms (p=0.001). Because TIS has a strong tendency with severity of ischemic motor symptom and the presence of old lesions, the ivy sign may be useful in predicting severity of disease progression.

  6. A case of limbic encephalitis presenting as a paraneoplastic manifestation of limited stage small cell lung cancer: a case report

    Directory of Open Access Journals (Sweden)

    Butt Mohammad

    2010-12-01

    Full Text Available Abstract Introduction The differential diagnosis of altered mental status and behavioral change is very extensive. Paraneoplastic limbic encephalitis is a rare cause of cognitive impairment, which should be considered in the differential diagnosis. Case presentation A 64-year-old British Caucasian woman presented to our hospital with a 12-week history of confusion and short-term memory loss. She was hyponatremic with a serum sodium level of 128mmol/L. Moreover, there was evidence of left hilar prominence on the chest radiograph. A thoracic computed tomography scan showed left hilar opacity with confluent lymphadenopathy. A percutaneous biopsy confirmed a diagnosis of small cell lung cancer. There was no radiological evidence of brain metastasis on the computed tomography scan. In view of continued cognitive impairment, which was felt to be disproportionate to hyponatremia, a magnetic resonance imaging scan of the brain was undertaken. It showed hyperintense signals from both hippocampi, highly suggestive of limbic encephalitis presenting as a paraneoplastic manifestation of small cell lung cancer. She had a significant radiological and clinical response following chemotherapy and radiotherapy. Conclusion This case highlights the importance of considering paraneoplastic syndromes in patients with neurological symptoms in the context of lung malignancy. If initial investigations fail to reveal the cause of cognitive impairment in a patient with malignancy, magnetic resonance imaging may be invaluable in the diagnosis of limbic encephalitis. The clinical presentation, diagnostic techniques and management of paraneoplastic limbic encephalitis are discussed in this case report.

  7. Fatty acid-induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans.

    Science.gov (United States)

    Van Oudenhove, Lukas; McKie, Shane; Lassman, Daniel; Uddin, Bilal; Paine, Peter; Coen, Steven; Gregory, Lloyd; Tack, Jan; Aziz, Qasim

    2011-08-01

    Although a relationship between emotional state and feeding behavior is known to exist, the interactions between signaling initiated by stimuli in the gut and exteroceptively generated emotions remain incompletely understood. Here, we investigated the interaction between nutrient-induced gut-brain signaling and sad emotion induced by musical and visual cues at the behavioral and neural level in healthy nonobese subjects undergoing functional magnetic resonance imaging. Subjects received an intragastric infusion of fatty acid solution or saline during neutral or sad emotion induction and rated sensations of hunger, fullness, and mood. We found an interaction between fatty acid infusion and emotion induction both in the behavioral readouts (hunger, mood) and at the level of neural activity in multiple pre-hypothesized regions of interest. Specifically, the behavioral and neural responses to sad emotion induction were attenuated by fatty acid infusion. These findings increase our understanding of the interplay among emotions, hunger, food intake, and meal-induced sensations in health, which may have important implications for a wide range of disorders, including obesity, eating disorders, and depression.

  8. Repetitive Hyperbaric Oxygenation Attenuates Reactive Astrogliosis and Suppresses Expression of Inflammatory Mediators in the Rat Model of Brain Injury

    Directory of Open Access Journals (Sweden)

    Irena Lavrnja

    2015-01-01

    Full Text Available The exact mechanisms by which treatment with hyperbaric oxygen (HBOT exerts its beneficial effects on recovery after brain injury are still unrevealed. Therefore, in this study we investigated the influence of repetitive HBOT on the reactive astrogliosis and expression of mediators of inflammation after cortical stab injury (CSI. CSI was performed on male Wistar rats, divided into control, sham, and lesioned groups with appropriate HBO. The HBOT protocol was as follows: 10 minutes of slow compression, 2.5 atmospheres absolute (ATA for 60 minutes, and 10 minutes of slow decompression, once a day for 10 consecutive days. Data obtained using real-time polymerase chain reaction, Western blot, and immunohistochemical and immunofluorescence analyses revealed that repetitive HBOT applied after the CSI attenuates reactive astrogliosis and glial scarring, and reduces expression of GFAP (glial fibrillary acidic protein, vimentin, and ICAM-1 (intercellular adhesion molecule-1 both at gene and tissue levels. In addition, HBOT prevents expression of CD40 and its ligand CD40L on microglia, neutrophils, cortical neurons, and reactive astrocytes. Accordingly, repetitive HBOT, by prevention of glial scarring and limiting of expression of inflammatory mediators, supports formation of more permissive environment for repair and regeneration.

  9. Autoimmune neurological syndromes associated limbic encephalitis and paraneoplastic cerebellar degeneration.

    Science.gov (United States)

    Ayas, Zeynep Özözen; Kotan, Dilcan; Aras, Yeşim Güzey

    2016-10-06

    Autoimmune neurological syndrome is a group of disorders caused by cancer affecting nervous system by different immunological mechanisms. In this study, we aim to study the clinical symptoms, cerebrospinal fluid (CSF) findings, autoantibody tests, computed tomography (CT), magnetic resonance imaging (MRI) signs and treatment outcome of patients with autoimmune syndromes. In this study, 7 patients (4 male, 3 female) diagnosed with autoimmune neurological syndrome were retrospectively examined. Five of patients were diagnosed with limbic encephalitis, two of them were paraneoplastic cerebellar degeneration. Confusion and seizure were the most seen symptoms. Two patients had psychiatric disturbances (28,5%) followed by seizure. Headache was seen in 2 patients (% 28,5), disartria in 1 patient (% 14,2), and gait disorder in 2 patients (28,5%). The duration of symptoms was 46 (3-150) days on average. CSF abnormalities were detected in 2 patients. CT and MRI of the brain was available in all patients. Five patients had involvement of mesiotemporal region, two patients had diffuse cerebellar atrophy. One of patients had anti-GABAR B1 positivity. Tumors were detected in 2 patients while investigation for paraneoplasia screening. Remission is only possible with the detection and treatment of the malignancy. Early diagnosis and treatment are of paramount importance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Paraneoplastic limbic encephalitis in a teenage girl with an immature ovarian teratoma

    International Nuclear Information System (INIS)

    Stein-Wexler, Rebecca; Wootton-Gorges, Sandra L.; Brunberg, James A.; Greco, Claudia M.

    2005-01-01

    Paraneoplastic limbic encephalitis (PLE) is an unusual disorder that is characterized by the association of clinical limbic system abnormalities with neoplasia, usually malignancy. It has rarely been reported in children and then manifests during the teenage years. Diagnosis is often delayed, especially when the tumor has not been recognized. In adults, the diagnosis can be revealed by the presence of antineuronal antibodies. We describe an unusual case of behavioral disturbance leading rapidly to coma in a 14-year-old girl with CSF pleocytosis who was found 10 weeks later to have an immature ovarian teratoma. Although her symptoms eventually improved slightly after tumor excision, she died while in rehabilitation. PLE is an important diagnosis to consider in the teenage girl with symptoms of a progressive limbic disorder and CSF pleocytosis, and whose brain MR imaging demonstrates no abnormality or mild T2-weighted temporal lobe signal abnormality. When this constellation of findings presents in a teenage girl, the possibility of an underlying ovarian teratoma should be considered. (orig.)

  11. Limbic Encephalitis Driven by a Pleural Mesothelioma: A Paraneoplastic Complication

    Directory of Open Access Journals (Sweden)

    Jacob O. Day

    2016-10-01

    Full Text Available Paraneoplastic neurological syndromes have only been described with pleural mesothelioma in five cases. We have described a 72-year-old man who developed anterograde amnesia 27 months after diagnosis of epithelioid pleural mesothelioma. Investigations revealed a limbic encephalitis with no alternative causes identified. Limbic encephalitis is a classical paraneoplastic syndrome and presentation within five years of a cancer with no other causes identified is sufficient to diagnose a paraneoplastic etiology. This is the first case of isolated paraneoplastic limbic encephalitis driven by a pleural mesothelioma.

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

    Science.gov (United States)

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

    2015-02-18

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

  13. Assessment of Radiation-Attenuated Vaccine or Thyme Oil Treatment on Controlling DNA Damage and Nitric Oxide Synthesis in Brain of Rat Infected with Toxocara canis

    International Nuclear Information System (INIS)

    Amin, M.M.; Hafez, E.N.; Abd Raboo, M.A.

    2016-01-01

    Toxocara canis is a worldwide zoonotic roundworm that infects a number of hosts including humans. It exhibits marked affinity to the nervous tissues. This study deals with the changes in the brain of Toxocara canis infected rats regarding parasitological, nitric oxide (NO) level and DNA damage compared to the effect of vaccination with gamma radiation-attenuated embryonated egg or thyme oil treatment. Eighty rats were classified into four groups (twenty each): GI (normal control); GII infected with 2500 T. canis infective eggs/ml/rat (infected control); GIII vaccinated with 800 Gy gamma-attenuated embryonated eggs (vaccinated group) and GIV infected with 2500 T. canis eggs and treated with thyme oil (thyme treated group). At the 14th day post-infection, ten rats from each group were sacrificed and the remaining were re-infected (challenged) with the same number of eggs. At the 14th days post challenge, brain tissues were taken for larval recovery, nitric oxide level evaluation and DNA damage using fragmentation and comet assay. The results exhibited a significant decrease in larval count and nitric oxide level with less damage in brain cells in thyme treated and gamma radiation-attenuated vaccinated groups compared to control infected group. It is also, concluded that vaccination using γ- rays is more effective in protection compared to using thyme oil.

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

    Science.gov (United States)

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

    2013-09-01

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

  15. Liquid nitrogen cryotherapy of superior limbic keratoconjunctivitis.

    Science.gov (United States)

    Fraunfelder, Frederick W

    2009-02-01

    To evaluate the effects of liquid nitrogen cryotherapy on superior limbic keratoconjunctivitis (SLK). Interventional case series. In this clinical practice case series, the effects of liquid nitrogen cryotherapy on SLK were observed. Liquid nitrogen cryotherapy was performed using a Brymill E tip spray (0.013-inch aperture) with a double freeze-thaw technique. All subjects were outpatients who had local anesthesia with a single drop of topical proparacaine. The main outcome measure was the resolution of the disease process after treatment. Four female patients (average age, 64 +/- 13 years) and seven eyes with SLK were treated with liquid nitrogen cryotherapy. Resolution of signs and symptoms occurred within two weeks. Disease recurred in two patients and three of seven eyes, although repeat cryotherapy eradicated SLK in all cases. The repeat cryotherapy was performed at three months postoperatively. There were no adverse ocular events. Liquid nitrogen cryotherapy appears to be an effective alternative treatment for SLK as all subjects studied achieved long-term cures. Repeat cryotherapy may be necessary in some instances and may be performed three months after the first treatment.

  16. Cerebral activation associated with visually evoked sexual arousal in the limbic system: functional MR imaging

    International Nuclear Information System (INIS)

    Eun, Sung Jong; Kong, Gwang Woo; Kim, Hyung Joong; Seo, Jeong Jin; Kang, Heoung Keun; Cho, Ki Hyun; Yoon, Ka Hyun; Kim, Kyung Yo

    2004-01-01

    To identify the brain centers associated with visually evoked sexual arousal in the human brain, and to investigate the neural mechanism for sexual arousal using functional MRI (fMRI). A total of 20 sexually potent volunteers consisting of 10 males (mean age: 24) and 10 females (mean age: 23) underwent fMRI on a 1.5T MR scanner (GE Signa Horizon). The fMRI data were obtained from 7 slices (10 mm slice thickness) parallel to the AC-PC (anterior commissure and posterior commissure) line, giving a total of 511 MR images. The sexual stimulation consisted of a 1-minute rest with black screen, followed by a 4-minute stimulation by an erotic video film, and concluded with a 2-minute rest. The brain activation maps and their quantification were analyzed by the statistical parametric mapping (SPM 99) program. The brain activation regions associated with visual sexual arousal in the limbic system are the posterior cingulate gyrus, parahippocampal gyrus, hypothalamus, medial cingulate gyrus, thalamus, amygdala, anterior cingulate gyrus, insula, hippocampus, caudate nucleus, globus pallidus and putamen. Especially, the parahippocampal gyrus, cingulate gyrus, thalamus and hypothalamus were highly activated in comparison with other areas. The overall activities of the limbic lobe, diencephalon, and basal ganglia were 11.8%, 10.5%, and 3.4%, respectively. In the correlation test between brain activity and sexual arousal, the hypothalamus and thalamus showed positive correlation, but the other brain areas showed no correlation. The fMRI is useful to quantitatively evaluate the cerebral activation associated with visually evoked, sexual arousal in the human brain. This result may be helpful by providing clinically valuable information on sexual disorder in humans as well as by increasing the understanding of the neuroanatomical correlates of sexual arousal

  17. Cerebral activation associated with visually evoked sexual arousal in the limbic system: functional MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Eun, Sung Jong; Kong, Gwang Woo; Kim, Hyung Joong; Seo, Jeong Jin; Kang, Heoung Keun; Cho, Ki Hyun; Yoon, Ka Hyun [School of Medicine, Chonnam National Univ., Kwangju (Korea, Republic of); Kim, Kyung Yo [Wonkwang Univ., Iksan (Korea, Republic of)

    2004-08-01

    To identify the brain centers associated with visually evoked sexual arousal in the human brain, and to investigate the neural mechanism for sexual arousal using functional MRI (fMRI). A total of 20 sexually potent volunteers consisting of 10 males (mean age: 24) and 10 females (mean age: 23) underwent fMRI on a 1.5T MR scanner (GE Signa Horizon). The fMRI data were obtained from 7 slices (10 mm slice thickness) parallel to the AC-PC (anterior commissure and posterior commissure) line, giving a total of 511 MR images. The sexual stimulation consisted of a 1-minute rest with black screen, followed by a 4-minute stimulation by an erotic video film, and concluded with a 2-minute rest. The brain activation maps and their quantification were analyzed by the statistical parametric mapping (SPM 99) program. The brain activation regions associated with visual sexual arousal in the limbic system are the posterior cingulate gyrus, parahippocampal gyrus, hypothalamus, medial cingulate gyrus, thalamus, amygdala, anterior cingulate gyrus, insula, hippocampus, caudate nucleus, globus pallidus and putamen. Especially, the parahippocampal gyrus, cingulate gyrus, thalamus and hypothalamus were highly activated in comparison with other areas. The overall activities of the limbic lobe, diencephalon, and basal ganglia were 11.8%, 10.5%, and 3.4%, respectively. In the correlation test between brain activity and sexual arousal, the hypothalamus and thalamus showed positive correlation, but the other brain areas showed no correlation. The fMRI is useful to quantitatively evaluate the cerebral activation associated with visually evoked, sexual arousal in the human brain. This result may be helpful by providing clinically valuable information on sexual disorder in humans as well as by increasing the understanding of the neuroanatomical correlates of sexual arousal.

  18. Sex differences of gray matter morphology in cortico-limbic-striatal neural system in major depressive disorder.

    Science.gov (United States)

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

    2013-06-01

    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 analyzes 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 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Polydatin attenuates d-galactose-induced liver and brain damage through its anti-oxidative, anti-inflammatory and anti-apoptotic effects in mice.

    Science.gov (United States)

    Xu, Lie-Qiang; Xie, You-Liang; Gui, Shu-Hua; Zhang, Xie; Mo, Zhi-Zhun; Sun, Chao-Yue; Li, Cai-Lan; Luo, Dan-Dan; Zhang, Zhen-Biao; Su, Zi-Ren; Xie, Jian-Hui

    2016-11-09

    Accumulating evidence has shown that chronic injection of d-galactose (d-gal) can mimic natural aging, with accompanying liver and brain injury. Oxidative stress and apoptosis play a vital role in the aging process. In this study, the antioxidant ability of polydatin (PD) was investigated using four established in vitro systems. An in vivo study was also conducted to investigate the possible protective effect of PD on d-gal-induced liver and brain damage. The results showed that PD had remarkable in vitro free radical scavenging activity on 2,2-diphenyl-1-picryl-hydrazyl (DPPH˙), 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) (ABTS + ˙) radical ions, and hydroxyl and superoxide anions. Results in vivo indicated that, in a group treated with d-gal plus PD, PD remarkably decreased the depression of body weight and organ indexes, reduced the levels of the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and alleviated alterations in liver and brain histopathology. PD also significantly decreased the level of MDA and elevated SOD, GSH-Px, CAT activity and T-AOC levels in the liver and brain. In addition, the levels of inflammatory mediators, such as TNF-α, IL-1β and IL-6 in serum were markedly reduced after PD treatment. Western blotting results revealed that PD treatment noticeably attenuated the d-gal-induced elevation of Bcl-2/Bax ratio and caspase-3 protein expression in liver and brain. Overall, our findings indicate that PD treatment could effectively attenuate d-gal-induced liver and brain damage, and the mechanism might be associated with decreasing the oxidative stress, inflammation and apoptosis caused by d-gal. PD holds good potential for further development into a promising pharmaceutical candidate for the treatment of age-associated diseases.

  20. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis.

    Science.gov (United States)

    Miller, Thomas D; Chong, Trevor T-J; Aimola Davies, Anne M; Ng, Tammy W C; Johnson, Michael R; Irani, Sarosh R; Vincent, Angela; Husain, Masud; Jacob, Saiju; Maddison, Paul; Kennard, Christopher; Gowland, Penny A; Rosenthal, Clive R

    2017-05-01

    Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P 3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  1. Furoxans (oxadiazole-4N-oxides) with Attenuated Reactivity are Neuroprotective, Cross the Blood Brain Barrier, and Improve Passive Avoidance Memory.

    Science.gov (United States)

    Horton, Austin; Nash, Kevin; Tackie-Yarboi, Ethel; Kostrevski, Alexander; Novak, Adam; Raghavan, Aparna; Tulsulkar, Jatin; Alhadidi, Qasim; Wamer, Nathan; Langenderfer, Bryn; Royster, Kalee; Ducharme, Maxwell; Hagood, Katelyn; Post, Megan; Shah, Zahoor A; Schiefer, Isaac T

    2018-04-23

    Nitric oxide (NO) mimetics and other agents capable of enhancing NO/cGMP signaling have demonstrated efficacy as potential therapies for Alzheimer's disease. A group of thiol-dependent NO mimetics known as furoxans may be designed to exhibit attenuated reactivity to provide slow onset NO effects. The present study describes the design, synthesis, and evaluation of a furoxan library resulting in the identification of a prototype furoxan, 5a, which was profiled for use in the CNS. 5a demonstrated negligible reactivity toward generic cellular thiols under physiological conditions. Nonetheless, cGMP dependent neuroprotection was observed. 5a (20 mg/kg) reversed cholinergic memory deficits in a mouse model of passive avoidance fear memory. Importantly, 5a can be prepared as a pharmaceutically acceptable salt and is observed in the brain 12 hr after oral administration, suggesting potential for daily dosing and excellent metabolic stability. Continued investigation into furoxans as attenuated NO mimetics for the CNS is warranted.

  2. Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− Mice

    Directory of Open Access Journals (Sweden)

    Sandro M. Krieg

    2017-08-01

    Full Text Available Danger-associated molecular patterns are released by damaged cells and trigger neuroinflammation through activation of non-specific pattern recognition receptors, e.g., toll-like receptors (TLRs. Since the role of TLR2 and 4 after traumatic brain injury (TBI is still unclear, we examined the outcome and the expression of pro-inflammatory mediators after experimental TBI in Tlr2/4−/− and wild-type (WT mice. Tlr2/4−/− and WT mice were subjected to controlled cortical injury and contusion volume and brain edema formation were assessed 24 h thereafter. Expression of inflammatory markers in brain tissue was measured by quantitative PCR 15 min, 3 h, 6 h, 12 h, and 24 h after controlled cortical impact (CCI. Contusion volume was significantly attenuated in Tlr2/4−/− mice (29.7 ± 0.7 mm3 as compared to 33.5 ± 0.8 mm3 in WT; p < 0.05 after CCI while brain edema was not affected. Only interleukin (IL-1β gene expression was increased after CCI in the Tlr2/4−/− relative to WT mice. Inducible nitric oxide synthetase, TNF, IL-6, and COX-2 were similar in injured WT and Tlr2/4−/− mice, while the increase in high-mobility group box 1 was attenuated at 6 h. TLR2 and 4 are consequently shown to potentially promote secondary brain injury after experimental CCI via neuroinflammation and may therefore represent a novel therapeutic target for the treatment of TBI.

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

    DEFF Research Database (Denmark)

    Madsen, Kathrine Skak; Jernigan, Terry L; Vestergaard, Martin

    2018-01-01

    and limbic brain regions are the cingulum bundle and uncinate fasciculus. We previously found that healthy adults with higher neuroticism scores had decreased left relative to right fractional anisotropy (FA) of the cingulum. Both cingulum and uncinate fasciculus FA increases throughout childhood...... and into early adulthood. Since adolescence is associated with an increased incidence of anxiety and mood disorders, for which neuroticism is a known risk factor, the question arises whether the association between neuroticism and fronto-limbic white matter microstructure asymmetry is already present in children...

  4. Repetitive low-frequency stimulation reduces epileptiform synchronization in limbic neuronal networks.

    Science.gov (United States)

    D'Arcangelo, G; Panuccio, G; Tancredi, V; Avoli, M

    2005-01-01

    Deep-brain electrical or transcranial magnetic stimulation may represent a therapeutic tool for controlling seizures in patients presenting with epileptic disorders resistant to antiepileptic drugs. In keeping with this clinical evidence, we have reported that repetitive electrical stimuli delivered at approximately 1 Hz in mouse hippocampus-entorhinal cortex (EC) slices depress the EC ability to generate ictal activity induced by the application of 4-aminopyridine (4AP) or Mg(2+)-free medium (Barbarosie, M., Avoli, M., 1997. CA3-driven hippocampal-entorhinal loop controls rather than sustains in vitro limbic seizures. J. Neurosci. 17, 9308-9314.). Here, we confirmed a similar control mechanism in rat brain slices analyzed with field potential recordings during 4AP (50 microM) treatment. In addition, we used intrinsic optical signal (IOS) recordings to quantify the intensity and spatial characteristics of this inhibitory influence. IOSs reflect the changes in light transmittance throughout the entire extent of the slice, and are thus reliable markers of limbic network epileptiform synchronization. First, we found that in the presence of 4AP, the IOS increases, induced by a train of electrical stimuli (10 Hz for 1 s) or by recurrent, single-shock stimulation delivered at 0.05 Hz in the deep EC layers, are reduced in intensity and area size by low-frequency (1 Hz), repetitive stimulation of the subiculum; these effects were observed in all limbic areas contained in the slice. Second, by testing the effects induced by repetitive subicular stimulation at 0.2-10 Hz, we identified maximal efficacy when repetitive stimuli are delivered at 1 Hz. Finally, we discovered that similar, but slightly less pronounced, inhibitory effects occur when repetitive stimuli at 1 Hz are delivered in the EC, suggesting that the reduction of IOSs seen during repetitive stimulation is pathway dependent as well as activity dependent. Thus, the activation of limbic networks at low frequency

  5. Volumetric MRI of the limbic system: anatomic determinants

    Energy Technology Data Exchange (ETDEWEB)

    Bilir, E.; Craven, W.; Hugg, J.; Gilliam, F.; Martin, R.; Faught, E.; Kuzniecky, R. [UAB Epilepsy Center, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL (United States)

    1998-03-01

    The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. It is involved in complex functions including memory and emotion and in diseases such as temporal lobe epilepsy. Volume measurements of the amygdala and hippocampus have been used reliably to study patients with temporal lobe epilepsy but have not extended to other limbic structures. We performed volume measurements of hippocampus, amygdala, fornix and mamillary bodies in healthy individuals. Measurements of the amygdala, hippocampus, fornix and mamillary bodies revealed significant differences in volume between right and left sides (P < 0.001). The intraclass coefficient of variation for measurements was high for all structures except the mamillary bodies. Qualitative image assessment of the same structures revealed no asymmetries between the hemispheres. This technique can be applied to the study of disorders affecting the limbic system. (orig.) With 4 figs., 2 tabs., 23 refs.

  6. Volumetric MRI of the limbic system: anatomic determinants

    International Nuclear Information System (INIS)

    Bilir, E.; Craven, W.; Hugg, J.; Gilliam, F.; Martin, R.; Faught, E.; Kuzniecky, R.

    1998-01-01

    The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. It is involved in complex functions including memory and emotion and in diseases such as temporal lobe epilepsy. Volume measurements of the amygdala and hippocampus have been used reliably to study patients with temporal lobe epilepsy but have not extended to other limbic structures. We performed volume measurements of hippocampus, amygdala, fornix and mamillary bodies in healthy individuals. Measurements of the amygdala, hippocampus, fornix and mamillary bodies revealed significant differences in volume between right and left sides (P < 0.001). The intraclass coefficient of variation for measurements was high for all structures except the mamillary bodies. Qualitative image assessment of the same structures revealed no asymmetries between the hemispheres. This technique can be applied to the study of disorders affecting the limbic system. (orig.)

  7. Hypothermia in VGKC antibody-associated limbic encephalitis.

    Science.gov (United States)

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

    2008-02-01

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

  8. [Rasmussen encephalitis and non-herpetic acute limbic encephalitis].

    Science.gov (United States)

    Takahashi, Yukitoshi; Kubota, Yuko; Yamasaki, Etsuko; Matsuda, Kazumi

    2008-03-01

    Rasmussen syndrome (RS) and non-herpetic acute limbic encephalitis (NHALE) have pathophysiological background related with autoimmunity to glutamate receptors (GluRs) after infections. RS and NHALE were reviewed, depending mainly on our recent studies. RS is the prototype of autoimmune-mediated epilepsy. In patients with RS, several kinds of autoantibodies against neuronal molecules, for example, GluR3, GluRepsilon2 (NMDA-R2B), etc., are reported. These autoantibodies are not specific for RS. About autoantibodies against GluR3, significance and stimulating effects to GluR3 are controversial. Autoantibodies against GluRepsilon2 were detected in all patients within six months from epilepsy onset, and in some patients at chronic stage. These data suggest that autoantibodies against GluRepsilon2 may be involved in the pathological mechanisms in the early stage, but we could not confirm the effect of the autoantibodies from RS patients on excitatory postsynaptic NMDA current using patch clump methods. However, anti-double-stranded DNA antibodies in patients with SLE are reported to cross-react with n-terminal of GluRepsilon2, and cause neuronal apoptosis in rat hippocampus, ensuing memory impairment, and emotional behavior impairment in mice. Therefore, autoantibodies against GluRepsilon2 may contribute to the cognitive and behavioral changes in RS. Concerning about cellular immunity in RS, lymphocytes stimulating tests revealed peripheral lymphocytes sensitized by antigens containing GluRepsilon2. Cytotoxic T cells (CTLs) excreting Granzyme B were reported in resected brain tissue, and we confirmed the elevated levels of Granzyme B, not in sera, but in CSF. These data suggest that CTLs activated by infection invade into CNS, and recognize neural antigens, and excrete Granzyme B. The incidence of NHALE is 4.1/1 million/year in Japanese adults. Our study in 91 adult patients with NHALE revealed the following characteristics. Mean onset age was 35.2 +/- 16.9 years old

  9. Attenuated traumatic axonal injury and improved functional outcome after traumatic brain injury in mice lacking Sarm1.

    Science.gov (United States)

    Henninger, Nils; Bouley, James; Sikoglu, Elif M; An, Jiyan; Moore, Constance M; King, Jean A; Bowser, Robert; Freeman, Marc R; Brown, Robert H

    2016-04-01

    Axonal degeneration is a critical, early event in many acute and chronic neurological disorders. It has been consistently observed after traumatic brain injury, but whether axon degeneration is a driver of traumatic brain injury remains unclear. Molecular pathways underlying the pathology of traumatic brain injury have not been defined, and there is no efficacious treatment for traumatic brain injury. Here we show that mice lacking the mouse Toll receptor adaptor Sarm1 (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) gene, a key mediator of Wallerian degeneration, demonstrate multiple improved traumatic brain injury-associated phenotypes after injury in a closed-head mild traumatic brain injury model. Sarm1(-/-) mice developed fewer β-amyloid precursor protein aggregates in axons of the corpus callosum after traumatic brain injury as compared to Sarm1(+/+) mice. Furthermore, mice lacking Sarm1 had reduced plasma concentrations of the phophorylated axonal neurofilament subunit H, indicating that axonal integrity is maintained after traumatic brain injury. Strikingly, whereas wild-type mice exibited a number of behavioural deficits after traumatic brain injury, we observed a strong, early preservation of neurological function in Sarm1(-/-) animals. Finally, using in vivo proton magnetic resonance spectroscopy we found tissue signatures consistent with substantially preserved neuronal energy metabolism in Sarm1(-/-) mice compared to controls immediately following traumatic brain injury. Our results indicate that the SARM1-mediated prodegenerative pathway promotes pathogenesis in traumatic brain injury and suggest that anti-SARM1 therapeutics are a viable approach for preserving neurological function after traumatic brain injury. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. High Grade Glioma Mimicking Voltage Gated Potassium Channel Complex Associated Antibody Limbic Encephalitis

    Directory of Open Access Journals (Sweden)

    Dilan Athauda

    2014-01-01

    Full Text Available Though raised titres of voltage gated potassium channel (VGKC complex antibodies have been occasionally associated with extracranial tumours, mainly presenting as Morvan's Syndrome or neuromyotonia, they have not yet been reported to be associated with an intracranial malignancy. This is especially important as misdiagnosis of these conditions and delay of the appropriate treatment can have important prognostic implications. We describe a patient with a high grade glioma presenting with clinical, radiological, and serological features consistent with the diagnosis of VGKC antibody associated limbic encephalitis (LE. This is the first association between a primary brain tumour and high titre of VGKC complex antibodies. Clinicoradiological progression despite effective immunosuppressive treatment should prompt clinicians to look for alternative diagnoses. Further studies to elucidate a possible association between VGKC complex and other surface antigen antibodies with primary brain tumours should be carried out.

  11. High grade glioma mimicking voltage gated potassium channel complex associated antibody limbic encephalitis.

    Science.gov (United States)

    Athauda, Dilan; Delamont, R S; Pablo-Fernandez, E De

    2014-01-01

    Though raised titres of voltage gated potassium channel (VGKC) complex antibodies have been occasionally associated with extracranial tumours, mainly presenting as Morvan's Syndrome or neuromyotonia, they have not yet been reported to be associated with an intracranial malignancy. This is especially important as misdiagnosis of these conditions and delay of the appropriate treatment can have important prognostic implications. We describe a patient with a high grade glioma presenting with clinical, radiological, and serological features consistent with the diagnosis of VGKC antibody associated limbic encephalitis (LE). This is the first association between a primary brain tumour and high titre of VGKC complex antibodies. Clinicoradiological progression despite effective immunosuppressive treatment should prompt clinicians to look for alternative diagnoses. Further studies to elucidate a possible association between VGKC complex and other surface antigen antibodies with primary brain tumours should be carried out.

  12. Attenuating brain edema, hippocampal oxidative stress, and cognitive dysfunction in rats using hyperbaric oxygen preconditioning during simulated high-altitude exposure.

    Science.gov (United States)

    Lin, Hung; Chang, Ching-Ping; Lin, Hung-Jung; Lin, Mao-Tsun; Tsai, Cheng-Chia

    2012-05-01

    We assessed whether hyperbaric oxygen preconditioning (HBO2P) in rats induced heat shock protein (HSP)-70 and whether HSP-70 antibody (Ab) preconditioning attenuates high altitude exposure (HAE)-induced brain edema, hippocampal oxidative stress, and cognitive dysfunction. Rats were randomly divided into five groups: the non-HBO2P + non-HAE group, the HBO2P + non-HAE group, the non-HBO2P + HAE group, the HBO2P + HAE group, and the HBO2P + HSP-70 Abs + HAE group. The HBO2P groups were given 100% O2 at 2.0 absolute atmospheres for 1 hour per day for 5 consecutive days. The HAE groups were exposed to simulated HAE (9.7% O2 at 0.47 absolute atmospheres of 6,000 m) in a hypobaric chamber for 3 days. Polyclonal rabbit anti-mouse HSP-70-neutralizing Abs were intravenously injected 24 hours before the HAE experiments. Immediately after returning to normal atmosphere, the rats were given cognitive performance tests, overdosed with a general anesthetic, and then their brains were excised en bloc for water content measurements and biochemical evaluation and analysis. Non-HBO2P group rats displayed cognitive deficits, brain edema, and hippocampal oxidative stress (evidenced by increased toxic oxidizing radicals [e.g., nitric oxide metabolites and hydroxyl radicals], increased pro-oxidant enzymes [e.g., malondialdehyde and oxidized glutathione] but decreased antioxidant enzymes [e.g., reduced glutathione, glutathione peroxide, glutathione reductase, and superoxide dismutase]) in HAE. HBO2P induced HSP-70 overexpression in the hippocampus and significantly attenuated HAE-induced brain edema, cognitive deficits, and hippocampal oxidative stress. The beneficial effects of HBO2P were significantly reduced by HSP-70 Ab preconditioning. Our results suggest that high-altitude cerebral edema, cognitive deficit, and hippocampal oxidative stress can be prevented by HSP-70-mediated HBO2P in rats.

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

    Science.gov (United States)

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

    2014-12-01

    Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (∼ 45 mm Hg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (V(T)) was alternated every 90 s between high VT (0.96 ± 0.23 L) that provided respiratory comfort (12 ± 6% full scale) and low V(T) (0.48 ± 0.08 L) which evoked air hunger (56 ± 11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak 40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Sex differences in effective fronto-limbic connectivity during negative emotion processing.

    Science.gov (United States)

    Lungu, Ovidiu; Potvin, Stéphane; Tikàsz, Andràs; Mendrek, Adrianna

    2015-12-01

    In view of the greater prevalence of depression and anxiety disorders in women than in men, functional magnetic resonance imaging (fMRI) studies have examined sex-differences in brain activations during emotion processing. Comparatively, sex-differences in brain connectivity received little attention, despite evidence for important fronto-limbic connections during emotion processing across sexes. Here, we investigated sex-differences in fronto-limbic connectivity during negative emotion processing. Forty-six healthy individuals (25 women, 21 men) viewed negative, positive and neutral images during an fMRI session. Effective connectivity between significantly activated regions was examined using Granger causality and psychophysical interaction analyses. Sex steroid hormones and feminine-masculine traits were also measured. Subjective ratings of negative emotional images were higher in women than in men. Across sexes, significant activations were observed in the dorso-medial prefrontal cortex (dmPFC) and the right amygdala. Granger connectivity from right amygdala was significantly greater than that from dmPFC during the 'high negative' condition, an effect driven by men. Magnitude of this effect correlated negatively with highly negative image ratings and feminine traits and positively with testosterone levels. These results highlight critical sex differences in brain connectivity during negative emotion processing and point to the fact that both biological (sex steroid hormones) and psychosocial (gender role and identity) variables contribute to them. As the dmPFC is involved in social cognition and action planning, and the amygdala-in threat detection, the connectivity results suggest that compared to women, men have a more evaluative, rather than purely affective, brain response during negative emotion processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Attenuation measures of the BrainLAB imaging couch and validation on the treatment planning system Eclipse; Medidas de atenuacao da mesa BrainLAB imaging couch e validacao no sistema de planejamento Eclipse

    Energy Technology Data Exchange (ETDEWEB)

    Serante, Alexandre R., E-mail: alexandre.serante@gmail.com [Clinica de Radioterapia Inga, Nitero, RJ (Brazil); Goncalves, Joao G. [Instituto Oncologico, Juiz de Fora, MG (Brazil); Neves-Junior, Wellington F.P.; Leite, Joao Paulo S.; Haddad, Cecilia M.K. [Hospital Sirio-Libanes, Sao Paulo, SP (Brazil). Servico de Radioterapia. Sociedade Beneficente de Senhoras

    2015-12-15

    In this work, attenuation measurements were performed for the beams of energy 6 and 15MV for the couch table BrainLAB Imaging Couch, consisting of carbon fiber. The measurements were performed in the Linac Novalis-Tx (Varian) for 5 x 5 and 10 x 10 cm² field sizes, varying gantry positions. The measured data were compared with the values calculated with the treatment planning system Eclipse, calculated with the algorithm AAA, in order to validate the model of the couch included in your library. The highest attenuation for the field size of 10 x 10 cm² was 7,5% and 4,8% for the beams 6 and 15 MV, respectively. With the field size of 5 x 5 cm² the highest attenuation value was 8,1% and 5,3%, for the beams 6 and 15 MV, respectively. Both measured at gantry position 120 deg C. From the attenuation data measured with an ionization chamber, it was possible to modify the model of the couch in Eclipse to obtain the smallest difference between measured and predicted values by the TPS. (author)

  16. Toward implementing an MRI-based PET attenuation-correction method for neurologic studies on the MR-PET brain prototype.

    Science.gov (United States)

    Catana, Ciprian; van der Kouwe, Andre; Benner, Thomas; Michel, Christian J; Hamm, Michael; Fenchel, Matthias; Fischl, Bruce; Rosen, Bruce; Schmand, Matthias; Sorensen, A Gregory

    2010-09-01

    Several factors have to be considered for implementing an accurate attenuation-correction (AC) method in a combined MR-PET scanner. In this work, some of these challenges were investigated, and an AC method based entirely on the MRI data obtained with a single dedicated sequence was developed and used for neurologic studies performed with the MR-PET human brain scanner prototype. The focus was on the problem of bone-air segmentation, selection of the linear attenuation coefficient for bone, and positioning of the radiofrequency coil. The impact of these factors on PET data quantification was studied in simulations and experimental measurements performed on the combined MR-PET scanner. A novel dual-echo ultrashort echo time (DUTE) MRI sequence was proposed for head imaging. Simultaneous MR-PET data were acquired, and the PET images reconstructed using the proposed DUTE MRI-based AC method were compared with the PET images that had been reconstructed using a CT-based AC method. Our data suggest that incorrectly accounting for the bone tissue attenuation can lead to large underestimations (>20%) of the radiotracer concentration in the cortex. Assigning a linear attenuation coefficient of 0.143 or 0.151 cm(-1) to bone tissue appears to give the best trade-off between bias and variability in the resulting images. Not identifying the internal air cavities introduces large overestimations (>20%) in adjacent structures. On the basis of these results, the segmented CT AC method was established as the silver standard for the segmented MRI-based AC method. For an integrated MR-PET scanner, in particular, ignoring the radiofrequency coil attenuation can cause large underestimations (i.e.,

  17. Quantitative Evaluation of 2 Scatter-Correction Techniques for 18F-FDG Brain PET/MRI in Regard to MR-Based Attenuation Correction.

    Science.gov (United States)

    Teuho, Jarmo; Saunavaara, Virva; Tolvanen, Tuula; Tuokkola, Terhi; Karlsson, Antti; Tuisku, Jouni; Teräs, Mika

    2017-10-01

    In PET, corrections for photon scatter and attenuation are essential for visual and quantitative consistency. MR attenuation correction (MRAC) is generally conducted by image segmentation and assignment of discrete attenuation coefficients, which offer limited accuracy compared with CT attenuation correction. Potential inaccuracies in MRAC may affect scatter correction, because the attenuation image (μ-map) is used in single scatter simulation (SSS) to calculate the scatter estimate. We assessed the impact of MRAC to scatter correction using 2 scatter-correction techniques and 3 μ-maps for MRAC. Methods: The tail-fitted SSS (TF-SSS) and a Monte Carlo-based single scatter simulation (MC-SSS) algorithm implementations on the Philips Ingenuity TF PET/MR were used with 1 CT-based and 2 MR-based μ-maps. Data from 7 subjects were used in the clinical evaluation, and a phantom study using an anatomic brain phantom was conducted. Scatter-correction sinograms were evaluated for each scatter correction method and μ-map. Absolute image quantification was investigated with the phantom data. Quantitative assessment of PET images was performed by volume-of-interest and ratio image analysis. Results: MRAC did not result in large differences in scatter algorithm performance, especially with TF-SSS. Scatter sinograms and scatter fractions did not reveal large differences regardless of the μ-map used. TF-SSS showed slightly higher absolute quantification. The differences in volume-of-interest analysis between TF-SSS and MC-SSS were 3% at maximum in the phantom and 4% in the patient study. Both algorithms showed excellent correlation with each other with no visual differences between PET images. MC-SSS showed a slight dependency on the μ-map used, with a difference of 2% on average and 4% at maximum when a μ-map without bone was used. Conclusion: The effect of different MR-based μ-maps on the performance of scatter correction was minimal in non-time-of-flight 18 F-FDG PET

  18. Fresh-frozen plasma resuscitation after traumatic brain injury and shock attenuates extracellular nucleosome levels and deoxyribonuclease 1 depletion

    DEFF Research Database (Denmark)

    Sillesen, Martin; Jin, Guang; Oklu, Rahmi

    2013-01-01

    Traumatic brain injury and shock are among the leading causes of trauma-related mortality. We have previously shown that fresh-frozen plasma (FFP) resuscitation reduces the size of brain lesion and associated swelling compared with crystalloids. We hypothesized that this effect would be associated...

  19. Quantitative Evaluation of Atlas-based Attenuation Correction for Brain PET in an Integrated Time-of-Flight PET/MR Imaging System.

    Science.gov (United States)

    Yang, Jaewon; Jian, Yiqiang; Jenkins, Nathaniel; Behr, Spencer C; Hope, Thomas A; Larson, Peder E Z; Vigneron, Daniel; Seo, Youngho

    2017-07-01

    Purpose To assess the patient-dependent accuracy of atlas-based attenuation correction (ATAC) for brain positron emission tomography (PET) in an integrated time-of-flight (TOF) PET/magnetic resonance (MR) imaging system. Materials and Methods Thirty recruited patients provided informed consent in this institutional review board-approved study. All patients underwent whole-body fluorodeoxyglucose PET/computed tomography (CT) followed by TOF PET/MR imaging. With use of TOF PET data, PET images were reconstructed with four different attenuation correction (AC) methods: PET with patient CT-based AC (CTAC), PET with ATAC (air and bone from an atlas), PET with ATAC patientBone (air and tissue from the atlas with patient bone), and PET with ATAC boneless (air and tissue from the atlas without bone). For quantitative evaluation, PET mean activity concentration values were measured in 14 1-mL volumes of interest (VOIs) distributed throughout the brain and statistical significance was tested with a paired t test. Results The mean overall difference (±standard deviation) of PET with ATAC compared with PET with CTAC was -0.69 kBq/mL ± 0.60 (-4.0% ± 3.2) (P PET with ATAC boneless (-9.4% ± 3.7) was significantly worse than that of PET with ATAC (-4.0% ± 3.2) (P PET with ATAC patientBone (-1.5% ± 1.5) improved over that of PET with ATAC (-4.0% ± 3.2) (P PET/MR imaging achieves similar quantification accuracy to that from CTAC by means of atlas-based bone compensation. However, patient-specific anatomic differences from the atlas causes bone attenuation differences and misclassified sinuses, which result in patient-dependent performance variation of ATAC. © RSNA, 2017 Online supplemental material is available for this article.

  20. Dorsal root ganglion stimulation attenuates the BOLD signal response to noxious sensory input in specific brain regions: Insights into a possible mechanism for analgesia.

    Science.gov (United States)

    Pawela, Christopher P; Kramer, Jeffery M; Hogan, Quinn H

    2017-02-15

    Targeted dorsal root ganglion (DRG) electrical stimulation (i.e. ganglionic field stimulation - GFS) is an emerging therapeutic approach to alleviate chronic pain. Here we describe blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to noxious hind-limb stimulation in a rat model that replicates clinical GFS using an electrode implanted adjacent to the DRG. Acute noxious sensory stimulation in the absence of GFS caused robust BOLD fMRI response in brain regions previously associated with sensory and pain-related response, such as primary/secondary somatosensory cortex, retrosplenial granular cortex, thalamus, caudate putamen, nucleus accumbens, globus pallidus, and amygdala. These regions differentially demonstrated either positive or negative correlation to the acute noxious stimulation paradigm, in agreement with previous rat fMRI studies. Therapeutic-level GFS significantly attenuated the global BOLD response to noxious stimulation in these regions. This BOLD signal attenuation persisted for 20minutes after the GFS was discontinued. Control experiments in sham-operated animals showed that the attenuation was not due to the effect of repetitive noxious stimulation. Additional control experiments also revealed minimal BOLD fMRI response to GFS at therapeutic intensity when presented in a standard block-design paradigm. High intensity GFS produced a BOLD signal map similar to acute noxious stimulation when presented in a block-design. These findings are the first to identify the specific brain region responses to neuromodulation at the DRG level and suggest possible mechanisms for GFS-induced treatment of chronic pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Glioblastoma in the limbic system presenting as sustained central hypopnea

    Directory of Open Access Journals (Sweden)

    Ryota Mashiko

    2017-03-01

    Full Text Available A 71-year-old woman was transferred to our hospital after experiencing an epigastric sensation followed by unconsciousness. On arrival, the patient showed impaired consciousness without convulsive movement, cyanosis and shallow breathing, arterial O2 desaturation, and increased PCO2. Artificial respiration improved CO2 accumulation and consciousness, but interruption of artificial respiration returned the patient to her former state. Computed tomography of the head showed a mass around the left corpus callosum. The patient's hypopnea followed by unconsciousness suggested sustained nonconvulsive epilepsy manifesting in central hypopnea and subsequent unconsciousness due to CO2 narcosis. Intravenous (IV anticonvulsants promptly improved the respiratory condition, and the patient started to regain consciousness. Magnetic resonance imaging revealed a lesion involving the bilateral limbic systems. To our knowledge, limbic seizure manifesting with hypopnea causing unconsciousness due to CO2 narcosis has not previously been reported, despite evidence of a strong relationship between the limbic and respiratory systems. The current case suggests that sustained limbic seizure can manifest as hypopnea. Since emergency EEG can be difficult to perform, IV anticonvulsant treatment is an appropriate diagnostic therapy.

  2. Cortical and limbic excitability in rats with absence epilepsy

    NARCIS (Netherlands)

    Tolmacheva, E.A.; Luijtelaar, E.L.J.M. van; Chepurnov, S.A.; Kaminskij, Y.; Mares, P.

    2004-01-01

    The classical cortico-reticular theory on absence epilepsy suggests that a hyperexcitable cortex is a precondition for the occurrence of absence seizures. In the present experiment seizure thresholds and characteristics of cortical and limbic epileptic afterdischarges (AD) were determined in a

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

    Science.gov (United States)

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

    2010-09-01

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

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

    Science.gov (United States)

    Frühholz, Sascha; Trost, Wiebke; Grandjean, Didier

    2014-12-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marion Alcantara

    2013-05-01

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

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

    Science.gov (United States)

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

    2016-01-20

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Science.gov (United States)

    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.

  11. A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model

    Directory of Open Access Journals (Sweden)

    McNamara Laurie K

    2007-09-01

    Full Text Available Abstract Background An accumulating body of evidence is consistent with the hypothesis that excessive or prolonged increases in proinflammatory cytokine production by activated glia is a contributor to the progression of pathophysiology that is causally linked to synaptic dysfunction and hippocampal behavior deficits in neurodegenerative diseases such as Alzheimer's disease (AD. This raises the opportunity for the development of new classes of potentially disease-modifying therapeutics. A logical candidate CNS target is p38α MAPK, a well-established drug discovery molecular target for altering proinflammatory cytokine cascades in peripheral tissue disorders. Activated p38 MAPK is seen in human AD brain tissue and in AD-relevant animal models, and cell culture studies strongly implicate p38 MAPK in the increased production of proinflammatory cytokines by glia activated with human amyloid-beta (Aβ and other disease-relevant stressors. However, the vast majority of small molecule drugs do not have sufficient penetrance of the blood-brain barrier to allow their use as in vivo research tools or as therapeutics for neurodegenerative disorders. The goal of this study was to test the hypothesis that brain p38α MAPK is a potential in vivo target for orally bioavailable, small molecules capable of suppressing excessive cytokine production by activated glia back towards homeostasis, allowing an improvement in neurologic outcomes. Methods A novel synthetic small molecule based on a molecular scaffold used previously was designed, synthesized, and subjected to analyses to demonstrate its potential in vivo bioavailability, metabolic stability, safety and brain uptake. Testing for in vivo efficacy used an AD-relevant mouse model. Results A novel, CNS-penetrant, non-toxic, orally bioavailable, small molecule inhibitor of p38α MAPK (MW01-2-069A-SRM was developed. Oral administration of the compound at a low dose (2.5 mg/kg resulted in attenuation of

  12. An SPM8-based approach for attenuation correction combining segmentation and nonrigid template formation: application to simultaneous PET/MR brain imaging.

    Science.gov (United States)

    Izquierdo-Garcia, David; Hansen, Adam E; Förster, Stefan; Benoit, Didier; Schachoff, Sylvia; Fürst, Sebastian; Chen, Kevin T; Chonde, Daniel B; Catana, Ciprian

    2014-11-01

    We present an approach for head MR-based attenuation correction (AC) based on the Statistical Parametric Mapping 8 (SPM8) software, which combines segmentation- and atlas-based features to provide a robust technique to generate attenuation maps (μ maps) from MR data in integrated PET/MR scanners. Coregistered anatomic MR and CT images of 15 glioblastoma subjects were used to generate the templates. The MR images from these subjects were first segmented into 6 tissue classes (gray matter, white matter, cerebrospinal fluid, bone, soft tissue, and air), which were then nonrigidly coregistered using a diffeomorphic approach. A similar procedure was used to coregister the anatomic MR data for a new subject to the template. Finally, the CT-like images obtained by applying the inverse transformations were converted to linear attenuation coefficients to be used for AC of PET data. The method was validated on 16 new subjects with brain tumors (n = 12) or mild cognitive impairment (n = 4) who underwent CT and PET/MR scans. The μ maps and corresponding reconstructed PET images were compared with those obtained using the gold standard CT-based approach and the Dixon-based method available on the Biograph mMR scanner. Relative change (RC) images were generated in each case, and voxel- and region-of-interest-based analyses were performed. The leave-one-out cross-validation analysis of the data from the 15 atlas-generation subjects showed small errors in brain linear attenuation coefficients (RC, 1.38% ± 4.52%) compared with the gold standard. Similar results (RC, 1.86% ± 4.06%) were obtained from the analysis of the atlas-validation datasets. The voxel- and region-of-interest-based analysis of the corresponding reconstructed PET images revealed quantification errors of 3.87% ± 5.0% and 2.74% ± 2.28%, respectively. The Dixon-based method performed substantially worse (the mean RC values were 13.0% ± 10.25% and 9.38% ± 4.97%, respectively). Areas closer to the skull showed

  13. RESOLUTE PET/MRI Attenuation Correction for O-(2-F-fluoroethyl)-L-tyrosine (FET) in Brain Tumor Patients with Metal Implants

    DEFF Research Database (Denmark)

    Ladefoged, Claes N; Andersen, Flemming L; Kjær, Andreas

    2017-01-01

    of agreement for TMAX/B was for RESOLUTE (-3%; 4%), Dixon (-9%; 16%), and UTE (-7%; 10%). The absolute error when measuring BTV was 0.7 ± 1.9 mL (N.S) with RESOLUTE, 5.3 ± 10 mL using Dixon, and 1.7 ± 3.7 mL using UTE. RESOLUTE performed best in the identification of the location of peak activity and in brain...... to be quantitatively correct in order to be used clinically, which require accurate attenuation correction (AC) in PET/MRI. The aim of this study was to evaluate the use of the subject-specific MR-derived AC method RESOLUTE in post-operative brain tumor patients.Methods:We analyzed 51 post-operative brain tumor...... patients (68 examinations, 200 MBq [18F]-FET) investigated in a PET/MRI scanner. MR-AC maps were acquired using: (1) the Dixon water fat separation sequence, (2) the ultra short echo time (UTE) sequences, (3) calculated using our new RESOLUTE methodology, and (4) a same day low-dose CT used as reference...

  14. Pretreatment with Shuanghe-Tang Extract Attenuates Postischemic Brain Injury and Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui Bogam

    Directory of Open Access Journals (Sweden)

    Min Jae Kim

    2018-01-01

    Full Text Available Aim. Although stroke is among the leading causes of death and long-term disability, there are few effective treatments for limiting the severity of neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke symptoms in a mouse model of cerebral ischemia. Methods. Focal cerebral ischemia was induced via photothrombosis. Infarct volume, brain edema, and neurological deficits were evaluated. Immunofluorescence staining for tight junction proteins and aquaporin 4 (AQP4 was performed following ischemic injury. Results. Based on our initial findings, we examined the effects of two prescriptions in which the candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct volume, decreased blood-brain barrier (BBB breakdown, attenuated edema, and improved neurological and motor functions in a dose-dependent manner (30, 100, and 300 mg/kg, while no such effects were observed in mice pretreated with Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in ipsilateral occludin and zonula occludens 1 (ZO-1 expression in Shuanghe-tang-pretreated mice, as well as increased AQP4 immunofluorescence. Conclusions. These results indicate that Shuanghe-tang may protect against brain injury and promote recovery of neurological function following ischemia.

  15. The behaviour and brain function of the Cichlid fish ...

    African Journals Online (AJOL)

    ... the teleost forebrain houses a primitive limbic system the main functions of which would be general arousal and the selection of appropriate responses to the incoming external and endogenous (motivational) stimuli. Keywords: Brain Function, Teleost, telencephalon, Cichlid fish behaviour, limbic system, hippocampus ...

  16. Increased expression of vascular endothelial growth factor attenuates contusion necrosis without influencing contusion edema after traumatic brain injury in rats.

    Science.gov (United States)

    Tado, Masahiro; Mori, Tatsuro; Fukushima, Masamichi; Oshima, Hideki; Maeda, Takeshi; Yoshino, Atsuo; Aizawa, Shin; Katayama, Yoichi

    2014-04-01

    To clarify the role of vascular endothelial growth factor (VEGF) in the formation of contusion edema and necrosis after traumatic brain injury, we examined the time course of changes in the VEGF expression (enzyme-linked immunosorbent assay), cerebrovascular permeability (extravasation of Evans blue), and water content (dry-wet weight method) of the contused brain tissue in a cortical impact injury model using rats. In addition, we tested the effects of administration of bevacizumab (VEGF monoclonal antibody) on changes in the cerebrovascular permeability and water content of the contused brain tissue, as well as the neurological deficits (rota rod test) and volume of contusion necrosis. Increased VEGF expression was maximal at 72 h after injury (pnecrosis at 21 days (pnecrosis. This is probably because of an increased angiogenesis and improved microcirculation in the areas surrounding the core of contusion.

  17. Attenuation of prostaglandin E2 elimination across the mouse blood-brain barrier in lipopolysaccharide-induced inflammation and additive inhibitory effect of cefmetazole

    Directory of Open Access Journals (Sweden)

    Akanuma Shin-ichi

    2011-10-01

    Full Text Available Abstract Background Peripheral administration of lipopolysaccharide (LPS induces inflammation and increases cerebral prostaglandin E2 (PGE2 concentration. PGE2 is eliminated from brain across the blood-brain barrier (BBB in mice, and this process is inhibited by intracerebral or intravenous pre-administration of anti-inflammatory drugs and antibiotics such as cefmetazole and cefazolin that inhibit multidrug resistance-associated protein 4 (Mrp4/Abcc4-mediated PGE2 transport. The purpose of this study was to examine the effect of LPS-induced inflammation on PGE2 elimination from brain, and whether antibiotics further inhibit PGE2 elimination in LPS-treated mice. Methods [3H]PGE2 elimination across the BBB of intraperitoneally LPS-treated mice was assessed by the brain efflux index (BEI method. Transporter protein amounts in brain capillaries were quantified by liquid chromatography-tandem mass spectrometry. Results The apparent elimination rate of [3H]PGE2 from brain was lower by 87%, in LPS-treated mice compared with saline-treated mice. The Mrp4 protein amount was unchanged in brain capillaries of LPS-treated mice compared with saline-treated mice, while the protein amounts of organic anion transporter 3 (Oat3/Slc22a8 and organic anion transporting polypeptide 1a4 (Oatp1a4/Slco1a4 were decreased by 26% and 39%, respectively. Either intracerebral or intravenous pre-administration of cefmetazole further inhibited PGE2 elimination in LPS-treated mice. However, intracerebral or intravenous pre-administration of cefazolin had little effect on PGE2 elimination in LPS-treated mice, or in LPS-untreated mice given Oat3 and Oatp1a4 inhibitors. These results indicate that peripheral administration of cefmetazole inhibits PGE2 elimination across the BBB in LPS-treated mice. Conclusion PGE2 elimination across the BBB is attenuated in an LPS-induced mouse model of inflammation. Peripheral administration of cefmetazole further inhibits PGE2 elimination in LPS

  18. Estrogen Receptor β Agonist Attenuates Endoplasmic Reticulum Stress-Induced Changes in Social Behavior and Brain Connectivity in Mice.

    Science.gov (United States)

    Crider, Amanda; Nelson, Tyler; Davis, Talisha; Fagan, Kiley; Vaibhav, Kumar; Luo, Matthew; Kamalasanan, Sunay; Terry, Alvin V; Pillai, Anilkumar

    2018-02-12

    Impaired social interaction is a key feature of several major psychiatric disorders including depression, autism, and schizophrenia. While, anatomically, the prefrontal cortex (PFC) is known as a key regulator of social behavior, little is known about the cellular mechanisms that underlie impairments of social interaction. One etiological mechanism implicated in the pathophysiology of the aforementioned psychiatric disorders is cellular stress and consequent adaptive responses in the endoplasmic reticulum (ER) that can result from a variety of environmental and physical factors. The ER is an organelle that serves essential roles in protein modification, folding, and maturation of proteins; however, the specific role of ER stress in altered social behavior is unknown. In this study, treatment with tunicamycin, an ER stress inducer, enhanced the phosphorylation level of inositol-requiring ER-to-nucleus signal kinase 1 (IRE1) and increased X-box-binding protein 1 (XBP1) mRNA splicing activity in the mouse PFC, whereas inhibition of IRE1/XBP1 pathway in PFC by a viral particle approach attenuated social behavioral deficits caused by tunicamycin treatment. Reduced estrogen receptor beta (ERβ) protein levels were found in the PFC of male mice following tunicamycin treatment. Pretreatment with an ERβ specific agonist, ERB-041 significantly attenuated tunicamycin-induced deficits in social behavior, and activation of IRE1/XBP1 pathway in mouse PFC. Moreover, ERB-041 inhibited tunicamycin-induced increases in functional connectivity between PFC and hippocampus in male mice. Together, these results show that ERβ agonist attenuates ER stress-induced deficits in social behavior through the IRE-1/XBP1 pathway.

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

    Science.gov (United States)

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

    2010-03-01

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

  20. Resuscitation with Pooled and Pathogen-Reduced Plasma Attenuates the Increase in Brain Water Content following Traumatic Brain Injury and Hemorrhagic Shock in Rats

    DEFF Research Database (Denmark)

    Genét, Gustav Folmer; Bentzer, Peter; Ostrowski, Sisse Rye

    2017-01-01

    brain injury, hemorrhage (20 mL/kg), and 90-min shock, 48 male Sprague-Dawley rats were randomized to resuscitation with OCTA, FFP, or NS (n = 16/group). Brain water content (wet/dry weight) and BBB permeability (transfer constant for51Cr-EDTA) were measured at 24 h. Plasma osmolality, oncotic pressure......, and biomarkers of systemic glycocalyx shedding (syndecan-1) and cell damage (histone-complexed DNA) were measured at 0 and 23 h. At 24 h, brain water content was 80.44 ± 0.39%, 80.82 ± 0.82%, and 81.15 ± 0.86% in the OCTA, FFP, and NS groups (lower in OCTA vs. NS; p = 0.026), with no difference in BBB...

  1. Limbic encephalitis presenting as a post-partum psychiatric condition.

    Science.gov (United States)

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

    2011-09-15

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

  2. Interleukin 6-Mediated Endothelial Barrier Disturbances Can Be Attenuated by Blockade of the IL6 Receptor Expressed in Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Blecharz-Lang, Kinga G; Wagner, Josephin; Fries, Alexa; Nieminen-Kelhä, Melina; Rösner, Jörg; Schneider, Ulf C; Vajkoczy, Peter

    2018-02-10

    Compromised blood-brain barrier (BBB) by dysregulation of cellular junctions is a hallmark of many cerebrovascular disorders due to the pro-inflammatory cytokines action. Interleukin 6 (IL6) is implicated in inflammatory processes and in secondary brain injury after subarachnoid hemorrhage (SAH) but its role in the maintenance of cerebral endothelium still requires a precise elucidation. Although IL6 has been shown to exert pro-inflammatory action on brain microvascular endothelial cells (ECs), the expression of one of the IL6 receptors, the IL6R is controversially discussed. In attempt to reach more clarity in this issue, we present here an evident baseline expression of the IL6R in BBB endothelium in vivo and in an in vitro model of the BBB, the cEND cell line. A significantly increased expression of IL6R and its ligand was observed in BBB capillaries 2 days after experimental SAH in mice. In vitro, we saw IL6 administration resulting in an intracellular and extracellular elevation of IL6 protein, which was accompanied by a reduced expression of tight and adherens junctions, claudin-5, occludin, and vascular-endothelial (VE-) cadherin. By functional assays, we could demonstrate IL6-incubated brain ECs to lose their endothelial integrity that can be attenuated by inhibiting the IL6R. Blockade of the IL6R by a neutralizing antibody has reconstituted the intercellular junction expression to the control level and caused a restoration of the transendothelial electrical resistance of the cEND cell monolayer. Our findings add depth to the current understanding of the involvement of the endothelial IL6R in the loss of EC integrity implicating potential therapy options.

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

    Directory of Open Access Journals (Sweden)

    Gian Luca Breschi

    2015-01-01

    Full Text Available 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.

  4. Chronic Stress and Limbic-Hypothalamopituitary-Adrenal Axis (LHPA Response in Female Reproductive system

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2009-12-01

    Full Text Available The hypothalamo-pituitary-adrenocortical (HPA axis is a critical adaptive system that maximizes survival potential in the face of physical or psychological challenge. The principal end products of the HPA axis, glucocorticoid hormones, act on multiple organ systems, including the brain, to maintain homeostatic balance. The brain is a target of stress, and the hippocampus is the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. These anatomical areas in brain are limbic system, and in particular the hippocampus, medial prefrontal cortex (mPFC and amigdal that have multiple control points in regulation of the hypothalamic–pituitary–adrenal (HPA axis. The studies show the prefrontal cortex (PFC plays an important role in the regulation of stress-induced hypothalamic–pituitary–adrenal (HPA activity and regulation of gonadal function in men and women is under the control of the HPA. This regulation is complex and sex steroids are important regulators of GnRH and gonadotropin release through classic feedback mechanisms in the hypothalamus and pituitary gland. Chronic stress can have a deleterious effect on the reproductive axis that, for females, is manifested in reduced pulsatile gonadotropin secretion and increased incidence of ovulatory abnormalities and infertility. The limbic–hypothalamic–pituitary–adrenal (LHPA axis suggests a functional role for gonadal steroids in the regulation of a female’s response to stress.

  5. Limbic encephalitis presenting as a post-partum psychiatric condition.

    OpenAIRE

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

    2011-01-01

    OBJECTIVE: We describe a woman who presented with a psychiatric disorder post-partum and subsequently developed seizures and cognitive dysfunction prompting further investigation. A diagnosis of limbic encephalitis (LE) was made and antibodies to voltage-gated potassium channel complex (VGKC) detected. These antibodies are found in many non-paraneoplastic patients with LE. Although antibody-mediated conditions tend to present or relapse post-partum, VGKC-LE in the post-partum period has not b...

  6. Prostaglandin E2 EP2 Receptor Deletion Attenuates Intracerebral Hemorrhage-Induced Brain Injury and Improves Functional Recovery

    Directory of Open Access Journals (Sweden)

    Jenna L. Leclerc

    2015-04-01

    Full Text Available Intracerebral hemorrhage (ICH is a devastating type of stroke characterized by bleeding into the brain parenchyma and secondary brain injury resulting from strong neuroinflammatory responses to blood components. Production of prostaglandin E2 (PGE2 is significantly upregulated following ICH and contributes to this inflammatory response in part through its E prostanoid receptor subtype 2 (EP2. Signaling through the EP2 receptor has been shown to affect outcomes of many acute and chronic neurological disorders; although, not yet explored in the context of ICH. Wildtype (WT and EP2 receptor knockout (EP2−/− mice were subjected to ICH, and various anatomical and functional outcomes were assessed by histology and neurobehavioral testing, respectively. When compared with age-matched WT controls, EP2−/− mice had 41.9 ± 4.7% smaller ICH-induced brain lesions and displayed significantly less ipsilateral hemispheric enlargement and incidence of intraventricular hemorrhage. Anatomical outcomes correlated with improved functional recovery as identified by neurological deficit scoring. Histological staining was performed to begin investigating the mechanisms involved in EP2-mediated neurotoxicity after ICH. EP2−/− mice exhibited 45.5 ± 5.8% and 41.4 ± 8.1% less blood and ferric iron accumulation, respectively. Furthermore, significantly less striatal and cortical microgliosis, striatal and cortical astrogliosis, blood–brain barrier breakdown, and peripheral neutrophil infiltration were seen in EP2−/− mice. This study is the first to suggest a deleterious role for the PGE2-EP2 signaling axis in modulating brain injury, inflammation, and functional recovery following ICH. Targeting the EP2 G protein-coupled receptor may represent a new therapeutic avenue for the treatment of hemorrhagic stroke.

  7. Clinical study on antibody-associated limbic encephalitis

    Directory of Open Access Journals (Sweden)

    WANG Jia-wei

    2013-01-01

    Full Text Available In recent years, the antibody-associated limbic encephalitis (LE has attracted attentions of more and more clinicians. The associated antibodies mainly act on neuronal cell surface antigens, including the N-methyl-D-aspartate (NMDA receptor, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA receptor, the γ-aminobutyric acid B (GABAB receptor, leucine-rich glioma-inactivated 1 (LGI1 and contactin-associated protein-like 2 (Caspr2 and so on. The clinical manifestation is primarily defined by the subacute onset of short-term memory loss, seizures, confusion and psychiatric symptoms suggesting the involvement of the limbic system. These severe and protracted disorders can affect children and young adults, occurring with or without tumor association. Routine detection of serum and cerebrospinal fluid (CSF and imaging tests show no specificity, but associated antibodies can be detected in serum and (or CSF. The patients respond well to tumor resection and immunotherapies, including corticosteroids, intravenous immunoglobulin (IVIg, plasma exchange or combination of them, but may relapse. This article aims to study the clinical features and treatment of antibody-associated limbic encephalitis and to improve the diagnosis and prognosis of these diseases.

  8. Limbic system, the main focus of dementia syndrome

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju

    1990-01-01

    Alzheimer disease and multi-infarct dementia are two entirely different diseases producing almost the same abnormalities as dementia syndrome. The statistical studies with MRI to locate the focus of dementia syndrome in the neocortex was an absolute failure. With MRI there is drastic atrophy and destruction of the amygdala and hippocampus suggesting the limbic system as the focus of dementia syndrome. Destruction of the limbic system in particular amygdala and hippocampus produced the functional obstruction brought about by the marked reduction in the glucose utilization with PET in the bilateral temporal, parietal and occipital association cortices. Although this type constitutes only about 1/5 of all dementia patients. It is considered the fundamental type of dementia syndrome. Aside from this, there is a type wherein simultaneous and symmetrical reductions in glucose utilization of the frontal association cortex and the motor association cortex in the anterior part of the neocortex. This is referred to as type II. It constitutes about 4/5 of all dementia patients which is far more than type I. Based on these results, it is thought that limbic system is the main focus of dementia syndrome. (author)

  9. Attenuation of alpha2A-adrenergic receptor expression in neonatal rat brain by RNA interference or antisense oligonucleotide reduced anxiety in adulthood.

    Science.gov (United States)

    Shishkina, G T; Kalinina, T S; Dygalo, N N

    2004-01-01

    Brain alpha2-adrenergic receptors (alpha2-ARs) have been implicated in the regulation of anxiety, which is associated with stress. Environmental treatments during neonatal development could modulate the level of brain alpha2-AR expression and alter anxiety in adults, suggesting possible involvement of these receptors in early-life programming of anxiety state. The present study was undertaken to determine whether the reduction of the expression of A subtype of these receptors most abundant in the neonatal brain affects anxiety-related behavior in adulthood. We attenuated the expression of alpha2A-ARs during neonatal life by two different sequence specific approaches, antisense technology and RNA interference. Treatment of rats with the antisense oligodeoxynucleotide or short interfering RNA (siRNA) against alpha2A-ARs on the days 2-4 of their life, produced a marked acute decrease in the levels of both alpha2A-AR mRNA and [3H]RX821002 binding sites in the brainstem into which drugs were injected. The decrease of alpha2A-AR expression in the neonatal brainstem influenced the development of this receptor system in the brain regions as evidenced by the increased number of [3H]RX821002 binding sites in the hypothalamus of adult animals with both neonatal alpha2A-AR knockdown treatments; also in the frontal cortex of antisense-treated, and in the hippocampus of siRNA-treated adult rats. These adult animals also demonstrated a decreased anxiety in the elevated plus-maze as evidenced by an increased number of the open arm entries, greater proportion of time spent in the open arms, and more than a two-fold increase in the number of exploratory head dips. The results provide the first evidence that the reduction in the brain expression of a gene encoding for alpha2A-AR during neonatal life led to the long-term neurochemical and behavioral alterations. The data suggests that alterations in the expression of the receptor-specific gene during critical periods of brain

  10. An SPM8-based Approach for Attenuation Correction Combining Segmentation and Non-rigid Template Formation: Application to Simultaneous PET/MR Brain Imaging

    Science.gov (United States)

    Izquierdo-Garcia, David; Hansen, Adam E.; Förster, Stefan; Benoit, Didier; Schachoff, Sylvia; Fürst, Sebastian; Chen, Kevin T.; Chonde, Daniel B.; Catana, Ciprian

    2014-01-01

    We present an approach for head MR-based attenuation correction (MR-AC) based on the Statistical Parametric Mapping (SPM8) software that combines segmentation- and atlas-based features to provide a robust technique to generate attenuation maps (µ-maps) from MR data in integrated PET/MR scanners. Methods Coregistered anatomical MR and CT images acquired in 15 glioblastoma subjects were used to generate the templates. The MR images from these subjects were first segmented into 6 tissue classes (gray and white matter, cerebro-spinal fluid, bone and soft tissue, and air), which were then non-rigidly coregistered using a diffeomorphic approach. A similar procedure was used to coregister the anatomical MR data for a new subject to the template. Finally, the CT-like images obtained by applying the inverse transformations were converted to linear attenuation coefficients (LACs) to be used for AC of PET data. The method was validated on sixteen new subjects with brain tumors (N=12) or mild cognitive impairment (N=4) who underwent CT and PET/MR scans. The µ-maps and corresponding reconstructed PET images were compared to those obtained using the gold standard CT-based approach and the Dixon-based method available on the Siemens Biograph mMR scanner. Relative change (RC) images were generated in each case and voxel- and region of interest (ROI)-based analyses were performed. Results The leave-one-out cross-validation analysis of the data from the 15 atlas-generation subjects showed small errors in brain LACs (RC=1.38%±4.52%) compared to the gold standard. Similar results (RC=1.86±4.06%) were obtained from the analysis of the atlas-validation datasets. The voxel- and ROI-based analysis of the corresponding reconstructed PET images revealed quantification errors of 3.87±5.0% and 2.74±2.28%, respectively. The Dixon-based method performed substantially worse (the mean RC values were 13.0±10.25% and 9.38±4.97%, respectively). Areas closer to skull showed the largest

  11. Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome?

    Science.gov (United States)

    Anthony, Karen; Reed, Laurence J; Dunn, Joel T; Bingham, Emma; Hopkins, David; Marsden, Paul K; Amiel, Stephanie A

    2006-11-01

    The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [(18)F]fluorodeoxyglucose positron emission tomography, in seven insulin-sensitive (homeostasis model assessment of insulin resistance [HOMA-IR] = 1.3) and seven insulin-resistant (HOMA-IR = 6.3) men, during suppression of endogenous insulin by somatostatin, with and without an insulin infusion that elevated insulin to 24.6 +/- 5.2 and 23.2 +/- 5.8 mU/l (P = 0.76), concentrations similar to fasting levels of the resistant subjects and approximately threefold above those of the insulin-sensitive subjects. Insulin-evoked change in global cerebral metabolic rate for glucose was reduced in insulin resistance (+7 vs. +17.4%, P = 0.033). Insulin was associated with increased metabolism in ventral striatum and prefrontal cortex and with decreased metabolism in right amygdala/hippocampus and cerebellar vermis (P reward. Diminishing the link be-tween control of food intake and energy balance may contribute to development of obesity in insulin resistance.

  12. Focal attenuation of specific electroencephalographic power over the right parahippocampal region during transcerebral copper screening in living subjects and hemispheric asymmetric voltages in fixed brain tissue.

    Science.gov (United States)

    Rouleau, Nicolas; Lehman, Brendan; Persinger, Michael A

    2016-08-01

    Covering the heads of human volunteers with a toque lined with copper mesh compared to no mesh resulted in significant diminishments in quantitative electroencephalographic power within theta and beta-gamma bands over the right caudal hemisphere. The effect was most evident in women compared to men. The significant attenuation of power was verified by LORETA (low resolution electromagnetic tomography) within the parahippocampal region of the right hemisphere. Direct measurements of frequency-dependent voltages of coronal section preserved in ethanol-formalin-acetic acid from our human brain collection revealed consistently elevated power (0.2μV(2)Hz(-1)) in right hemispheric structures compared to left. The discrepancy was most pronounced in the grey (cortical) matter of the right parahippocampal region. Probing the superficial convexities of the cerebrum in an unsectioned human brain demonstrated rostrocaudal differences in hemispheric spectral power density asymmetries, particularly over caudal and parahippocampal regions, which were altered as a function of the chemical and spatial contexts imposed upon the tissue. These results indicate that the heterogeneous response of the human cerebrum to covering of the head by a thin conductor could reflect an intrinsic structure and unique electrical property of the (entorhinal) cortices of the right caudal hemisphere that persists in fixed tissue. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Purple Sweet Potato Color Ameliorates Cognition Deficits and Attenuates Oxidative Damage and Inflammation in Aging Mouse Brain Induced by D-Galactose

    Directory of Open Access Journals (Sweden)

    Qun Shan

    2009-01-01

    Full Text Available Purple sweet potato color (PSPC, a naturally occurring anthocyanin, has a powerful antioxidant activity in vitro and in vivo. This study explores whether PSPC has the neuroprotective effect on the aging mouse brain induced by D-galactose (D-gal. The mice administrated with PSPC (100 mg/kg.day, 4 weeks, from 9th week via oral gavage showed significantly improved behavior performance in the open field and passive avoidance test compared with D-gal-treated mice (500 mg/kg.day, 8 weeks. We further investigate the mechanism involved in neuroprotective effects of PSPC on mouse brain. Interestingly, we found, PSPC decreased the expression level of glial fibrillary acidic protein (GFAP, inducible nitric oxide synthase (iNOS, and cyclooxygenase-2 (COX-2, inhibited nuclear translocation of nuclear factor-kappaB (NF-κB, increased the activity of copper/zinc superoxide dismutase (Cu/Zn-SOD and catalase (CAT, and reduced the content of malondialdehyde (MDA, respectively. Our data suggested that PSPC attenuated D-gal-induced cognitive impairment partly via enhancing the antioxidant and anti-inflammatory capacity.

  14. Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia.

    Science.gov (United States)

    Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Tabassum, Saiqa; Madiha, Syeda; Rafiq, Sahar; Tariq, Sumayya; Batool, Tuba Sharf; Saleem, Sadia; Naqvi, Fizza; Perveen, Tahira; Haider, Saida

    2016-01-01

    Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Cognitive enhancement therapy improves fronto-limbic regulation of emotion in alcohol and/or cannabis misusing schizophrenia: a preliminary study

    Directory of Open Access Journals (Sweden)

    Jessica Ann Wojtalik

    2016-01-01

    Full Text Available Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive Enhancement Therapy (CET may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10 or usual care (n = 4 completed post-treatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in fronto-limbic and striatal circuitries which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems.

  16. Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury

    Science.gov (United States)

    2014-01-01

    Background Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with potent anti-inflammatory properties that is extracted from the rhizome Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following TBI. Methods Neurological function, brain water content and cytokine levels were tested in TLR4-/- mice subjected to weight-drop contusion injury. Wild-type (WT) mice were injected intraperitoneally with different concentrations of curcumin or vehicle 15 minutes after TBI. At 24 hours post-injury, the activation of microglia/macrophages and TLR4 was detected by immunohistochemistry; neuronal apoptosis was measured by FJB and TUNEL staining; cytokines were assayed by ELISA; and TLR4, MyD88 and NF-κB levels were measured by Western blotting. In vitro, a co-culture system comprised of microglia and neurons was treated with curcumin following lipopolysaccharide (LPS) stimulation. TLR4 expression and morphological activation in microglia and morphological damage to neurons were detected by immunohistochemistry 24 hours post-stimulation. Results The protein expression of TLR4 in pericontusional tissue reached a maximum at 24 hours post-TBI. Compared with WT mice, TLR4-/- mice showed attenuated functional impairment, brain edema and cytokine release post-TBI. In addition to improvement in the above aspects, 100 mg/kg curcumin treatment post-TBI significantly reduced the number of TLR4-positive microglia/macrophages as well as inflammatory mediator release and neuronal apoptosis in WT mice. Furthermore, Western blot analysis indicated that the levels of TLR4 and its known downstream effectors (MyD88, and NF-κB) were also decreased after curcumin treatment. Similar outcomes were observed in the microglia and

  17. Caspr2 antibody limbic encephalitis is associated with Hashimoto thyroiditis and thymoma.

    Science.gov (United States)

    Lee, Chih-Hong; Lin, Jainn-Jim; Lin, Kun-Ju; Chang, Bao-Luen; Hsieh, Hsiang-Yao; Chen, Wei-Hsun; Lin, Kuang-Lin; Fung, Hon-Chung; Wu, Tony

    2014-06-15

    Contactin-associated protein 2 (Caspr2) antibody is a neuronal surface antibody (NSAb) capable of causing disorders involving central and peripheral nervous systems (PNS). Thymoma can be found in patients with Caspr2 antibodies and is most frequently associated with PNS symptoms. Myasthenia gravis can be found in these patients, but Hashimoto thyroiditis (HT) has not been reported. A 76-year-old woman presented with sub-acute-onset changes in mental status. Further investigations revealed thymoma and HT. The presence of NSAb was tested by immunofluorescence on human embryonic kidney-293 cells. Treatment included corticosteroids, azathioprine, thyroxine, plasmapheresis, and thymectomy. Caspr2 antibody was positive in serum but absent in CSF. Brain magnetic resonance imaging (MRI) showed diffuse cortical atrophy, but did not change significantly after treatments. Brain positron emission tomography (PET) revealed diffuse hypometabolism over the cerebral cortex. The patient's mental status only partially improved. In Caspr2 antibody-associated syndromes, thymoma can occur in patients presenting only with LE, and HT can be an accompanying disease. Brain MRI and PET may not show specific lesions in limbic area. Patients with Caspr2 antibodies and thymoma may not have good prognosis. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-11-22

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

  19. Mapping the brain pathways of traumatic memory: inactivation of protein kinase M zeta in different brain regions disrupts traumatic memory processes and attenuates traumatic stress responses in rats.

    Science.gov (United States)

    Cohen, Hagit; Kozlovsky, Nitsan; Matar, Michael A; Kaplan, Zeev; Zohar, Joseph

    2010-04-01

    Protein kinase M zeta (PKMzeta), a constitutively active isoform of protein kinase C, has been implicated in protein synthesis-dependent maintenance of long-term potentiation and memory storage in the brain. Recent studies reported that local application of ZIP, a membrane-permeant PKMzeta inhibitor, into the insular cortex (IC) of behaving rats abolished long-term memory of taste associations. This study assessed the long-term effects of local applications of ZIP microinjected immediately (1 h) or 10 days after predator scent stress exposure, in a controlled prospectively designed animal model for PTSD. Four brain structures known to be involved in memory processes and in anxiety were investigated: lateral ventricle (LV), dorsal hippocampus (DH), basolateral amygdala and IC. The outcome measures included behavior in an elevated plus maze and acoustic startle response 7 days after microinjection, and freezing behavior upon exposure to trauma-related cue 8 days after microinjection. Previously acquired/encoded memories associated with the IC were also assessed. Inactivation of PKMzeta in the LV or DH within 1h of exposure effectively reduced PTSD-like behavioral disruption and trauma cue response 8 days later. Inactivation of PKMzeta 10 days after exposure had equivalent effects only when administered in the IC. The effect was demonstrated to be specific for trauma memories, whereas previously acquired data were unaffected by the procedure. Predator scent related memories are located in different brain areas at different times beginning with an initial hippocampus-dependent consolidation process, and are eventually stored in the IC. These bring the IC to the forefront as a potential region of significance in processes related to traumatic stress-induced disorders. 2010 Elsevier B.V. and ECNP. All rights reserved.

  20. Cortical-limbic regions modulate depression and anxiety factors in functional dyspepsia. A PET-CT study

    International Nuclear Information System (INIS)

    Liu Mailan; Liang Fanrong; Zeng Fang; Tang Yong; Lan Lei; Song Wenzhong

    2012-01-01

    The objective of this study was to observe some specific brain areas or cerebral functional network participating in the modulation of depression and anxiety factors in functional dyspepsia (FD) patients by detecting cerebral glucose metabolism (CGM) in fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography-computed tomography (PET-CT) scans. Eight FD patients with depression and anxiety (DA-FD group) and eight FD patients without depression and anxiety (non-DA-FD group) were recruited and evaluated by the Nepean Dyspepsia Index (NDI) and Dyspepsia Symptom Scores (DSS). Cerebral 18 F-FDG PET-CT scans were performed on the DA-FD group and non-DA-FD group, respectively. The differences in CGM between the two groups were analyzed with Statistical Parametric Mapping 2.0 (SPM2). Extensive changes in the CGM signals were observed in the cerebral cortex and limbic system of FD patients with depression and anxiety. Compared to non-DA-FD patients, DA-FD patients showed a higher glucose metabolism in the right postcentral gyrus (BA 1 and 5), inferior frontal gyrus (BA 45), superior temporal gyrus (BA 22), middle temporal gyrus (BA 22), inferior parietal lobule (BA 40), lingual gyrus (BA 18) and the left middle occipital gyrus (BA 37), as well as the limbic system including the left thalamus, lateral globus pallidus, parahippocampal gyrus (BA 35), right insular cortex (BA 13) and parahippocampal gyrus (BA 18); a lower glucose metabolism was presented in the left middle cingulated gyrus (BA 24), the right superior frontal gyrus (BA 6), the medial frontal gyrus (BA 6) and middle temporal gyrus (BA 21). An extensive cortical-limbic brain network might modulate the procession of FD patients with depression and anxiety factors. (author)

  1. Genistein attenuates brain damage induced by transient cerebral ischemia through up-regulation of ERK activity in ovariectomized mice.

    Science.gov (United States)

    Wang, Shiquan; Wei, Haidong; Cai, Min; Lu, Yan; Hou, Wugang; Yang, Qianzi; Dong, Hailong; Xiong, Lize

    2014-01-01

    Stroke has severe consequences in postmenopausal women. As replacement therapy of estrogen have various adverse effects and the undermined outcomes. Genistein, a natural phytoestrogen, has been suggested to be a potential neuroprotective agent for such stroke patients. However, the role of genistein and its underlying mechanism in ovariectomized mice has not yet been evaluated. In the present study, ovariectomized mice were treated with genistein (10 mg/kg) or vehicle daily for two weeks before developing transient cerebral ischemia (middle cerebral artery occlusion). The neurological manifestation was evaluated, and infarct volumes were demonstrated by 2,3,5-triphenyltetrazolium chloride staining at 24 h after reperfusion. In addition, phosphorylation of extracellular signal-regulated kinase (ERK) was detected by Western blotting and immunofluorescence staining, and cellular apoptosis was evaluated in the ischemic penumbra. We found that treatment with genistein reduced infarct volumes, improved neurological outcomes and attenuated cellular apoptosis at 24 h after reperfusion. ERK1/2 showed increased phosphorylation by genistein treatment after reperfusion, and an ERK1/2 inhibitor U0126 abolished this protective effect of genistein in terms of infarct volumes, neurological scores and cellular apoptosis. Our findings indicate that treatment with genistein can reduce the severity of subsequent stroke episodes, and that this beneficial function is associated with ERK activation.

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

    Science.gov (United States)

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

    2006-04-15

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

  3. THE BEHAVIOUR AND BRAIN FUNCTION OF THE CICHLID FISH ...

    African Journals Online (AJOL)

    male and female conspecifics on a visual basis. ... Brain Function, Teleost, telencephalon, Cichlid fish behaviour, limbic system, hippocampus. ...... The effects of forebrain ablations on the behaviour of H. philander cannot be satisfactorily.

  4. Swimming attenuates d-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics.

    Science.gov (United States)

    Kou, Xianjuan; Li, Jie; Liu, Xingran; Chang, Jingru; Zhao, Qingxia; Jia, Shaohui; Fan, Jingjing; Chen, Ning

    2017-06-01

    microRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. To explore the regulatory role of miR-34a in aging-related diseases such as Alzheimer's disease (AD) during exercise intervention, we constructed a rat model with d-galactose (d-gal)-induced oxidative stress and cognitive impairment coupled with dysfunctional autophagy and abnormal mitochondrial dynamics, determined the mitigation of cognitive impairment of d-gal-induced aging rats during swimming intervention, and evaluated miR-34a-mediated functional status of autophagy and abnormal mitochondrial dynamics. Meanwhile, whether the upregulation of miR-34a can lead to dysfunctional autophagy and abnormal mitochondrial dynamics was confirmed in human SH-SY5Y cells with silenced miR-34a by the transfection of a miR-34a inhibitor. Results indicated that swimming intervention could significantly attenuate cognitive impairment, prevent the upregulation of miR-34a, mitigate the dysfunctional autophagy, and inhibit the increase of dynamin-related protein 1 (DRP1) in d-gal-induced aging model rats. In contrast, the miR-34a inhibitor in cell model not only attenuated D-gal-induced the impairment of autophagy but also decreased the expression of DRP1 and mitofusin 2 (MFN2). Therefore, swimming training can delay brain aging of d-gal-induced aging rats through attenuating the impairment of miR-34a-mediated autophagy and abnormal mitochondrial dynamics, and miR-34a could be the novel therapeutic target for aging-related diseases such as AD. NEW & NOTEWORTHY In the present study, we have found that the upregulation of miR-34a is the hallmark of aging or aging-related diseases, which can result in dysfunctional autophagy and abnormal mitochondrial dynamics. In contrast, swimming intervention can delay the aging process by rescuing the impaired functional status of autophagy and abnormal mitochondrial dynamics via the suppression of miR-34a. Copyright © 2017 the American Physiological Society.

  5. Magnetic resonance imaging in kainic acid-induced limbic seizure status in cats

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Shigeya; Tanaka, Tatsuya; Fukuda, Hiroshi; Yonemasu, Yukichi [Asahikawa Medical Coll., Hokkaido (Japan); Kondo, Shinji; Hori, Tomokatsu; Tanaka, Mitsuru; Shindo, Kazuyuki

    1993-05-01

    Magnetic resonance imaging before, during, and after kainic acid (KA)-induced limbic seizure status in cats demonstrated the bilateral hippocampi as slightly high-intensity areas on the T[sub 2]-weighted images during the limbic seizure status, and isointensity areas 1-2 weeks after KA injection when the limbic seizure status subsided. However, the hippocampi again became high-intense 1-3 months after KA injection. Histological study suggested that the high-intensity area during the limbic seizure status resulted from regional edema, and in the chronic period from marked gliosis and/or atrophic change as a consequence of tissue damage in the hippocampus. (author).

  6. Brainstem and limbic encephalitis with paraneoplastic neuromyelitis optica.

    Science.gov (United States)

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

    2016-01-01

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

  7. Whole-brain intracranial vessel wall imaging at 3 Tesla using cerebrospinal fluid-attenuated T1-weighted 3D turbo spin echo.

    Science.gov (United States)

    Fan, Zhaoyang; Yang, Qi; Deng, Zixin; Li, Yuxia; Bi, Xiaoming; Song, Shlee; Li, Debiao

    2017-03-01

    Although three-dimensional (3D) turbo spin echo (TSE) with variable flip angles has proven to be useful for intracranial vessel wall imaging, it is associated with inadequate suppression of cerebrospinal fluid (CSF) signals and limited spatial coverage at 3 Tesla (T). This work aimed to modify the sequence and develop a protocol to achieve whole-brain, CSF-attenuated T 1 -weighted vessel wall imaging. Nonselective excitation and a flip-down radiofrequency pulse module were incorporated into a commercial 3D TSE sequence. A protocol based on the sequence was designed to achieve T 1 -weighted vessel wall imaging with whole-brain spatial coverage, enhanced CSF-signal suppression, and isotropic 0.5-mm resolution. Human volunteer and pilot patient studies were performed to qualitatively and quantitatively demonstrate the advantages of the sequence. Compared with the original sequence, the modified sequence significantly improved the T 1 -weighted image contrast score (2.07 ± 0.19 versus 3.00 ± 0.00, P = 0.011), vessel wall-to-CSF contrast ratio (0.14 ± 0.16 versus 0.52 ± 0.30, P = 0.007) and contrast-to-noise ratio (1.69 ± 2.18 versus 4.26 ± 2.30, P = 0.022). Significant improvement in vessel wall outer boundary sharpness was observed in several major arterial segments. The new 3D TSE sequence allows for high-quality T 1 -weighted intracranial vessel wall imaging at 3 T. It may potentially aid in depicting small arteries and revealing T 1 -mediated high-signal wall abnormalities. Magn Reson Med 77:1142-1150, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  8. Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

    International Nuclear Information System (INIS)

    Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye

    2014-01-01

    Highlights: •Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. •Mature BDNF plays an important role in the effects of forced exercise. •Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague–Dawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF–pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF–pCREB signaling in non

  9. Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye, E-mail: dryetian@hotmail.com

    2014-01-10

    Highlights: •Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. •Mature BDNF plays an important role in the effects of forced exercise. •Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague–Dawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF–pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF–pCREB signaling in non

  10. Fingolimod phosphate attenuates oligomeric amyloid β-induced neurotoxicity via increased brain-derived neurotrophic factor expression in neurons.

    Directory of Open Access Journals (Sweden)

    Yukiko Doi

    Full Text Available The neurodegenerative processes that underlie Alzheimer's disease are mediated, in part, by soluble oligomeric amyloid β, a neurotoxic protein that inhibits hippocampal long-term potentiation, disrupts synaptic plasticity, and induces the production of reactive oxygen species. Here we show that the sphingosine-1-phosphate (S1P receptor (S1PR agonist fingolimod phosphate (FTY720-P-a new oral drug for multiple sclerosis-protects neurons against oligomeric amyloid β-induced neurotoxicity. We confirmed that primary mouse cortical neurons express all of the S1P receptor subtypes and FTY720-P directly affects the neurons. Treatment with FTY720-P enhanced the expression of brain-derived neurotrophic factor (BDNF in neurons. Moreover, blocking BDNF-TrkB signaling with a BDNF scavenger, TrkB inhibitor, or ERK1/2 inhibitor almost completely ablated these neuroprotective effects. These results suggested that the neuroprotective effects of FTY720-P are mediated by upregulated neuronal BDNF levels. Therefore, FTY720-P may be a promising therapeutic agent for neurodegenerative diseases, such as Alzheimer's disease.

  11. Attenuation of hypoxic current by intracellular applications of ATP regenerating agents in hippocampal CA1 neurons of rat brain slices.

    Science.gov (United States)

    Chung, I; Zhang, Y; Eubanks, J H; Zhang, L

    1998-10-01

    Hypoxia-induced outward currents (hyperpolarization) were examined in hippocampal CA1 neurons of rat brain slices, using the whole-cell recording technique. Hypoxic episodes were induced by perfusing slices with an artificial cerebrospinal fluid aerated with 5% CO2/95% N2 rather than 5% CO2/95% O2, for about 3 min. The hypoxic current was consistently and reproducibly induced in CA1 neurons dialysed with an ATP-free patch pipette solution. This current manifested as an outward shift in the holding current in association with increased conductance, and it reversed at -78 +/- 2.5 mV, with a linear I-V relation in the range of -100 to -40 mV. To provide extra energy resources to individual neurons recorded, agents were added to the patch pipette solution, including MgATP alone, MgATP + phosphocreatine + creatine kinase, or MgATP + creatine. In CA1 neurons dialysed with patch solutions including these agents, hypoxia produced small outward currents in comparison with those observed in CA1 neurons dialysed with the ATP-free solution. Among the above agents examined, whole-cell dialysis with MgATP + creatine was the most effective at decreasing the hypoxic outward currents. We suggest that the hypoxic hyperpolarization is closely related to energy metabolism in individual CA1 neurons, and that the energy supply provided by phosphocreatine metabolism may play a critical role during transient metabolic stress.

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

    Science.gov (United States)

    Kobayashi, Yasushi

    2017-04-01

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

  13. Are Onconeural Antibodies a Clinical Phenomenology in Paraneoplastic Limbic Encephalitis?

    Directory of Open Access Journals (Sweden)

    Hongliang Zhang

    2013-01-01

    Full Text Available Paraneoplastic neurological syndromes (PNSs occur in patients with cancer and can cause clinical symptoms and signs of dysfunction of the nervous system that are not due to a local effect of the tumor or its metastases. Most of these clinical syndromes in adults are associated with lung cancer, especially small cell lung cancer (SCLC, lymphoma, and gynecological tumors. The finding of highly specific antibodies directed against onconeural antigens has revolutionized the diagnosis and promoted the understanding of these syndromes and led to the current hypothesis of an autoimmune pathophysiology. Accumulating data strongly suggested direct pathogenicity of these antibodies. The field of PNS has expanded rapidly in the past few years with the discovery of limbic encephalitis associated with glutamic acid decarboxylase (GAD 65, the voltage (VGKC-gated potassium channel complex, the methyl (N-NMDA-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, and gamma aminobutyric acid (GABA (B receptors, and so forth. Despite this, the clinical spectrum of these diseases has not yet been fully investigated. The clinical importance of these conditions lies in their frequent response to immunotherapies and, less commonly, their association with distinctive tumors. This review provides an overview on the pathogenesis and diagnosis of PNS, with emphasis on the role of antibodies in limbic encephalitis.

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

    Directory of Open Access Journals (Sweden)

    João Filipe Oliveira

    2013-02-01

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

  15. Abnormal brain activation during threatening face processing in schizophrenia: A meta-analysis of functional neuroimaging studies.

    Science.gov (United States)

    Dong, Debo; Wang, Yulin; Jia, Xiaoyan; Li, Yingjia; Chang, Xuebin; Vandekerckhove, Marie; Luo, Cheng; Yao, Dezhong

    2017-11-15

    Impairment of face perception in schizophrenia is a core aspect of social cognitive dysfunction. This impairment is particularly marked in threatening face processing. Identifying reliable neural correlates of the impairment of threatening face processing is crucial for targeting more effective treatments. However, neuroimaging studies have not yet obtained robust conclusions. Through comprehensive literature search, twenty-one whole brain datasets were included in this meta-analysis. Using seed-based d-Mapping, in this voxel-based meta-analysis, we aimed to: 1) establish the most consistent brain dysfunctions related to threating face processing in schizophrenia; 2) address task-type heterogeneity in this impairment; 3) explore the effect of potential demographic or clinical moderator variables on this impairment. Main meta-analysis indicated that patients with chronic schizophrenia demonstrated attenuated activations in limbic emotional system along with compensatory over-activation in medial prefrontal cortex (MPFC) during threatening faces processing. Sub-task analyses revealed under-activations in right amygdala and left fusiform gyrus in both implicit and explicit tasks. The remaining clusters were found to be differently involved in different types of tasks. Moreover, meta-regression analyses showed brain abnormalities in schizophrenia were partly modulated by age, gender, medication and severity of symptoms. Our results highlighted breakdowns in limbic-MPFC circuit in schizophrenia, suggesting general inability to coordinate and contextualize salient threat stimuli. These findings provide potential targets for neurotherapeutic and pharmacological interventions for schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Deep brain stimulation of the nucleus accumbens shell attenuates cue-induced reinstatement of both cocaine and sucrose seeking in rats.

    Science.gov (United States)

    Guercio, Leonardo A; Schmidt, Heath D; Pierce, R Christopher

    2015-03-15

    Stimuli previously associated with drug taking can become triggers that can elicit craving and lead to relapse of drug-seeking behavior. Here, we examined the influence of deep brain stimulation (DBS) in the nucleus accumbens shell on cue-induced reinstatement of cocaine seeking, an animal model of relapse. Rats were allowed to self-administer cocaine (0.254 mg, i.v.) for 2 h daily for 21 days, with each infusion of cocaine being paired with a cue light. After 21 days of self-administration, cocaine-taking behavior was extinguished by replacing cocaine with saline in the absence of the cue light. Next, during the reinstatement phase, DBS was administered bilaterally into the nucleus accumbens shell through bipolar stainless steel electrodes immediately prior to re-exposure to cues previously associated with cocaine reinforcement. DBS continued throughout the 2 h reinstatement session. Parallel studies examined the influence of accumbens shell DBS on reinstatement induced by cues previously associated with sucrose reinforcement. Results indicated that DBS of the nucleus accumbens shell significantly attenuated cue-induced reinstatement of cocaine and sucrose seeking. Together, these results indicate that DBS of the accumbens shell disrupts cue-induced reinstatement associated with both a drug and a natural reinforcer. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Cerebrospinal Fluid Enhancement on Fluid Attenuated Inversion Recovery Images After Carotid Artery Stenting with Neuroprotective Balloon Occlusions: Hemodynamic Instability and Blood–Brain Barrier Disruption

    International Nuclear Information System (INIS)

    Ogami, Ryo; Nakahara, Toshinori; Hamasaki, Osamu; Araki, Hayato; Kurisu, Kaoru

    2011-01-01

    Purpose: A rare complication of carotid artery stenting (CAS), prolonged reversible neurological symptoms with delayed cerebrospinal fluid (CSF) space enhancement on fluid attenuated inversion recovery (FLAIR) images, is associated with blood–brain barrier (BBB) disruption. We prospectively identified patients who showed CSF space enhancement on FLAIR images. Methods: Nineteen patients—5 acute-phase and 14 scheduled—underwent 21 CAS procedures. Balloon catheters were navigated across stenoses, angioplasty was performed using a neuroprotective balloon, and stents were placed with after dilation under distal balloon protection. CSF space hyperintensity or obscuration on FLAIR after versus before CAS indicated CSF space enhancement. Correlations with clinical factors were examined. Results: CSF space was enhanced on FLAIR in 12 (57.1%) cases. Postprocedural CSF space enhancement was significantly related to age, stenosis rate, acute-stage procedure, and total occlusion time. All acute-stage CAS patients showed delayed enhancement. Only age was associated with delayed CSF space enhancement in scheduled CAS patients. Conclusions: Ischemic intolerance for severe carotid artery stenosis and temporary neuroprotective balloon occlusion, causing reperfusion injury, seem to be the main factors that underlie BBB disruption with delayed CSF space enhancement shortly after CAS, rather than sudden poststenting hemodynamic change. Our results suggest that factors related to hemodynamic instability or ischemic intolerance seem to be associated with post-CAS BBB vulnerability. Patients at risk for hemodynamic instability or with ischemic intolerance, which decrease BBB integrity, require careful management to prevent intracranial hemorrhagic and other post-CAS complications.

  18. Enhanced attenuation of meningeal inflammation and brain edema by concomitant administration of anti-CD18 monoclonal antibodies and dexamethasone in experimental Haemophilus meningitis.

    Science.gov (United States)

    Sáez-Llorens, X; Jafari, H S; Severien, C; Parras, F; Olsen, K D; Hansen, E J; Singer, I I; McCracken, G H

    1991-12-01

    Antiinflammatory therapy has been shown to reduce the adverse pathophysiological consequences that occur in bacterial meningitis and to improve outcome from disease. In the present study, modulation of two principal steps of the meningeal inflammatory cascade was accomplished by concomitant administration of dexamethasone to diminish overproduction of cytokines in response to a bacterial stimulus and of a monoclonal antibody directed against adhesion-promoting receptors on leukocytes to inhibit recruitment of white blood cells into the subarachnoid space. Dexamethasone and antibody therapy produced a marked attenuation of all indices of meningeal inflammation and reduction of brain water accumulation after H. influenzae-induced meningitis in rabbits compared with results of each agent given alone and of untreated animals. In addition, the enhanced host's meningeal inflammatory reaction that follows antibiotic-induced bacterial lysis was profoundly ameliorated when dual therapy was administered without affecting clearance rates of bacteria from cerebrospinal fluid and vascular compartments. The combination of both therapeutic approaches may offer a promising mode of treatment to improve further the outcome from bacterial meningitis.

  19. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

    Energy Technology Data Exchange (ETDEWEB)

    Chan, Ming-Huan [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Institute of Neuroscience, National Changchi University, Taipei, Taiwan (China); Chung, Shiang-Sheng [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Department of Pharmacy, Yuli Veterans Hospital, Hualien, Taiwan (China); Stoker, Astrid K.; Markou, Athina [Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (United States); Chen, Hwei-Hsien, E-mail: hwei@nhri.org.tw [Department of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan (China); Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan (China)

    2012-12-01

    Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene

  20. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

    International Nuclear Information System (INIS)

    Chan, Ming-Huan; Chung, Shiang-Sheng; Stoker, Astrid K.; Markou, Athina; Chen, Hwei-Hsien

    2012-01-01

    Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene

  1. Probucol plus cilostazol attenuate hypercholesterolemia‑induced exacerbation in ischemic brain injury via anti-inflammatory effects.

    Science.gov (United States)

    Kim, Ji Hyun; Hong, Ki Whan; Bae, Sun Sik; Shin, Yong-Il; Choi, Byung Tae; Shin, Hwa Kyoung

    2014-09-01

    Probucol, a lipid-lowering agent with anti-oxidant properties, is involved in protection against atherosclerosis, while cilostazol, an antiplatelet agent, has diverse neuroprotective properties. In this study, we investigated the anti-inflammatory effects of probucol and cilostazol on focal cerebral ischemia with hypercholesterolemia. Apolipoprotein E (ApoE) knockout (KO) mice were fed a high-fat diet (HFD) with or without 0.3% probucol and/or 0.2% cilostazol for 10 weeks. To assess the protective effects of the combined therapy of probucol and cilostazol on ischemic injury, the mice received 40 min of middle cerebral artery occlusion (MCAO). Infarct volumes, neurobehavioral deficits and neuroinflammatory mediators were subsequently evaluated 48 h after reperfusion. Probucol alone and probucol plus cilostazol significantly decreased total- and low-density lipoprotein (LDL)-cholesterol in ApoE KO with HFD. MCAO resulted in significantly larger infarct volumes in ApoE KO mice provided with HFD compared to those fed a regular diet, although these volumes were significantly reduced in the probucol plus cilostazol group. Consistent with a smaller infarct size, probucol alone and the combined treatment of probucol and cilostazol improved neurological and motor function. In addition, probucol alone and probucol plus cilostazol decreased MCP-1 expression and CD11b and GFAP immuno-reactivity in the ischemic cortex. These findings suggested that the inhibitory effects of probucol plus cilostazol in MCP-1 expression in the ischemic brain with hypercholesterolemia allowed the identification of one of the mechanisms responsible for anti-inflammatory action. Probucol plus cilostazol may therefore serve as a therapeutic strategy for reducing the impact of stroke in hypercholesterolemic subjects.

  2. Attenuating Nicotine Reinforcement and Relapse by Enhancing Endogenous Brain Levels of Kynurenic Acid in Rats and Squirrel Monkeys.

    Science.gov (United States)

    Secci, Maria E; Auber, Alessia; Panlilio, Leigh V; Redhi, Godfrey H; Thorndike, Eric B; Schindler, Charles W; Schwarcz, Robert; Goldberg, Steven R; Justinova, Zuzana

    2017-07-01

    The currently available antismoking medications have limited efficacy and often fail to prevent relapse. Thus, there is a pressing need for newer, more effective treatment strategies. Recently, we demonstrated that enhancing endogenous levels of kynurenic acid (KYNA, a neuroinhibitory product of tryptophan metabolism) counteracts the rewarding effects of cannabinoids by acting as a negative allosteric modulator of α7 nicotinic receptors (α7nAChRs). As the effects of KYNA on cannabinoid reward involve nicotinic receptors, in the present study we used rat and squirrel monkey models of reward and relapse to examine the possibility that enhancing KYNA can counteract the effects of nicotine. To assess specificity, we also examined models of cocaine reward and relapse in monkeys. KYNA levels were enhanced by administering the kynurenine 3-monooxygenase (KMO) inhibitor, Ro 61-8048. Treatment with Ro 61-8048 decreased nicotine self-administration in rats and monkeys, but did not affect cocaine self-administration. In rats, Ro 61-8048 reduced the ability of nicotine to induce dopamine release in the nucleus accumbens shell, a brain area believed to underlie nicotine reward. Perhaps most importantly, Ro 61-8048 prevented relapse-like behavior when abstinent rats or monkeys were reexposed to nicotine and/or cues that had previously been associated with nicotine. Ro 61-8048 was also effective in monkey models of cocaine relapse. All of these effects of Ro 61-8048 in monkeys, but not in rats, were reversed by pretreatment with a positive allosteric modulator of α7nAChRs. These findings suggest that KMO inhibition may be a promising new approach for the treatment of nicotine addiction.

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

    LENUS (Irish Health Repository)

    2011-01-01

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

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

    Science.gov (United States)

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

    2017-07-07

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

  5. Impaired white matter connections of the limbic system networks associated with impaired emotional memory in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Xiaoshu Li

    2016-10-01

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

  6. Electroconvulsive therapy in a pediatric patient with malignant catatonia and paraneoplastic limbic encephalitis.

    Science.gov (United States)

    Lee, Andrew; Glick, David B; Dinwiddie, Stephen H

    2006-12-01

    Paraneoplastic limbic encephalitis is a rare disorder that can cause memory loss, confusion, personality change, cognitive dysfunction, and psychosis. We present a case of an 11-year-old girl who was successfully treated with electroconvulsive therapy for a catatonic state associated with paraneoplastic limbic encephalitis caused by an ovarian teratoma.

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

    Science.gov (United States)

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

    2014-07-01

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

  8. RESOLUTE PET/MRI Attenuation Correction for O-(2-18F-fluoroethyl-L-tyrosine (FET in Brain Tumor Patients with Metal Implants

    Directory of Open Access Journals (Sweden)

    Claes N. Ladefoged

    2017-08-01

    Full Text Available Aim: Positron emission tomography (PET imaging is a useful tool for assisting in correct differentiation of tumor progression from reactive changes, and the radiolabeled amino acid analog tracer O-(2-18F-fluoroethyl-L-tyrosine (FET-PET is amongst the most frequently used. The FET-PET images need to be quantitatively correct in order to be used clinically, which require accurate attenuation correction (AC in PET/MRI. The aim of this study was to evaluate the use of the subject-specific MR-derived AC method RESOLUTE in post-operative brain tumor patients.Methods: We analyzed 51 post-operative brain tumor patients (68 examinations, 200 MBq [18F]-FET investigated in a PET/MRI scanner. MR-AC maps were acquired using: (1 the Dixon water fat separation sequence, (2 the ultra short echo time (UTE sequences, (3 calculated using our new RESOLUTE methodology, and (4 a same day low-dose CT used as reference “gold standard.” For each subject and each AC method the tumor was delineated by isocontouring tracer uptake above a tumor(T-to-brain background (B activity ratio of 1.6. We measured B, tumor mean and maximal activity (TMEAN, TMAX, biological tumor volume (BTV, and calculated the clinical metrics TMEAN/B and TMAX/B.Results: When using RESOLUTE 5/68 studies did not meet our predefined acceptance criteria of TMAX/B difference to CT-AC < ±0.1 or 5%, TMEAN/B < ±0.05 or 5%, and BTV < ±2 mL or 10%. In total, 46/68 studies failed our acceptance criteria using Dixon, and 26/68 using UTE. The 95% limits of agreement for TMAX/B was for RESOLUTE (−3%; 4%, Dixon (−9%; 16%, and UTE (−7%; 10%. The absolute error when measuring BTV was 0.7 ± 1.9 mL (N.S with RESOLUTE, 5.3 ± 10 mL using Dixon, and 1.7 ± 3.7 mL using UTE. RESOLUTE performed best in the identification of the location of peak activity and in brain tumor follow-up monitoring using clinical FET PET metrics.Conclusions: Overall, we found RESOLUTE to be the AC method that most robustly

  9. A multi-centre evaluation of eleven clinically feasible brain PET/MRI attenuation correction techniques using a large cohort of patients.

    Science.gov (United States)

    Ladefoged, Claes N; Law, Ian; Anazodo, Udunna; St Lawrence, Keith; Izquierdo-Garcia, David; Catana, Ciprian; Burgos, Ninon; Cardoso, M Jorge; Ourselin, Sebastien; Hutton, Brian; Mérida, Inés; Costes, Nicolas; Hammers, Alexander; Benoit, Didier; Holm, Søren; Juttukonda, Meher; An, Hongyu; Cabello, Jorge; Lukas, Mathias; Nekolla, Stephan; Ziegler, Sibylle; Fenchel, Matthias; Jakoby, Bjoern; Casey, Michael E; Benzinger, Tammie; Højgaard, Liselotte; Hansen, Adam E; Andersen, Flemming L

    2017-02-15

    To accurately quantify the radioactivity concentration measured by PET, emission data need to be corrected for photon attenuation; however, the MRI signal cannot easily be converted into attenuation values, making attenuation correction (AC) in PET/MRI challenging. In order to further improve the current vendor-implemented MR-AC methods for absolute quantification, a number of prototype methods have been proposed in the literature. These can be categorized into three types: template/atlas-based, segmentation-based, and reconstruction-based. These proposed methods in general demonstrated improvements compared to vendor-implemented AC, and many studies report deviations in PET uptake after AC of only a few percent from a gold standard CT-AC. Using a unified quantitative evaluation with identical metrics, subject cohort, and common CT-based reference, the aims of this study were to evaluate a selection of novel methods proposed in the literature, and identify the ones suitable for clinical use. In total, 11 AC methods were evaluated: two vendor-implemented (MR-AC DIXON and MR-AC UTE ), five based on template/atlas information (MR-AC SEGBONE (Koesters et al., 2016), MR-AC ONTARIO (Anazodo et al., 2014), MR-AC BOSTON (Izquierdo-Garcia et al., 2014), MR-AC UCL (Burgos et al., 2014), and MR-AC MAXPROB (Merida et al., 2015)), one based on simultaneous reconstruction of attenuation and emission (MR-AC MLAA (Benoit et al., 2015)), and three based on image-segmentation (MR-AC MUNICH (Cabello et al., 2015), MR-AC CAR-RiDR (Juttukonda et al., 2015), and MR-AC RESOLUTE (Ladefoged et al., 2015)). We selected 359 subjects who were scanned using one of the following radiotracers: [ 18 F]FDG (210), [ 11 C]PiB (51), and [ 18 F]florbetapir (98). The comparison to AC with a gold standard CT was performed both globally and regionally, with a special focus on robustness and outlier analysis. The average performance in PET tracer uptake was within ±5% of CT for all of the proposed

  10. Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates

    Science.gov (United States)

    Ances, Beau M.; Vitaliani, Roberta; Taylor, Robert A.; Liebeskind, David S.; Voloschin, Alfredo; Houghton, David J.; Galetta, Steven L.; Dichter, Marc; Alavi, Abass; Rosenfeld, Myrna R.; Dalmau, Josep

    2007-01-01

    We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [18F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens

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

    Science.gov (United States)

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

    2018-06-01

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

  12. Paraneoplastic limbic encephalitis as a cause of new onset of seizures in a patient with non-small cell lung carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Voutsas Vasileios

    2008-08-01

    Full Text Available Abstract Introduction The etiology of seizure disorders in lung cancer patients is broad and includes some rather rare causes of seizures which can sometimes be overlooked by physicians. Paraneoplastic limbic encephalitis is a rather rare cause of seizures in lung cancer patients and should be considered in the differential diagnosis of seizure disorders in this population. Case presentation This case report describes the new onset of seizures in a 64-year-old male patient receiving chemotherapy for a diagnosed stage IV non-small cell lung carcinoma. After three cycles of therapy, he was re-evaluated with a chest computed tomography which showed a 50% reduction in the tumor mass and in the size of the hilar and mediastinal lymphadenopathy. Twenty days after the fourth cycle of chemotherapy, the patient was admitted to a neurological clinic because of the onset of self-limiting complex partial seizures, with motionless stare and facial twitching, but with no signs of secondary generalization. The patient had also recently developed neurological symptoms of short-term memory loss and temporary confusion, and behavioral changes. Laboratory evaluation included brain magnetic resonance imaging, magnetic resonance spectroscopy of the brain, serum examination for 'anti-Hu' antibodies and stereotactic brain biopsy. Based on the clinical picture, the patient's history of lung cancer, the brain magnetic resonance imaging findings and the results of the brain biopsy, we concluded that our patient had a 'definite' diagnosis of paraneoplastic limbic encephalitis and he was subsequently treated with a combination of chemotherapy and oral steroids, resulting in stabilization of his neurological status. Despite the neurological stabilization, a chest computed tomography which was performed after the 6th cycle showed relapse of the disease in the chest. Conclusion Paraneoplastic limbic encephalitis is a rather rare cause of new onset of seizures in patients with

  13. Possible anti-VGKC autoimmune limbic encephalitis associated with SIADH.

    Science.gov (United States)

    Black, Nicholas; Hamada, Hazim

    2018-03-07

    An 80-year-old woman presented with a 5-week history of increasing confusion. Examination was remarkable only for deficits in short-term memory and paranoid thoughts. Blood tests revealed hyponatraemia, and further biochemical testing was consistent with syndrome of inappropriate antidiuretic hormone (SIADH). After an exhaustive diagnostic workup for causes of SIADH, the only abnormal finding was a mildly raised antivoltage-gated potassium channel (VGKC) titre of 185 pmol/L (0-69) consistent with possible anti-VGKC autoimmune limbic encephalitis. However, other diagnostic features were absent. She is currently undergoing outpatient investigation for other causes of memory loss. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

    Science.gov (United States)

    Yamamoto, Tomotaka; Tsuji, Shoji

    2010-08-01

    Anti-Ma2-associated encephalitis (or anti-Ma2 encephalitis) is a paraneoplastic neurological syndrome (PNS) characterized by isolated or combined limbic, diencephalic, or brainstem dysfunction. Anti-Ma2 antibodies detected in the serum or cerebrospinal fluid of patients are highly specific for this disease entity and belong to a group of well-characterized onconeuronal antibodies (or classical antibodies). The corresponding antigen, Ma2 is selectively expressed intracellularly in neurons and tumors as is the case with other onconeuronal antigens targeted by classical antibodies. However, in most cases the clinical pictures are different from those of classical PNS and this creates a potential risk of underdiagnosis. Although limbic dysfunction is the most common manifestation in patients with anti-Ma2 encephalitis which is one of the major causes of paraneoplastic limbic encephalitis (LE), it has been reported that less than 30% of the patients with anti-Ma2 LE exhibit clinical presentations typical of the classical description of LE. Of the remaining, many exhibit excessive daytime sleepiness, vertical ophthalmoparesis, or both associated with LE, because of frequent involvement of the diencephalon and/or upper brainstem. Anti-Ma2 LE can also be manifested as a pure psychiatric disturbance such as obsessive-compulsive disorder in a few cases. Some patients develop mesodiencephalic encephalitis with minor involvement of the limbic system, and some may manifest severe hypokinesis. About 40% of the patients with anti-Ma2 antibodies also have antibodies against different epitopes on Ma1, a homologue of Ma2. These patients may have predominant cerebellar and/or brainstem dysfunctions due to more extensive involvement of subtentorial structures. Anti-Ma2 encephalitis is outstanding among other PNS associated with classical antibodies in that the response rate to treatment is relatively high. While it can cause severe neurological deficits or death in a substantial

  15. Alcoholism and dampened temporal limbic activation to emotional faces.

    Science.gov (United States)

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

    2009-11-01

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

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

    Science.gov (United States)

    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 (stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Hypothermia due to limbic system involvement and longitudinal myelitis in a case of Japanese encephalitis: a case report from India

    Directory of Open Access Journals (Sweden)

    Narayanan S

    2017-04-01

    Full Text Available Santhosh Narayanan,1 NK Thulaseedharan,1 Gomathy Subramaniam,2 Geetha Panarkandy,1 VK Shameer,1 Arathi Narayanan1 1Department of General Medicine, 2Department of Radiodiagnosis, Government Medical College, Kozhikode, Kerala, India Abstract: Japanese encephalitis (JE is an infectious encephalitis prevalent in Asia. It usually presents with fever, headache, convulsions and extrapyramidal symptoms. Limbic system involvement and hypothermia though common in autoimmune encephalitis have never been reported in JE. We report a case of an 18-year-old girl with no previous comorbidities who presented to us with a history of fever and headache for 1 week duration. She developed bilateral lateral rectus palsy and asymmetric flaccid weakness of all four limbs, after 2 days of admission, which was followed by altered sensorium and intermittent hypothermia. Neuroimaging revealed longitudinal myelitis extending from pons till the L1 level along with bilateral thalamic hemorrhage in brain. Cerebrospinal fluid (CSF was positive for IgM antibody to JE virus. She was treated with supportive measures, but she developed intractable hypothermia and seizures and succumbed to illness after 2 weeks of admission. Keywords: Japanese encephalitis, hypothermia, limbic system

  18. Three-dimensional fluid-attenuated inversion recovery sequence for visualisation of subthalamic nucleus for deep brain stimulation in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Heo, Young Jin [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology, Research Institute of Radiology, Seoul (Korea, Republic of); Inje University, Department of Radiology, Busan Paik Hospital, Busan (Korea, Republic of); Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology, Research Institute of Radiology, Seoul (Korea, Republic of); Lee, Jung Kyo [University of Ulsan College of Medicine, Asan Medical Center, Department of Neurosurgery, Seoul (Korea, Republic of); Lee, Chong Sik; Chung, Sun J. [University of Ulsan College of Medicine, Asan Medical Center, Department of Neurology, Seoul (Korea, Republic of); Cho, So Hyun [Department of Radiology, Busan (Korea, Republic of); Lee, Gyoung Ro [Philips HealthCare Korea, Seoul (Korea, Republic of)

    2015-09-15

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an accepted treatment for advanced Parkinson's disease (PD). However, targeting the STN is difficult due to its relatively small size and variable location. The purpose of this study was to assess which of the following sequences obtained with the 3.0 T MR system can accurately delineate the STN: coronal 3D fluid-attenuated inversion recovery (FLAIR), 2D T2*-weighted fast-field echo (T2*-FFE) and 2D T2-weighted turbo spin-echo (TSE) sequences. We included 20 consecutive patients with PD who underwent 3.0 T MR for DBS targeting. 3D FLAIR, 2D T2*-FFE and T2-TSE images were obtained for all study patients. Image quality and demarcation of the STN were analysed using 4-point scales, and contrast ratio (CR) of the STN and normal white matter was calculated. The Friedman test was used to compare the three sequences. In qualitative analysis, the 2D T2*-FFE image showed more artefacts than 3D FLAIR or 2D T2-TSE, but the difference did not reach statistical significance. 3D FLAIR images showed significantly superior demarcation of the STN compared with 2D T2*-FFE and T2-TSE images (P < 0.001, respectively). The CR of 3D FLAIR was significantly higher than that of 2D T2*-FFE or T2-TSE images in multiple comparison correction (P < 0.001), but there was no significant difference in the CR between 2D T2*-FFE and T2-TSE images. Coronal 3D FLAIR images showed the most accurate demarcation of the STN for DBS targeting among coronal 3D FLAIR, 2D T2*-FFE and T2-TSE images. (orig.)

  19. T1-weighted fluid-attenuated inversion recovery and T1-weighted fast spin-echo contrast-enhanced imaging: a comparison in 20 patients with brain lesions

    International Nuclear Information System (INIS)

    Al-Saeed, O.; Athyal, R. P.; Ismail, M.; Rudwan, M.; Khafajee, S.

    2009-01-01

    Full text: Tl-weighted fluid-attenuated inversion recovery (FLAIR) sequence is a relatively new pulse sequence for intracranial MR imaging. This study was performed to compare the image quality of Tl-weighted FLAIR with the Tl-weighted FSE sequence. Twenty patients with brain lesions underwent Tl-weighted fast spin-echo (FSE) and Tl-weighted FLAIR during the same imaging session. Four quantitative and three qualitative criteria were used to compare the two sequences after contrast. Two of four quantitative criteria pertained to lesion characteristics: lesion to white matter (WM) contrast-to-noise ratio (CNR) and lesion to cerebrospinal fluid (CSF) CNR, and two related to signals from normal tissue: grey matter to WM CNR and WM to CSF CNR. The three qualitative criteria were conspicuousness of the lesion, the presence of image artefacts and the overall image contrast. Both Tl-weighted FSE and FLAIR images were effective in demonstrating lesions. Image contrast was superior in Tl-weighted FLAIR images with significantly improved grey matter-WM CNRs and CSF-WM CNRs. The overall image contrast was judged to be superior on Tl-weighted FLAIR images compared with Tl-weighted FSE images by all neuroradiologists. Two of three reviewers considered that the FLAIR images had slightly increased imaging artefacts that, however, did not interfere with image interpretation. Tl-weighted FLAIR imaging provides improved lesion-to-background and grey to WM contrast-to-noise ratios. Superior conspicuity of lesions and overall image contrast is obtained in comparable acquisition times. These indicate an important role for Tl-weighted FLAIR in intracranial imaging and highlight its advantage over the more widely practiced Tl-weighted FSE sequence

  20. Three-dimensional fluid-attenuated inversion recovery sequence for visualisation of subthalamic nucleus for deep brain stimulation in Parkinson's disease

    International Nuclear Information System (INIS)

    Heo, Young Jin; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Jung, Seung Chai; Lee, Jung Kyo; Lee, Chong Sik; Chung, Sun J.; Cho, So Hyun; Lee, Gyoung Ro

    2015-01-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an accepted treatment for advanced Parkinson's disease (PD). However, targeting the STN is difficult due to its relatively small size and variable location. The purpose of this study was to assess which of the following sequences obtained with the 3.0 T MR system can accurately delineate the STN: coronal 3D fluid-attenuated inversion recovery (FLAIR), 2D T2*-weighted fast-field echo (T2*-FFE) and 2D T2-weighted turbo spin-echo (TSE) sequences. We included 20 consecutive patients with PD who underwent 3.0 T MR for DBS targeting. 3D FLAIR, 2D T2*-FFE and T2-TSE images were obtained for all study patients. Image quality and demarcation of the STN were analysed using 4-point scales, and contrast ratio (CR) of the STN and normal white matter was calculated. The Friedman test was used to compare the three sequences. In qualitative analysis, the 2D T2*-FFE image showed more artefacts than 3D FLAIR or 2D T2-TSE, but the difference did not reach statistical significance. 3D FLAIR images showed significantly superior demarcation of the STN compared with 2D T2*-FFE and T2-TSE images (P < 0.001, respectively). The CR of 3D FLAIR was significantly higher than that of 2D T2*-FFE or T2-TSE images in multiple comparison correction (P < 0.001), but there was no significant difference in the CR between 2D T2*-FFE and T2-TSE images. Coronal 3D FLAIR images showed the most accurate demarcation of the STN for DBS targeting among coronal 3D FLAIR, 2D T2*-FFE and T2-TSE images. (orig.)

  1. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients: role of enhanced brain reward functional connectivity and homeostasis redeeming joy.

    Science.gov (United States)

    McLaughlin, Thomas; Blum, Kenneth; Oscar-Berman, Marlene; Febo, Marcelo; Agan, Gozde; Fratantonio, James L; Simpatico, Thomas; Gold, Mark S

    2015-06-01

    Lucid dreams are frequently pleasant and training techniques have been developed to teach dreamers to induce them. In addition, the induction of lucid dreams has also been used as a way to ameliorate nightmares. On the other hand, lucid dreams may be associated with psychiatric conditions, including Post-Traumatic Stress Disorder (PTSD) and Reward Deficiency Syndrome-associated diagnoses. In the latter conditions, lucid dreams can assume an unpleasant and frequently terrifying character. We present two cases of dramatic alleviation of terrifying lucid dreams in patients with PTSD. In the first case study, a 51-year-old, obese woman, diagnosed with PTSD and depression, had attempted suicide and experienced terrifying lucid nightmares linked to sexual/physical abuse from early childhood by family members including her alcoholic father. Her vivid "bad dreams" remained refractory in spite of 6 months of treatment with Dialectical Behavioral Therapy (DBT) and standard pharmaceutical agents which included prazosin, clonidie and Adderall. The second 39-year-old PTSD woman patient had also suffered from lucid nightmares. The medication visit notes reveal changes in the frequency, intensity and nature of these dreams after the complex putative dopamine agonist KB220Z was added to the first patient's regimen. The patient reported her first experience of an extended period of happy dreams. The second PTSD patient, who had suffered from lucid nightmares, was administered KB220Z to attenuate methadone withdrawal symptoms and incidentally reported dreams full of happiness and laughter. These cases are discussed with reference to the known effects of KB220Z including enhanced dopamine homeostasis and functional connectivity of brain reward circuitry in rodents and humans. Their understanding awaits intensive investigation involving large-population, double-blinded studies.

  2. Deep brain stimulation of the nucleus basalis of Meynert attenuates early EEG components associated with defective sensory gating in patients with Alzheimer disease - a two-case study.

    Science.gov (United States)

    Dürschmid, Stefan; Reichert, Christoph; Kuhn, Jens; Freund, Hans-Joachim; Hinrichs, Hermann; Heinze, Hans-Jochen

    2017-10-20

    Alzheimer's disease (AD) is associated with deterioration of memory and cognitive function and a degeneration of neurons of the nucleus basalis of Meynert (NBM). The NBM is the major input source of acetylcholine (ACh) to the cortex. The decreasing cholinergic innervation of the cortex due to degeneration of the NBM might be the cause of loss of memory function. NBM-Deep brain stimulation (NBM-DBS) is considered to serve as a potential therapeutic option for patients with AD by supporting residual cholinergic transmission to stabilize oscillatory activity in memory-relevant circuits. However, whether DBS could improve sensory memory functions in patients with AD is not clear. Here, in a passive auditory oddball paradigm, patients with AD (N = 2) listened to repetitive background tones (standard tones) randomly interrupted by frequency deviants in two blocks with NBM-DBS OFF and then NBM-DBS ON, while age-matched healthy controls (N = 6) repeated the experiment twice. The mismatch negativity in NBM-DBS OFF significantly differed from controls in both blocks, but not under NBM-DBS, which was likely due to a pronounced P50 increase overlapping with the N1 in NBM-DBS OFF. This early complex of EEG components recovered under stimulation to a normal level as defined by responses in controls. In this temporal interval, we found in patients with NBM-DBS ON (but not with NBM-DBS OFF) and in controls a strong repetition suppression effect to standard tones - with more attenuated responses to frequently repeated standard tones. This highlights the role of NBM-DBS for sensory gating of familiar auditory information into sensory memory. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. Successful treatment of acute autoimmune limbic encephalitis with negative VGKC and NMDAR antibodies.

    Science.gov (United States)

    Modoni, Anna; Masciullo, Marcella; Spinelli, Pietro; Marra, Camillo; Tartaglione, Tommaso; Andreetta, Francesca; Tonali, Pietro; Silvestri, Gabriella

    2009-03-01

    To describe a case of acute nonherpetic limbic encephalitis (LE) with negative testing for antibodies directed against onconeuronal and cell membrane antigens, including voltage-gated potassium channels and N-methyl-D-aspartate receptor, that showed a dramatic response to immune therapy. A 30-year-old woman manifested generalized seizures, altered consciousness, and memory impairment shortly after a prodromal viral illness. Few days later the patient developed a drug-resistant epileptic status. Electroencephalograph showed bitemporal slowing and paroxysmal slow wave bursts. Brain magnetic resonance imaging showed bilateral swelling in the medial temporal lobes. Cerebrospinal fluid analysis ruled out viral etiologies. A diagnostic search for cancer, including serum testing for known onconeuronal antibodies proved negative. Screening for cell membrane antigen antibodies, including voltage-gated potassium channels and N-methyl-D-aspartate receptor, was also negative. Suspecting an autoimmune etiology, we started an immunomodulatory treatment with intravenous immunoglobulin followed by a short course of oral prednisone, obtaining a full clinical recovery. Our report confirms previous observations of "seronegative" autoimmune LE, suggesting the presence of other, still unknown central nervous system antigens representing a target of a postinfectious, autoimmune response in these patients. Moreover, it emphasizes the importance of early recognition and treatment of acute autoimmune LE, to reduce the risk of intensive care unit-related complications and the occurrence of permanent cognitive or behavioral defects.

  4. An effective immunotherapy regimen for VGKC antibody-positive limbic encephalitis.

    Science.gov (United States)

    Wong, S H; Saunders, M D; Larner, A J; Das, K; Hart, I K

    2010-10-01

    Voltage-gated potassium channel antibody-positive limbic encephalitis (VGKC+LE) frequently improves with immunotherapy, although the optimum regimen is unknown. The effectiveness of a combination immunomodulatory regimen was tested in consecutive VGKC+LE patients. This was an open-label prospective study of nine VGKC+LE patients. All patients had plasma exchange (50 ml/kg), intravenous immunoglobulin (2 g/kg) and intravenous methylprednisolone (1 g×3), followed by maintenance oral prednisolone (1 mg/kg/day). Mycophenolate (2 g/day) was used in the first three patients. Assessments included serial clinical, cognitive, brain MRI and VGKC antibody testing. Within 1 week, seizures and hyponatraemia remitted in all affected patients. Cognitive function improved in all patients within 3 months. MRI appearances improved substantially within 9 months, with remission of inflammation in the majority of patients. All achieved immunological remission with normal VGKC antibody titres within 1-4 months. Major adverse events of therapy included one septicaemia and one thrombosis on plasma exchange and one death from sepsis after incidental bowel surgery. One patient remains in remission after 40 months of follow up, 26 months after being off all treatment. Our immunotherapy regimen was effective for the treatment of the clinical, cognitive and immunological features of VGKC+LE. Radiological improvement was seen in the majority. Pending randomised controlled trials, this regimen is proposed for the treatment of VGKC+LE.

  5. Imaging of limbic para-neoplastic encephalitis; Imagerie de l`encephalite limbique paraneoplastique

    Energy Technology Data Exchange (ETDEWEB)

    Rimmelin, A.; Sellat, F.; Morand, G.; Quoix, E.; Clouet, P.L.; Dietemann, J.L. [Centre Hospitalier Universitaire, 67 - Strasbourg (France)

    1997-09-01

    Para-neoplastic limbic encephalitis is a rare syndrome mostly associated with small cell lung cancer. We present the case of a 69-year-old man with selective amnesia suggesting limbic encephalitis. A neuroendocrine cell lung cancer was found, confirming the diagnostics of para-neoplastic limbic encephalitis. Contrast-enhanced cerebral CT was normal whether magnetic resonance imaging showed signal abnormalities of the medial part of temporal lobes and hippocampal regions. Because neurologic improvement may follow treatment of the primary tumor, early diagnosis is important. (authors). 10 refs.

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

    Science.gov (United States)

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

    2000-08-01

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

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

    Science.gov (United States)

    Radja, Guirindhra Koumar; Cavanna, Andrea Eugenio

    2013-01-01

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

  8. Orbitofrontal and limbic signatures of empathic concern and intentional harm in the behavioral variant frontotemporal dementia.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  10. Limbic Encephalitis in Taiwanese Children and Adolescence: A Single Center Study

    Directory of Open Access Journals (Sweden)

    I-Jun Chou

    2013-08-01

    Conclusion: This study provides evidence for a potential association between antibodies and limbic encephalitis. The presence of antibodies, especially antibodies to GAD, may serve as an indicator for immunotherapy.

  11. Pitfalls in diagnosing limbic encephalitis - a case report.

    Science.gov (United States)

    Kerling, F; Blümcke, I; Stefan, H

    2008-11-01

    The syndrome of limbic encephalitis (LE) is characterized by subacute onset of temporal lobe epilepsy, loss of short-term memory, cognitive confusion and psychiatric symptoms. We report a patient with pharmacoresistant epilepsy who underwent presurgical video-electroencephalogram (EEG)-monitoring with normal psychiatric and neuropsychological findings. Magnetic resonance imaging (MRI) revealed a hyperintense lesion within the right amygdala but no contrast enhancement. Analysis of cerebrospinal fluid (CSF) showed pleocytosis and positive oligoclonal bands, but all tests for neurotropic viruses or borrelia antibodies were negative. Presurgical evaluation identified a right mesiotemporal focus. As a tumour was the most likely differential diagnosis, we performed selective amygdalohippocampectomy of the right hemisphere. Subsequent histopathological examination revealed the surprising diagnosis of LE. As a consequence, tumour screening was initiated and a testicular carcinoma with high anti-Ma2-antibody titres was detected. Following surgical and chemotherapeutical treatment, the patient was seizure-free and Ma2-antibodies decreased below detection limits. Conclusion - This case report highlights that LE has to be considered even in patients with atypical clinical presentation, i.e. without neuropsychological deficits, if CSF analysis reveals an inflammatory response. When LE is diagnosed, extensive tumour search is mandatory to detect and treat the paraneoplastic origin of LE. Therapeutic strategies of LE include surgical treatment as well as early immunosuppression.

  12. Intranasal administration of vitamin D attenuates blood-brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Enkhjargal, Budbazar; McBride, Devin W; Manaenko, Anatol; Reis, Cesar; Sakai, Yasushi; Tang, Jiping; Zhang, John H

    2017-07-01

    In this study, we investigated the role of vitamin D3 (VitD3) on endogenous osteopontin (OPN), a neuroprotective glycoprotein, after subarachnoid hemorrhage (SAH). The endovascular perforation SAH model in Sprague-Dawley rats was used to study the effect of intranasal VitD3 (30 ng/kg) before (Pre-SAH + VitD3) and after (Post-SAH + VitD3) subarachnoid hemorrhage. Vitamin D3 (30, 60, 120 ng/kg/day) increased more than one fold endogenous OPN expression in astrocytes and endothelial cells of rat brain. Vitamin D3 significantly decreased brain edema and Evans blue extravasation. In addition, neurobehavioral scores were significantly higher in Pre-SAH + VitD3, but partly higher in Post-SAH + VitD3, group compared with SAH group. These protective effects of vitamin D3 were completely attenuated by intracerebroventricular injection of transcription inhibitor Actinomycin D and significantly inhibited by small interfering ribonucleic acid (siRNA) for vitamin D receptor and OPN in Pre-SAH + VitD3 rats. OPN expression was significantly higher in Pre-SAH + VitD3 rats, specifically A and C, but not B, isomers were upregulated in the astrocytes, leading to CD44 splicing, and P-gp glycosylation in brain endothelial cells. The results show that intranasal vitamin D3 attenuates blood-brain barrier (BBB) disruption through endogenous upregulation of OPN and subsequent CD44 and P-gp glycosylation signals in brain endothelial cells. Furthermore, this study identifies a novel strategy for the cost-effective management of subarachnoid hemorrhage.

  13. Focal CA3 hippocampal subfield atrophy following LGI1 VGKC-complex antibody limbic encephalitis

    OpenAIRE

    Miller, T; Chong, T; Aimola Davies, A; Ng, T; Johnson, M; Irani, S; Vincent, A; Husain, M; Jacob, S; Maddison, P; Kennard, C; Gowland, P; Rosenthal, C

    2017-01-01

    Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0....

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

    OpenAIRE

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

    2000-01-01

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

  15. Hydrogen-Rich Saline Attenuates Brain Injury Induced by Cardiopulmonary Bypass and Inhibits Microvascular Endothelial Cell Apoptosis Via the PI3K/Akt/GSK3β Signaling Pathway in Rats

    Directory of Open Access Journals (Sweden)

    Keyan Chen

    2017-10-01

    Full Text Available Background/Aims: Cardiopulmonary bypass (CPB is prone to inducing brain injury during open heart surgery. A hydrogen-rich solution (HRS can prevent oxidation and apoptosis, and inhibit inflammation. This study investigated effects of HRS on brain injury induced by CPB and regulatory mechanisms of the PI3K/Akt/GSK3β signaling pathway. Methods: A rat CPB model and an in vitro cell hypoxia model were established. After HRS treatment, Rat behavior was measured using neurological deficit score; Evans blue (EB was used to assess permeability of the blood-brain barrier (BBB; HE staining was used to observe pathological changes; Inflammatory factors and brain injury markers were detected by ELISA; the PI3K/Akt/GSK3β pathway-related proteins and apoptosis were assessed by western blot, immunohistochemistry and qRT –PCR analyses of brain tissue and neurons. Results: After CPB, brain tissue anatomy was disordered, and cell structure was abnormal. Brain tissue EB content increased. There was an increase in the number of apoptotic cells, an increase in expression of Bax and caspase-3, a decrease in expression of Bcl2, and increases in levels of Akt, GSK3β, P-Akt, and P-GSK3β in brain tissue. HRS treatment attenuated the inflammatory reaction ,brain tissue EB content was significantly reduced and significantly decreased expression levels of Bax, caspase-3, Akt, GSK3β, P-Akt, and P-GSK3β in the brain. After adding the PI3K signaling pathway inhibitor, LY294002, to rat cerebral microvascular endothelial cells (CMECs, HRS could reduce activated Akt expression and downstream regulatory gene phosphorylation of GSK3β expression, and inhibit CMEC apoptosis. Conclusion: The PI3K/Akt/GSK3β signaling pathway plays an important role in the mechanism of CPB-induced brain injury. HRS can reduce CPB-induced brain injury and inhibit CMEC apoptosis through the PI3K/Akt/GSK3β signaling pathway.

  16. Attenuated frontal and sensory inputs to the basal ganglia in cannabis users.

    Science.gov (United States)

    Blanco-Hinojo, Laura; Pujol, Jesus; Harrison, Ben J; Macià, Dídac; Batalla, Albert; Nogué, Santiago; Torrens, Marta; Farré, Magí; Deus, Joan; Martín-Santos, Rocío

    2017-07-01

    Heavy cannabis use is associated with reduced motivation. The basal ganglia, central in the motivation system, have the brain's highest cannabinoid receptor density. The frontal lobe is functionally coupled to the basal ganglia via segregated frontal-subcortical circuits conveying information from internal, self-generated activity. The basal ganglia, however, receive additional influence from the sensory system to further modulate purposeful behaviors according to the context. We postulated that cannabis use would impact functional connectivity between the basal ganglia and both internal (frontal cortex) and external (sensory cortices) sources of influence. Resting-state functional connectivity was measured in 28 chronic cannabis users and 29 controls. Selected behavioral tests included reaction time, verbal fluency and exposition to affective pictures. Assessments were repeated after one month of abstinence. Cannabis exposure was associated with (1) attenuation of the positive correlation between the striatum and areas pertaining to the 'limbic' frontal-basal ganglia circuit, and (2) attenuation of the negative correlation between the striatum and the fusiform gyrus, which is critical in recognizing significant visual features. Connectivity alterations were associated with lower arousal in response to affective pictures. Functional connectivity changes had a tendency to normalize after abstinence. The results overall indicate that frontal and sensory inputs to the basal ganglia are attenuated after chronic exposure to cannabis. This effect is consistent with the common behavioral consequences of chronic cannabis use concerning diminished responsiveness to both internal and external motivation signals. Such an impairment of the fine-tuning in the motivation system notably reverts after abstinence. © 2016 Society for the Study of Addiction.

  17. Differences in prefrontal, limbic, and white matter lesion volumes according to cognitive status in elderly patients with first-onset subsyndromal depression.

    Directory of Open Access Journals (Sweden)

    Jun-Young Lee

    Full Text Available The purpose of this preliminary study was to test the hypothesis that subsyndromal depression is associated with the volume of medial prefrontal regional gray matter and that of white matter lesions (WMLs in the brains of cognitively normal older people. We also explored the relationships between subsyndromal depression and medial prefrontal regional gray matter volume, limbic regional gray matter volume, and lobar WMLs in the brains of patients with mild cognitive impairment (MCI and Alzheimer's disease (AD. We performed a cross-sectional study comparing patients with subsyndromal depression and nondepressed controls with normal cognition (n = 59, MCI (n = 27, and AD (n = 27, adjusting for sex, age, years of education, and results of the Mini-Mental State Examination. Frontal WML volume was greater, and right medial orbitofrontal cortical volume was smaller in cognitively normal participants with subsyndromal depression than in those without subsyndromal depression. No volume differences were observed in medial prefrontal, limbic, or WML volumes according to the presence of subsyndromal depression in cognitively impaired patients. The absence of these changes in patients with MCI and AD suggests that brain changes associated with AD pathology may override the changes associated with subsyndromal depression.

  18. Measured attenuation correction methods

    International Nuclear Information System (INIS)

    Ostertag, H.; Kuebler, W.K.; Doll, J.; Lorenz, W.J.

    1989-01-01

    Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4-5 in brain studies to 50-100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide 68 Ge/ 68 Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: Transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible. (orig.)

  19. PET/MRI for Oncologic Brain Imaging: A Comparison of Standard MR-Based Attenuation Corrections with a Model-Based Approach for the Siemens mMR PET/MR System.

    Science.gov (United States)

    Rausch, Ivo; Rischka, Lucas; Ladefoged, Claes N; Furtner, Julia; Fenchel, Matthias; Hahn, Andreas; Lanzenberger, Rupert; Mayerhoefer, Marius E; Traub-Weidinger, Tatjana; Beyer, Thomas

    2017-09-01

    The aim of this study was to compare attenuation-correction (AC) approaches for PET/MRI in clinical neurooncology. Methods: Forty-nine PET/MRI brain scans were included: brain tumor studies using 18 F-fluoro-ethyl-tyrosine ( 18 F-FET) ( n = 31) and 68 Ga-DOTANOC ( n = 7) and studies of healthy subjects using 18 F-FDG ( n = 11). For each subject, MR-based AC maps (MR-AC) were acquired using the standard DIXON- and ultrashort echo time (UTE)-based approaches. A third MR-AC was calculated using a model-based, postprocessing approach to account for bone attenuation values (BD, noncommercial prototype software by Siemens Healthcare). As a reference, AC maps were derived from patient-specific CT images (CTref). PET data were reconstructed using standard settings after AC with all 4 AC methods. We report changes in diagnosis for all brain tumor patients and the following relative differences values (RDs [%]), with regards to AC-CTref: for 18 F-FET (A)-SUVs as well as volumes of interest (VOIs) defined by a 70% threshold of all segmented lesions and lesion-to-background ratios; for 68 Ga-DOTANOC (B)-SUVs as well as VOIs defined by a 50% threshold for all lesions and the pituitary gland; and for 18 F-FDG (C)-RD of SUVs of the whole brain and 10 anatomic regions segmented on MR images. Results: For brain tumor imaging (A and B), the standard PET-based diagnosis was not affected by any of the 3 MR-AC methods. For A, the average RDs of SUV mean were -10%, -4%, and -3% and of the VOIs 1%, 2%, and 7% for DIXON, UTE, and BD, respectively. Lesion-to-background ratios for all MR-AC methods were similar to that of CTref. For B, average RDs of SUV mean were -11%, -11%, and -3% and of the VOIs 1%, -4%, and -3%, respectively. In the case of 18 F-FDG PET/MRI (C), RDs for the whole brain were -11%, -8%, and -5% for DIXON, UTE, and BD, respectively. Conclusion: The diagnostic reading of PET/MR patients with brain tumors did not change with the chosen AC method. Quantitative accuracy of

  20. Prefrontal-limbic Functional Connectivity during Acquisition and Extinction of Conditioned Fear.

    Science.gov (United States)

    Barrett, Douglas W; Gonzalez-Lima, F

    2018-04-15

    This study is a new analysis to obtain novel metabolic data on the functional connectivity of prefrontal-limbic regions in Pavlovian fear acquisition and extinction of tone-footshock conditioning. Mice were analyzed with the fluorodeoxyglucose (FDG) autoradiographic method to metabolically map regional brain activity. New FDG data were sampled from the nuclei of the habenula and other regions implicated in aversive conditioning, such as infralimbic cortex, amygdala and periaqueductal gray regions. The activity patterns among these regions were inter-correlated during acquisition, extinction or pseudorandom training to develop a functional connectivity model. Two subdivisions of the habenular complex showed increased activity after acquisition relative to extinction, with the pseudorandom group intermediate between the other two groups. Significant acquisition activation effects were also found in centromedial amygdala, dorsomedial and ventrolateral periaqueductal gray. FDG uptake increases during extinction were found only in dorsal and ventral infralimbic cortex. The overall pattern of activity correlations between these regions revealed extensive but differential functional connectivity during acquisition and extinction training, with less functional connectivity found after pseudorandom training. Interestingly, habenula nuclei showed a distinct pattern of inter-correlations with amygdala nuclei during extinction. The functional connectivity model revealed changing interactions among infralimbic cortex, amygdala, habenula and periaqueductal gray regions through the stages of Pavlovian fear acquisition and extinction. This study provided new data on the contributions of the habenula to fear conditioning, and revealed previously unreported infralimbic-amygdala-habenula-periaqueductal gray interactions implicated in acquisition and extinction of conditioned fear. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Limbic justice--amygdala involvement in immediate rejection in the Ultimatum Game.

    Directory of Open Access Journals (Sweden)

    Katarina Gospic

    2011-05-01

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

  2. Psychotherapy, consciousness, and brain plasticity

    Directory of Open Access Journals (Sweden)

    Daniel eCollerton

    2013-09-01

    Full Text Available Purely psychological treatments for emotional distress produce lasting, measureable, and reproducible changes in cognitive and emotional consciousness and brain function. How these changes come about illustrates the interplay between brain and consciousness. Studies of the effects of psychotherapy highlight the holistic nature of consciousness. Pre and post treatment functional Magnetic Resonance Imaging localises the brain changes following psychotherapy to frontal, cingulate, and limbic circuits, but emphasise that these areas support a wide range of conscious experiences. Multivoxel Pattern Analysis of distributed changes in function across these brain areas may be able to provide the ability to distinguish between different states of consciousness.

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

    Directory of Open Access Journals (Sweden)

    Chiara Cerami

    Full Text Available 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.

  4. Cathinone, an active principle of Catha edulis, accelerates oxidative stress in the limbic area of swiss albino mice.

    Science.gov (United States)

    Safhi, Mohammed M; Alam, Mohammad Firoz; Hussain, Sohail; Hakeem Siddiqui, Mohammed Abdul; Khuwaja, Gulrana; Jubran Khardali, Ibrahim Abdu; Al-Sanosi, Rashad Mohammed; Islam, Fakhrul

    2014-10-28

    Cathinone hydrochloride is an active principle of the khat plant (Catha edulis) that produces pleasurable and stimulating effects in khat chewers. To the best of our knowledge no data of cathinone on oxidative stress in limbic areas of mice is available. This is the first study of cathinone on oxidative stress in limbic areas of the brain in Swiss albino male mice. The animals were divided into four groups. Group-I was the control group and received vehicle, while groups-II to IV received (-)-cathinone hydrochloride (0.125, 0.25 and 0.5 mg/kg body wt., i.p.) once daily for 15 days. The level of lipid peroxidation (LPO) was elevated dose-dependently and was significant (p<0.05, p<0.01) with doses of 0.25 and 0.5mg/kg body wt. of cathinone as compared to control group. In contrast, the content of reduced glutathione (GSH) was decreased significantly (p<0.01, p<0.001) with doses of 0.25 and 0.5mg/kg body wt. of cathinone as compared to control group. The activity of antioxidant enzymes (GPx, GR, GST, CAT, and SOD) was also decreased dose-dependently: the decreased activity of GPx, GR, catalase and SOD was significant with doses of 0.25 and 0.5 mg of cathinone as compared to control group, while the activity of GST was decreased dose-dependently and was significant with 0.5mg of cathinone as compared to control group. The results indicate that the cathinone generated oxidative stress hampered antioxidant enzymes, glutathione and lipid peroxidation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. An SPM8-Based Approach for Attenuation Correction Combining Segmentation and Nonrigid Template Formation: Application to Simultaneous PET/MR Brain Imaging

    DEFF Research Database (Denmark)

    Izquierdo-Garcia, David; Hansen, Adam E; Förster, Stefan

    2014-01-01

    coregistered using a diffeomorphic approach. A similar procedure was used to coregister the anatomic MR data for a new subject to the template. Finally, the CT-like images obtained by applying the inverse transformations were converted to linear attenuation coefficients to be used for AC of PET data...

  6. The Limbic System Conception and Its Historical Evolution

    Directory of Open Access Journals (Sweden)

    Marcelo R. Roxo

    2011-01-01

    Full Text Available 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.

  7. Sumoylation of IkB attenuates NF-kB-induced nitrosative stress at rostral ventrolateral medulla and cardiovascular depression in experimental brain death.

    Science.gov (United States)

    Tsai, Ching-Yi; Li, Faith C H; Wu, Carol H Y; Chang, Alice Y W; Chan, Samuel H H

    2016-09-22

    Small ubiquitin-related modifier (SUMO) is a group of proteins that participates in post-translational modifications. One known SUMO target is the transcription factor nuclear factor-kB (NF-kB) that plays a pivotal role in many disease processes; sumoylation inactivates NF-kB by conjugation with inhibitors of NF-kB (IkB). Our laboratory demonstrated previously that transcriptional upregulation of nitric oxide synthase II (NOS II) by NF-kB, leading to nitrosative stress by the formation of peroxynitrite in the rostral ventrolateral medulla (RVLM), underpins the defunct brain stem cardiovascular regulation that precedes brain death. Based on an experimental endotoxemia model, this study evaluated the hypothesis that sumoylation plays a pro-life role in brain death by interacting with the NF-kB/NOS II/peroxynitrite signaling pathway in the RVLM. In Sprague-Dawley rats, intravenous administration of Escherichia coli lipopolysaccharide (LPS; 10 mg kg -1 ) elicited an augmentation of SUMO-1 and ubiquitin-conjugase 9 (Ubc9) mRNA or protein levels, alongside SUMO-1-conjugated proteins in the RVLM. Immunoneutralization of SUMO-1 or Ubc9 in the RVLM significantly potentiated the already diminished sumoylation of IkBα and intensified NF-kB activation and NOS II/peroxynitrite expression in this brain stem substrate, together with exacerbated fatality, cardiovascular depression and reduction of an experimental index of a life-and-death signal detected from arterial pressure that disappears in comatose patients signifying failure of brain stem cardiovascular regulation before brain death. We conclude that sumoylation of IkB in the RVLM ameliorates the defunct brain stem cardiovascular regulation that underpins brain death in our experimental endotoxemia modal by reducing nitrosative stress via inhibition of IkB degradation that diminishes the induction of the NF-kB/NOS II/peroxynitrite signaling cascade.

  8. [Attenuation of inhibitory influence of hormones on adenylyl cyclase systems in the myocardium and brain of rats with obesity and type 2 diabetes mellitus and effect of intranasal insulin on it].

    Science.gov (United States)

    Kuznetsova, L A; Plesneva, S A; Sharova, T S; Pertseva, M N; Shpakov, A O

    2014-01-01

    The functional state of the adenylyl cyclase signaling system (ACSS) and its regulation by hormones, the inhibitors of adenylyl cyclase (AC)--somatostatin (SST) in the brain and myocardium and 5-nonyloxytryptamine (5-NOT) in the brain of rats of different ages (5- and 7-month-old) with experimental obesity and a combination of obesity and type 2 diabetes mellitus (DM2), and the effect of long-term treatment of animals with intranasally administered insulin (II) on ACSS were studied. It was shown that the basal AC activity in rats with obesity and DM2 was increased in the myocardium, and to the lesser extent in the brain, the treatment with II reducing this parameter. The AC stimulating effects of forskolin are decreased in the myocardium, but not in the brain, of rats with obesity and DM2. The treatment with II restored the AC action of forskolin in the 7-month-old animals, but has little effect on it in the 5-month-old rats. In obesity the basal AC activity and its stimulation by forskolin varied insignificantly and weakly changed in treatment of animals with II. The AC inhibitory effects of SST and 5-NOT in the investigated pathology are essentially attenuated, the effect of SST to the greatest extent, which we believe to be associated with a reduction in the functional activity of Gi-proteins. The II treatment of animals with obesity and with a combination of obesity and DM2 restored completely or partially the AC inhibiting effects of hormones, to the greatest extent in the brain. Since impaired functioning of ACSS is one of the causes of the metabolic syndrome and DM2, their elimination by treatments with II can be an effective approach to treat these diseases and their CNS and cardiovascular system complications.

  9. A novel neuron-enriched protein SDIM1 is down regulated in Alzheimer's brains and attenuates cell death induced by DNAJB4 over-expression in neuro-progenitor cells

    Directory of Open Access Journals (Sweden)

    Lei Joy X

    2011-01-01

    Full Text Available Abstract Background Molecular changes in multiple biological processes contribute to the development of chronic neurodegeneration such as late onset Alzheimer's disease (LOAD. To discover how these changes are reflected at the level of gene expression, we used a subtractive transcription-based amplification of mRNA procedure to identify novel genes that have altered expression levels in the brains of Alzheimer's disease (AD patients. Among the genes altered in expression level in AD brains was a transcript encoding a novel protein, SDIM1, that contains 146 amino acids, including a typical signal peptide and two transmembrane domains. Here we examined its biochemical properties and putative roles in neuroprotection/neurodegeneration. Results QRT-PCR analysis of additional AD and control post-mortem human brains showed that the SDIM1 transcript was indeed significantly down regulated in all AD brains. SDIM1 is more abundant in NT2 neurons than astrocytes and present throughout the cytoplasm and neural processes, but not in the nuclei. In NT2 neurons, it is highly responsive to stress conditions mimicking insults that may cause neurodegeneration in AD brains. For example, SDIM1 was significantly down regulated 2 h after oxygen-glucose deprivation (OGD, though had recovered 16 h later, and also appeared significantly up regulated compared to untreated NT2 neurons. Overexpression of SDIM1 in neuro-progenitor cells improved cells' ability to survive after injurious insults and its downregulation accelerated cell death induced by OGD. Yeast two-hybrid screening and co-immunoprecipitation approaches revealed, both in vitro and in vivo, an interaction between SDIM1 and DNAJB4, a heat shock protein hsp40 homolog, recently known as an enhancer of apoptosis that also interacts with the mu opioid receptor in human brain. Overexpression of DNAJB4 alone significantly reduced cell viability and SDIM1 co-overexpression was capable of attenuating the cell death

  10. Limbic system perfusion in Alzheimer's disease measured by MRI-coregistered HMPAO SPET

    International Nuclear Information System (INIS)

    Callen, David J.A.; Black, Sandra E.; Caldwell, Curtis B.

    2002-01-01

    The goal of this study was to perform a systematic, semi-quantitative analysis of limbic perfusion in patients with Alzheimer's disease (AD) using coregistered single-photon emission tomography (SPET) images aligned to magnetic resonance (MR) images. Limbic perfusion in 40 patients with mild to moderate AD was compared with that of 17 age-, sex-, and education-matched normal controls (NC). HMPAO SPET scans and 3D T1-weighted MR images were acquired for each subject. Structures of the limbic system (i.e. hippocampus, amygdala, anterior thalamus, hypothalamus, mamillary bodies, basal forebrain, septal area and cingulate, orbitofrontal and parahippocampal cortices) were traced on the MR images and transferred to the coregistered SPET scans. Perfusion ratios for all limbic regions were calculated relative to cerebellar perfusion. General linear model multivariate analysis revealed that, overall, limbic structures showed significant hypoperfusion (F=7.802, P 2 =0.695) in AD patients compared with NC. Greatest differences (d≥0.8) were found in the hippocampus, as well as all areas of the cingulate cortex. Significant relative hypoperfusion was also apparent in the parahippocampal cortex, amygdala/entorhinal cortex, septal area and anterior thalamus, all of which showed medium to large effect sizes (d=0.6-0.8). No significant relative perfusion differences were detected in the basal forebrain, hypothalamus, mamillary bodies or orbitofrontal cortex. Logistic regression indicated that posterior cingulate cortex perfusion was able to discriminate AD patients from NC with 93% accuracy (95% sensitivity, 88% specificity). The current results suggest that most, but not all, limbic structures show significant relative hypoperfusion in AD. These findings validate previous post-mortem studies and could be useful in improving diagnostic accuracy, monitoring disease progression and evaluating potential treatment strategies in AD. (orig.)

  11. Limbic system perfusion in Alzheimer's disease measured by MRI-coregistered HMPAO SPET

    Energy Technology Data Exchange (ETDEWEB)

    Callen, David J.A. [Institute of Medical Science, Research Program in Aging, Imaging, Sunnybrook and Women' s University of Toronto, ON (Canada); Black, Sandra E. [Cognitive Neurology Unit and Research Program in Aging, Sunnybrook and Women' s College Health Sciences Centre, Toronto, ON (Canada); Institute of Medical Science, Research Program in Aging, Imaging, Sunnybrook and Women' s University of Toronto, ON (Canada); Department of Medicine (Neurology), University of Toronto, ON (Canada); Caldwell, Curtis B. [Department of Medical Imaging, Sunnybrook and Women' s College Health Sciences Centre and University of Toronto, CN (Canada)

    2002-07-01

    The goal of this study was to perform a systematic, semi-quantitative analysis of limbic perfusion in patients with Alzheimer's disease (AD) using coregistered single-photon emission tomography (SPET) images aligned to magnetic resonance (MR) images. Limbic perfusion in 40 patients with mild to moderate AD was compared with that of 17 age-, sex-, and education-matched normal controls (NC). HMPAO SPET scans and 3D T1-weighted MR images were acquired for each subject. Structures of the limbic system (i.e. hippocampus, amygdala, anterior thalamus, hypothalamus, mamillary bodies, basal forebrain, septal area and cingulate, orbitofrontal and parahippocampal cortices) were traced on the MR images and transferred to the coregistered SPET scans. Perfusion ratios for all limbic regions were calculated relative to cerebellar perfusion. General linear model multivariate analysis revealed that, overall, limbic structures showed significant hypoperfusion (F=7.802, P<0.00001, {eta}{sup 2}=0.695) in AD patients compared with NC. Greatest differences (d{>=}0.8) were found in the hippocampus, as well as all areas of the cingulate cortex. Significant relative hypoperfusion was also apparent in the parahippocampal cortex, amygdala/entorhinal cortex, septal area and anterior thalamus, all of which showed medium to large effect sizes (d=0.6-0.8). No significant relative perfusion differences were detected in the basal forebrain, hypothalamus, mamillary bodies or orbitofrontal cortex. Logistic regression indicated that posterior cingulate cortex perfusion was able to discriminate AD patients from NC with 93% accuracy (95% sensitivity, 88% specificity). The current results suggest that most, but not all, limbic structures show significant relative hypoperfusion in AD. These findings validate previous post-mortem studies and could be useful in improving diagnostic accuracy, monitoring disease progression and evaluating potential treatment strategies in AD. (orig.)

  12. Personalized mapping of the deep brain with a white matter attenuated inversion recovery (WAIR) sequence at 1.5-tesla: Experience based on a series of 156 patients.

    Science.gov (United States)

    Zerroug, A; Gabrillargues, J; Coll, G; Vassal, F; Jean, B; Chabert, E; Claise, B; Khalil, T; Sakka, L; Feschet, F; Durif, F; Boyer, L; Coste, J; Lemaire, J-J

    2016-08-01

    Deep brain mapping has been proposed for direct targeting in stereotactic functional surgery, aiming to personalize electrode implantation according to individual MRI anatomy without atlas or statistical template. We report our clinical experience of direct targeting in a series of 156 patients operated on using a dedicated Inversion Recovery Turbo Spin Echo sequence at 1.5-tesla, called White Matter Attenuated Inversion Recovery (WAIR). After manual contouring of all pertinent structures and 3D planning of trajectories, 312 DBS electrodes were implanted. Detailed anatomy of close neighbouring structures, whether gray nuclei or white matter regions, was identified during each planning procedure. We gathered the experience of these 312 deep brain mappings and elaborated consistent procedures of anatomical MRI mapping for pallidal, subthalamic and ventral thalamic regions. We studied the number of times the central track anatomically optimized was selected for implantation of definitive electrodes. WAIR sequence provided high-quality images of most common functional targets, successfully used for pure direct stereotactic targeting: the central track corresponding to the optimized primary anatomical trajectory was chosen for implantation of definitive electrodes in 90.38%. WAIR sequence is anatomically reliable, enabling precise deep brain mapping and direct stereotactic targeting under routine clinical conditions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

    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. Oxytocin attenuates trust as a subset of more general reinforcement learning, with altered reward circuit functional connectivity in males.

    Science.gov (United States)

    Ide, Jaime S; Nedic, Sanja; Wong, Kin F; Strey, Shmuel L; Lawson, Elizabeth A; Dickerson, Bradford C; Wald, Lawrence L; La Camera, Giancarlo; Mujica-Parodi, Lilianne R

    2018-07-01

    Oxytocin (OT) is an endogenous neuropeptide that, while originally thought to promote trust, has more recently been found to be context-dependent. Here we extend experimental paradigms previously restricted to de novo decision-to-trust, to a more realistic environment in which social relationships evolve in response to iterative feedback over twenty interactions. In a randomized, double blind, placebo-controlled within-subject/crossover experiment of human adult males, we investigated the effects of a single dose of intranasal OT (40 IU) on Bayesian expectation updating and reinforcement learning within a social context, with associated brain circuit dynamics. Subjects participated in a neuroeconomic task (Iterative Trust Game) designed to probe iterative social learning while their brains were scanned using ultra-high field (7T) fMRI. We modeled each subject's behavior using Bayesian updating of belief-states ("willingness to trust") as well as canonical measures of reinforcement learning (learning rate, inverse temperature). Behavioral trajectories were then used as regressors within fMRI activation and connectivity analyses to identify corresponding brain network functionality affected by OT. Behaviorally, OT reduced feedback learning, without bias with respect to positive versus negative reward. Neurobiologically, reduced learning under OT was associated with muted communication between three key nodes within the reward circuit: the orbitofrontal cortex, amygdala, and lateral (limbic) habenula. Our data suggest that OT, rather than inspiring feelings of generosity, instead attenuates the brain's encoding of prediction error and therefore its ability to modulate pre-existing beliefs. This effect may underlie OT's putative role in promoting what has typically been reported as 'unjustified trust' in the face of information that suggests likely betrayal, while also resolving apparent contradictions with regard to OT's context-dependent behavioral effects. Copyright

  15. Hyperbaric oxygen therapy or hydroxycobalamin attenuates surges in brain interstitial lactate and glucose; and hyperbaric oxygen improves respiratory status in cyanide-intoxicated rats

    DEFF Research Database (Denmark)

    Lawson-Smith, P; Olsen, Niels Vidiendal; Hyldegaard, O

    2011-01-01

    Cyanide (CN) intoxication inhibits cellular oxidative metabolism and may result in brain damage. Hydroxycobalamin (OHCob) is one among other antidotes that may be used following intoxication with CN. Hyperbaric oxygen (HBO2) is recommended when supportive measures or antidotes fail. However...

  16. Milk Fat Globule-Epidermal Growth Factor-8 Pretreatment Attenuates Apoptosis and Inflammation via the Integrin-β3 Pathway after Surgical Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Yicai Xiao

    2018-02-01

    Full Text Available Iatrogenic brain injury inevitably occurs in neurosurgical operations, leading to brain edema, ischemia, intracranial hematoma, and other postoperative complications, eventually worsening neurological outcomes of patients. If apoptotic cells are not rapidly eliminated by phagocytic engulfment, they may communicate with surrounding cells to undergo secondary necrosis and releasing toxic signals. Recent studies have shown that milk fat globule-epidermal growth factor-8 (MFGE8, which promotes phagocytosis and inhibits inflammation, is an endogenous protective factor in response to brain infarction, Alzheimer’s disease, subarachnoid hemorrhage, and prion disease. In the present study, we sought to investigate the different effects of both pretreated and posttreated recombinant milk fat globule-epidermal growth factor-8 (rhMFGE8 for the surgical brain injury (SBI rat model and potential involvement of its receptor integrin β3 for apoptosis and neuroinflammation after SBI. One hundred and sixty-seven male rats were employed in the preset study. Experiment 1 was performed to evaluate neurological scores and MFGE8, cleaved caspase-3 (CC3, and interleukine-1 beta (IL-1β levels at 3, 24, and 120 h after SBI. Experiment 2 was performed to evaluate the effects of rhMFGE8 pretreatment (10 min before SBI and rhMFGE8 posttreatment (6 h after SBI on brain edema at 24 and 72 h after SBI. Experiment 3 was performed to evaluate the potential anti-apoptotic and anti-inflammatory effects of rhMFGE8 pretreatment and posttreatment. Experiment 4 sought to investigate the involvement of the integrin-β3 signal in the effects of MFGE8 pretreatment. Our data showed rhMFGE8 pretreatment alleviated neurological deficits and decreased brain water content and apoptotic cells in the SBI model, which exhibited neurological dysfunction, apoptosis, and inflammation. Meanwhile, MFGE8 siRNA, which inhibited endogenous MFGE8 expression, significantly increased IL-1

  17. Autoradiographic evidence for methamphetamine-induced striatal dopaminergic loss in mouse brain: attenuation in CuZn-superoxide dismutase transgenic mice.

    Science.gov (United States)

    Hirata, H; Ladenheim, B; Carlson, E; Epstein, C; Cadet, J L

    1996-04-01

    Methamphetamine (METH) has long-lasting neurotoxic effects on the nigrostriatal dopamine (DA) system of rodents. METH-induced neurotoxicity is thought to involve release of DA in presynaptic DA terminals, which is associated with increased formation of oxygen-based free radicals. We have recently shown that METH-induced striatal DA depletion is attenuated in transgenic (Tg) mice that express the human CuZn-superoxide dismutase (SOD) enzyme. That study did not specifically address the issue of loss of DA terminals. In the present study, we have used receptor autoradiographic studies of [(125)I]RTI-121-labeled DA uptake sites to evaluate the effects of several doses of METH on striatal DA terminals of Non-Tg as well as of heterozygous and homozygous SOD-Tg mice. In Non-Tg mice, METH caused decreases in striatal DA uptake sites in a dose-dependent fashion. The loss of DA terminals was more prominent in the lateral region than in the medial subdivisions of the striatum. In SOD-Tg mice, the loss of DA terminals caused by METH was attenuated in a gene dosage-dependent fashion, with the homozygous mice showing the greatest protection. Female mice were somewhat more resistant than male mice against these deleterious effects of METH. These results provide further evidence for a role of superoxide radicals in the long-term effects of METH. They also suggest the notion of a gender-specific handling of oxidative stress.

  18. SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats.

    Science.gov (United States)

    Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Kerdphoo, Sasiwan; Jaiwongkam, Thidarat; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2017-10-15

    Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n=8) or a high-fat diet (HFD, n=32) for 16weeks. At week 13, the HFD-fed rats were divided into four subgroups (n=8/subgroup) to receive either a vehicle, vildagliptin (3mg/kg/day) dapagliflozin (1mg/kg/day) or combined drugs for four weeks. ND rats were given a vehicle for four weeks. Metabolic parameters and brain function were investigated. The results demonstrated that HFD rats developed obese-insulin resistance and cognitive decline. Dapagliflozin had greater efficacy on improved peripheral insulin sensitivity and reduced weight gain than vildagliptin. Single therapy resulted in equally improved brain mitochondrial function, insulin signaling, apoptosis and prevented cognitive decline. However, only dapagliflozin improved hippocampal synaptic plasticity. A combination of the drugs had greater efficacy in improving brain insulin sensitivity and reducing brain oxidative stress than the single drug therapy. These findings suggested that dapagliflozin and vildagliptin equally prevented cognitive decline in the obese-insulin resistance, possibly through some similar mechanisms. Dapagliflozin had greater efficacy than vildagliptin for preserving synaptic plasticity, thus combined drugs could be the best therapeutic approach for neuroprotection in the obese-insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Baseline frontostriatal-limbic connectivity predicts reward-based memory formation.

    Science.gov (United States)

    Hamann, Janne M; Dayan, Eran; Hummel, Friedhelm C; Cohen, Leonardo G

    2014-12-01

    Reward mediates the acquisition and long-term retention of procedural skills in humans. Yet, learning under rewarded conditions is highly variable across individuals and the mechanisms that determine interindividual variability in rewarded learning are not known. We postulated that baseline functional connectivity in a large-scale frontostriatal-limbic network could predict subsequent interindividual variability in rewarded learning. Resting-state functional MRI was acquired in two groups of subjects (n = 30) who then trained on a visuomotor procedural learning task with or without reward feedback. We then tested whether baseline functional connectivity within the frontostriatal-limbic network predicted memory strength measured immediately, 24 h and 1 month after training in both groups. We found that connectivity in the frontostriatal-limbic network predicted interindividual variability in the rewarded but not in the unrewarded learning group. Prediction was strongest for long-term memory. Similar links between connectivity and reward-based memory were absent in two control networks, a fronto-parieto-temporal language network and the dorsal attention network. The results indicate that baseline functional connectivity within the frontostriatal-limbic network successfully predicts long-term retention of rewarded learning. © 2014 Wiley Periodicals, Inc.

  20. Pubertally born neurons and glia are functionally integrated into limbic and hypothalamic circuits of the male Syrian hamster.

    Science.gov (United States)

    Mohr, Margaret A; Sisk, Cheryl L

    2013-03-19

    During puberty, the brain goes through extensive remodeling, involving the addition of new neurons and glia to brain regions beyond the canonical neurogenic regions (i.e., dentate gyrus and olfactory bulb), including limbic and hypothalamic cell groups associated with sex-typical behavior. Whether these pubertally born cells become functionally integrated into neural circuits remains unknown. To address this question, we gave male Syrian hamsters daily injections of the cell birthdate marker bromodeoxyuridine throughout puberty (postnatal day 28-49). Half of the animals were housed in enriched environments with access to a running wheel to determine whether enrichment increased the survival of pubertally born cells compared with the control environment. At 4 wk after the last BrdU injection, animals were allowed to interact with a receptive female and were then killed 1 h later. Triple-label immunofluorescence for BrdU, the mature neuron marker neuronal nuclear antigen, and the astrocytic marker glial fibrillary acidic protein revealed that a proportion of pubertally born cells in the medial preoptic area, arcuate nucleus, and medial amygdala differentiate into either mature neurons or astrocytes. Double-label immunofluorescence for BrdU and the protein Fos revealed that a subset of pubertally born cells in these regions is activated during sociosexual behavior, indicative of their functional incorporation into neural circuits. Enrichment affected the survival and activation of pubertally born cells in a brain region-specific manner. These results demonstrate that pubertally born cells located outside of the traditional neurogenic regions differentiate into neurons and glia and become functionally incorporated into neural circuits that subserve sex-typical behaviors.

  1. Physical exercise prevents short and long-term deficits on aversive and recognition memory and attenuates brain oxidative damage induced by maternal deprivation.

    Science.gov (United States)

    Neves, Ben-Hur; Menezes, Jefferson; Souza, Mauren Assis; Mello-Carpes, Pâmela B

    2015-12-01

    It is known from previous research that physical exercise prevents long-term memory deficits induced by maternal deprivation in rats. But we could not assume similar effects of physical exercise on short-term memory, as short- and long-term memories are known to result from some different memory consolidation processes. Here we demonstrated that, in addition to long-term memory deficit, the short-term memory deficit resultant from maternal deprivation in object recognition and aversive memory tasks is also prevented by physical exercise. Additionally, one of the mechanisms by which the physical exercise influences the memory processes involves its effects attenuating the oxidative damage in the maternal deprived rats' hippocampus and prefrontal cortex.

  2. Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease.

    Science.gov (United States)

    Chao, Yin Xia; He, Bei Ping; Tay, Samuel Sam Wah

    2009-11-30

    Immunomodulatory effects of transplanted mesenchymal stem cells (MSCs) in the treatment of Parkinson's disease were studied in the MPTP-induced mouse model. MPTP treatment induced a significant loss of dopaminergic neurons, decreased expressions of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB). Our study further discovered that infiltration of MBLs into the brain to bind with microglia was detected in the SNc of MPTP-treated mice, suggesting that the BBB compromise and MBL infiltration might be involved in the pathogenesis of MPTP-induced PD. In addition, MPTP treatment also increased the expression of mannose-binding lectins (MBLs) in the liver tissue. Intravenous transplantation of MSCs into MPTP-treated mice led to recovery of BBB integrity, suppression of MBL infiltration at SNc and MBL expression in the liver, suppression of microglial activation and prevention of dopaminergic neuron death. No transplanted MSCs were observed to differentiate into dopaminergic neurons, while the MSCs migrated into the SNc and released TGF-beta1 there. Therefore, intravenous transplantation of MSCs which protect dopaminergic neurons from MPTP toxicity may be engaged in anyone or a combination of these mechanisms: repair of the BBB, reduction of MBL in the brain, inhibition of microglial cytotoxicity, and direct protection of dopaminergic neurons.

  3. Attenuation of Streptozotocin-Induced Lipid Profile Anomalies in the Heart, Brain, and mRNA Expression of HMG-CoA Reductase by Diosgenin in Rats.

    Science.gov (United States)

    Hao, Shuang; Xu, Rihao; Li, Dan; Zhu, Zhicheng; Wang, Tiance; Liu, Kexiang

    2015-07-01

    Diabetes mellitus is associated with significant morbidity and mortality that contributes to pathogenesis of cardiovascular diseases. Diosgenin, a naturally occurring aglycone, is present abundantly in fenugreek. The steroidal saponin is being used as a traditional medicine for diabetes. The present study has investigated the effects of diosgenin on lipid profile in the heart and brain, mRNA expression, and hepatic HMG-CoA reductase (HMGR) activity of streptozotocin-induced diabetic rats. In our study, diosgenin was administered (40 mg/kg b.w.) orally for 45 days to control animals and experimentally induced diabetic rats. The effects of diosgenin on glucose, plasma insulin, cholesterol, triglycerides, free fatty acids, and phospholipids (PLs) in the heart and brain were studied. The levels of glucose, cholesterol, triglycerides, free fatty acids, PLs, and HMGR activity were increased significantly (P rats. Administration of diosgenin to diabetic rats significantly reduced blood glucose, cholesterol, triglycerides, free fatty acids, PLs levels, and also HMGR activity. In addition, the plasma insulin level was increased in diosgenin-treated diabetic rats. The above findings were correlated with histological observations of the heart and brain. The results showed that administration of diosgenin remarkably increased plasma insulin level with absolute reduction of blood glucose, lipid profile, and HMGR level when compared to diabetic control rats. The results have suggested that diosgenin prevents hypercholesterolemia and hepatosteatosis by modulation of enzymatic expression that is associated with cholesterol metabolism.

  4. C1q/Tumor Necrosis Factor-related Protein-3 Attenuates Brain Injury after Intracerebral Hemorrhage via AMPK-dependent pathway in Rat

    Directory of Open Access Journals (Sweden)

    Shaohua Wang

    2016-10-01

    Full Text Available C1q/tumor necrosis factor-related protein-3 (CTRP3 is a recently discovered adiponectin paralog with established metabolic regulatory properties. However, the role of CTRP3 in intracerebral hemorrhage (ICH is still mostly unresolved. The aim of the present report was to explore the possible neuroprotective effect of CTRP3 in an ICH rat model and to elucidate the fundamental mechanisms. ICH was induced in rats by intracerebral infusion of autologous arterial blood. The effects of exogenous CTRP3 (recombinant or lentivirus CTRP3 on brain injury were explored on day 7. Treatment with CTRP3 reduced brain edema, protected against disruption of the blood-brain barrier, improved neurological functions, and promoted angiogenesis. Furthermore, CTRP3 greatly intensified phosphorylation of AMP-activated protein kinase (AMPK in addition to expression of hypoxia inducing factor-1α (HIF-1α and vascular endothelial growth factor (VEGF. Finally, the protective effects of CTRP3 could be blocked by either AMPK or VEGF inhibitors. Our findings give the first evidence that CTRP3 is a new proangiogenic and neuroprotective adipokine, which may exert its protective effects at least partly through an AMPK/HIF-1α/ VEGF-dependent pathway, and suggest that CTRP3 may provide a new therapeutic strategy for ICH.

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

    International Nuclear Information System (INIS)

    Fujimoto, So; Yamaguchi, Yasuhiro; Gotanda, Hiroshi

    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 electroencephalogram (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 fluorodeoxyglucose (FDG)-positron emission tomography (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 3rd and 4th 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. (author)

  6. Architectural Representation of Valence in the Limbic System

    Science.gov (United States)

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

    2016-01-01

    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

  7. Knockdown of long noncoding antisense RNA brain-derived neurotrophic factor attenuates hypoxia/reoxygenation-induced nerve cell apoptosis through the BDNF-TrkB-PI3K/Akt signaling pathway.

    Science.gov (United States)

    Zhong, Jian-Bin; Li, Xie; Zhong, Si-Ming; Liu, Jiu-Di; Chen, Chi-Bang; Wu, Xiao-Yan

    2017-09-27

    Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal cell apoptosis. The antisense RNA of brain-derived neurotrophic factor (BDNF-AS) is a natural antisense transcript that is transcribed opposite the gene that encodes BDNF. The aim of this study was to determine whether knockdown of BDNF-AS can suppress hypoxia/reoxygenation (H/R)-induced neuronal cell apoptosis and whether this is mediated by the BDNF-TrkB-PI3K/Akt pathway. We detected the expression of BDNF and BDNF-AS in brain tissue from 20 patients with cerebral infarction and five patients with other diseases (but no cerebral ischemia). We found that BDNF expression was significantly downregulated in patients with cerebral infarction, whereas the expression of BDNF-AS was significantly upregulated. In both human cortical neurons (HCN2) and human astrocytes, H/R significantly induced the expression of BDNF-AS, but significantly decreased BDNF expression. H/R also significantly induced apoptosis and reduced the mitochondrial membrane potential in these cells. Following downregulation of BDNF-AS by siRNA in human cortical neurons and human astrocyte cells, BDNF expression was significantly upregulated and the H/R-induced upregulation of BDNF-AS was significantly attenuated. BDNF-AS siRNA inhibited H/R-induced cell apoptosis and ameliorated the H/R-induced suppression of mitochondrial membrane potential. H/R inhibited the expression of BDNF, p-AKT/AKT, and TrKB, and this inhibition was recovered by BDNF-AS siRNA. In summary, this study indicates that BDNF-AS siRNA induces activation of the BDNF-TrkB-PI3K/Akt pathway following H/R-induced neurotoxicity. These findings will be useful toward the application of BDNF-AS siRNA for the treatment of neurodegenerative diseases.

  8. Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression.

    Science.gov (United States)

    Xiang, Wei; Tian, Canhui; Peng, Shunli; Zhou, Liang; Pan, Suyue; Deng, Zhen

    2017-11-04

    The let-7 family of microRNAs (miRNAs) plays an important role on endothelial cell function. However, there have been few studies on their role under ischemic conditions. In this study, we demonstrate that let-7i, belonging to the let-7 family, rescues human brain microvascular endothelial cells (HBMECs) in an oxygen-glucose deprivation (OGD) model. Our data show that the expression of let-7 family miRNAs was downregulated after OGD. Overexpression of let-7i significantly alleviated cell death and improved survival of OGD-treated HBMECs. Let-7i also protected permeability in an in vitro blood brain barrier (BBB) model. Further, let-7i downregulated the expression of toll-like receptor 4 (TLR4), an inflammation trigger. Moreover, overexpression of let-7i decreased matrix metallopeptidase 9 (MMP9) and inducible nitric oxide synthase (iNOS) expression under OGD. Upon silencing TLR4 expression in HBMECs, the anti-inflammatory effect of let-7i was abolished. Our research suggests that let-7i promotes OGD-induced inflammation via downregulating TLR4 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. ESCRT-mediated uptake and degradation of brain-targeted α-synuclein single chain antibody attenuates neuronal degeneration in vivo.

    Science.gov (United States)

    Spencer, Brian; Emadi, Sharareh; Desplats, Paula; Eleuteri, Simona; Michael, Sarah; Kosberg, Kori; Shen, Jay; Rockenstein, Edward; Patrick, Christina; Adame, Anthony; Gonzalez, Tania; Sierks, Michael; Masliah, Eliezer

    2014-10-01

    Parkinson's disease and dementia with Lewy bodies are neurodegenerative disorders characterized by accumulation of α-synuclein (α-syn). Recently, single-chain fragment variables (scFVs) have been developed against individual conformational species of α-syn. Unlike more traditional monoclonal antibodies, these scFVs will not activate or be endocytosed by Fc receptors. For this study, we investigated an scFV directed against oligomeric α-syn fused to the LDL receptor-binding domain from apolipoprotein B (apoB). The modified scFV showed enhanced brain penetration and was imported into neuronal cells through the endosomal sorting complex required for transport (ESCRT) pathway, leading to lysosomal degradation of α-syn aggregates. Further analysis showed that the scFV was effective at ameliorating neurodegenerative pathology and behavioral deficits observed in the mouse model of dementia with Lewy bodies/Parkinson's disease. Thus, the apoB modification had the effect of both increasing accumulation of the scFV in the brain and directing scFV/α-syn complexes for degradation through the ESCRT pathway, leading to improved therapeutic potential of immunotherapy.

  10. Anticonvulsant effects of gamma surgery in a model of chronic spontaneous limbic epilepsy in rats.

    Science.gov (United States)

    Chen, Z F; Kamiryo, T; Henson, S L; Yamamoto, H; Bertram, E H; Schottler, F; Patel, F; Steiner, L; Prasad, D; Kassell, N F; Shareghis, S; Lee, K S

    2001-02-01

    The management of intractable epilepsy remains a challenge, despite advances in its surgical and nonsurgical treatment. The identification of low-risk, low-cost therapeutic strategies that lead to improved outcome is therefore an important ongoing goal of basic and clinical research. Single-dose focal ionizing beam radiation delivered at necrosis-inducing and subnecrotic levels was investigated for its effects on seizure activity by using an established model of chronic recurrent spontaneous limbic seizures in rats. A single 90-minute period of repetitive electrical stimulation (inducing stimulus) of the hippocampus in rats elicited a single episode of status epilepticus, followed by a 2- to 4-week seizure-free period. Spontaneous recurrent seizures developed subsequently and persisted for the duration of monitoring (2-10 months). Simultaneous computerized electroencephalography and video recording were used to monitor the animals. After the establishment of spontaneous recurrent seizures, bilateral radiation centered in the ventral hippocampal formation was administered with the Leksell gamma knife, aided by a stereotactic device custom made for small animals. A center dose of 10, 20, or 40 Gy was administered using a 4-mm collimator. Control animals were subjected to the same seizure-inducing stimulus but underwent a sham treatment instead of gamma irradiation. In a second experiment, the authors examined the effects of gamma irradiation on the proclivity of hippocampal neurons to display epileptiform discharges. Naive animals were irradiated with a single 40-Gy dose, as already described. Slices of the hippocampus were prepared from animals killed between 1 and 178 days postirradiation. Sensitivity to penicillin-induced epileptiform spiking was examined in vitro in slices prepared from control and irradiated rat brains. In the first experiment, single doses of 20 or 40 Gy (but not 10 Gy) reduced substantially, and in some cases eliminated, behaviorally and

  11. Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1/TLR4/NF-κB pathway following experimental traumatic brain injury.

    Science.gov (United States)

    Chen, Xiangrong; Wu, Shukai; Chen, Chunnuan; Xie, Baoyuan; Fang, Zhongning; Hu, Weipeng; Chen, Junyan; Fu, Huangde; He, Hefan

    2017-07-24

    Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) to activate downstream signaling pathways, such as the nuclear factor (NF)-κB signaling pathway, leading to a cascade amplification of inflammatory responses, which are related to neuronal damage after TBI. Omega-3 polyunsaturated fatty acid (ω-3 PUFA) is a commonly used clinical immunonutrient, which has antioxidative and anti-inflammatory effects. However, the effects of ω-3 PUFA on HMGB1 expression and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway are not clear. The Feeney DM TBI model was adopted to induce brain injury in rats. Modified neurological severity scores, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Assessment of microglial activation in lesioned sites and protein markers for proinflammatory, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ, and HMGB1 were used to evaluate neuroinflammatory responses and anti-inflammation effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation, secretion, and HMGB1-mediated activation of the TLR4/NF-κB signaling pathway to evaluate the effects of ω-3 PUFA supplementation and gain further insight into the mechanisms underlying the development of the neuroinflammatory response after TBI. It was found that ω-3 PUFA supplementation inhibited TBI-induced microglial activation and expression of inflammatory factors (TNF-α, IL-1β, IL-6, and IFN-γ), reduced brain edema, decreased neuronal apoptosis, and improved neurological

  12. Capgras syndrome associated with limbic encephalitis in a patient with diffuse large B-cell lymphoma

    OpenAIRE

    Soares Neto, Herval Ribeiro; Cavalcante, Wagner Cid Palmeira; Martins Filho, Sebastião Nunes; Smid, Jerusa; Nitrini, Ricardo

    2016-01-01

    We report the case of a patient with insidious onset and slowly progressive cognitive impairment, behavioral symptoms, temporal lobe seizures and delusional thoughts typical of delusional misidentification syndromes. Clinical presentation along with extensive diagnostic work-up revealed limbic encephalitis secondary to diffuse large B-cell lymphoma. The patient underwent immunotherapy with high-dose corticosteroid but no significant improvement was observed. No specific treatment for lymphoma...

  13. Limbic encephalitis with antibodies to glutamic acid decarboxylase presenting with brainstem symptoms

    Directory of Open Access Journals (Sweden)

    Faruk Incecik

    2015-01-01

    Full Text Available Limbic encephalitis (LE is a neurological syndrome that may present in association with cancer, infection, or as an isolate clinical condition often accompanying autoimmune disorders. LE associated with glutamic acid decarboxylase antibodies (anti-GAD is rare in children. Here, we characterized the clinical and laboratory features of a patient presenting with brainstem involvement with non-paraneoplastic LE associated with anti-GAD antibodies. In our patient, after plasma exchange, we determined a dramatic improvement of the neurological deficits.

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

    Science.gov (United States)

    Misawa, Tamako; Mizusawa, Hidehiro

    2010-04-01

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

  15. Fish oil feeding attenuates neuroinflammatory gene expression without concomitant changes in brain eicosanoids and docosanoids in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Hopperton, Kathryn E; Trépanier, Marc-Olivier; James, Nicholas C E; Chouinard-Watkins, Raphaël; Bazinet, Richard P

    2018-03-01

    Neuroinflammation is a recognized hallmark of Alzheimer's disease, along with accumulation of amyloid-β plaques, neurofibrillary tangles and synaptic loss. n-3 polyunsaturated fatty acids (PUFA) and molecules derived from them, including eicosapentaenoic acid-derived eicosanoids and docosahexaenoic acid-derived docosanoids, are known to have both anti-inflammatory and pro-resolving properties, while human observational data links consumption of these fatty acids to a decreased risk of Alzheimer's disease. Few studies have examined the neuroinflammation-modulating effects of n-3 PUFA feeding in an Alzheimer's disease-related model, and none have investigated whether these effects are mediated by changes in brain eicosanoids and docosanoids. Here, we use both a fat-1 transgenic mouse and a fish oil feeding model to study the impact of increasing tissue n-3 PUFA on neuroinflammation and the production of pro-inflammatory and pro-resolving lipid mediators. Fat-1 mice, transgenic animals that can convert n-6 to n-3 PUFA, and their wildtype littermates were fed diets containing either fish oil (high n-3 PUFA) or safflower oil (negligible n-3 PUFA) from weaning to 12 weeks. Animals then underwent intracerebroventricular infusion of either amyloid-β 1-40 or a control peptide. Hippocampi were collected from non-surgery and surgery animals 10 days after infusion. Microarray was used to measure enrichment of inflammation-associated gene categories and expression of genes involved in the synthesis of lipid mediators. Results were validated by real-time PCR in a separate cohort of animals. Lipid mediators were measured via liquid chromatography tandem mass spectrometry. Fat-1 and wildtype mice fed fish oil had higher total hippocampal DHA than wildtype mice fed the safflower oil diet. The safflower-fed mice, but not the fat-1 or fish oil-fed mice, had significantly increased expression in gene ontology categories associated with inflammation in response to amyloid

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

    Science.gov (United States)

    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

  17. Limbic system, the main focus of dementia syndrome; A study with MRI and PET

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzawa, Taiju [Morinosato Hospital, Atsugi, Kanagawa (Japan)

    1990-12-01

    Alzheimer disease and multi-infarct dementia are two entirely different diseases producing almost the same abnormalities as dementia syndrome. The statistical studies with MRI to locate the focus of dementia syndrome in the neocortex was an absolute failure. With MRI there is drastic atrophy and destruction of the amygdala and hippocampus suggesting the limbic system as the focus of dementia syndrome. Destruction of the limbic system in particular amygdala and hippocampus produced the functional obstruction brought about by the marked reduction in the glucose utilization with PET in the bilateral temporal, parietal and occipital association cortices. Although this type constitutes only about 1/5 of all dementia patients. It is considered the fundamental type of dementia syndrome. Aside from this, there is a type wherein simultaneous and symmetrical reductions in glucose utilization of the frontal association cortex and the motor association cortex in the anterior part of the neocortex. This is referred to as type II. It constitutes about 4/5 of all dementia patients which is far more than type I. Based on these results, it is thought that limbic system is the main focus of dementia syndrome. (author).

  18. Betacyanins from Portulaca oleracea L. ameliorate cognition deficits and attenuate oxidative damage induced by D-galactose in the brains of senescent mice.

    Science.gov (United States)

    Wang, Chang-Quan; Yang, Gui-Qin

    2010-06-01

    This experiment was designed to assess the protective effect of betacyanins from Portulaca oleracea L. against the D-galactose (D-gal)-induced neurotoxicity in mice. Betacyanins from Portulaca oleracea markedly reversed the D-gal-induced learning and memory impairments, as measured by behavioral tests. The activities of superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in D-gal-treated mice were enhanced, while the content of the lipid peroxidation product malondialdehyde (MDA) was decreased by betacyanin administration. Furthermore, significant negative correlations were found between mouse latency in finding the platform and the activities of SOD, CAT GR and GPx in the mouse brain, but the level of MDA correlated positively with the latency. These results suggest that the neuroprotective effect of betacyanins against D-gal-induced neurotoxicity might be caused, at least in part, by an increase in the activities of antioxidant enzymes with a reduction in lipid peroxidation. In comparison with vitamin C (VC), the betacyanins had a more pronounced effect on ameliorating cognition deficits in mice.

  19. The association atorvastatin-meloxicam reduces brain damage, attenuating reactive gliosis subsequent to arterial embolism = La asociación atorvastatina-meloxicam reduce el daño cerebral, atenuando la gliosis reactiva consecuente a embolismo arterial

    Directory of Open Access Journals (Sweden)

    Marcela Hernández Torres

    2013-10-01

    Full Text Available The association atorvastatin-meloxicam reduces brain damage, attenuating reactive gliosis subsequent to arterial embolism Introduction: Stroke is the leading cause of disability and the third of death in Colombia and in the world and it is associated with neurodegenerative and mental diseases. Objective: To determine the effects of the atorvastatin- meloxicam association on reactive gliosis in a model of cerebral ischemia produced by arterial embolization. Materials and methods: 56 adult male Wistar rats were used, divided into four ischemic and four control groups, plus 10 additional animals to determine the distribution and extent of infarction by injury in six of them and simulation (sham in the remaining four. The treatments were: placebo, atorvastatin (ATV, meloxicam (MELOX and ATV + MELOX in ischemic and simulated animals. 24 hours post-ischemia mitochondrial enzymatic activity was evaluated with triphenyl- tetrazolium (TTC, and at 120 hours astrocytic reactivity (anti-GFAP was analyzed by conventional immunohistochemistry. Results: The association ATV + MELOX favored the modulation of the response of protoplasmatic and fibrous astrocytes in both the hippocampus and the paraventricular zone by reducing their hypereactivity. Conclusion: Atorvastatin and meloxicam, either individually or associated, reduce cerebral damage by lessening the reactive gliosis produced by arterial embolization; this suggests new mechanisms of neuroprotection against thromboembolic cerebral ischemia, and opens new perspectives in its early treatment.

  20. Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex.

    Science.gov (United States)

    Chiba, Shuichi; Numakawa, Tadahiro; Ninomiya, Midori; Richards, Misty C; Wakabayashi, Chisato; Kunugi, Hiroshi

    2012-10-01

    Stress and the resulting increase in glucocorticoid levels have been implicated in the pathophysiology of depressive disorders. We investigated the effects of chronic restraint stress (CRS: 6 hours × 28 days) on anxiety- and depression-like behaviors in rats and on the possible changes in glucocorticoid receptor (GR) expression as well as brain-derived neurotrophic factor (BDNF)-dependent neural function in the prefrontal cortex (PFC). We observed significant reductions in body weight gain, food intake and sucrose preference from 1 week after the onset of CRS. In the 5th week of CRS, we conducted open-field (OFT), elevated plus-maze (EPM) and forced swim tests (FST). We observed a decrease in the number of entries into open arms during the EPM (anxiety-like behavior) and increased immobility during the FST (depression-like behavior). When the PFC was removed after CRS and subject to western blot analysis, the GR expression reduced compared with control, while the levels of BDNF and its receptors remained unchanged. Basal glutamate concentrations in PFC acute slice which were measured by high performance liquid chromatography were not influenced by CRS. However, BDNF-induced glutamate release was attenuated after CRS. These results suggest that reduced GR expression and altered BDNF function may be involved in chronic stress-induced anxiety--and depression-like behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Positive parenting predicts the development of adolescent brain structure: A longitudinal study

    Directory of Open Access Journals (Sweden)

    Sarah Whittle

    2014-04-01

    Full Text Available Little work has been conducted that examines the effects of positive environmental experiences on brain development to date. The aim of this study was to prospectively investigate the effects of positive (warm and supportive maternal behavior on structural brain development during adolescence, using longitudinal structural MRI. Participants were 188 (92 female adolescents, who were part of a longitudinal adolescent development study that involved mother–adolescent interactions and MRI scans at approximately 12 years old, and follow-up MRI scans approximately 4 years later. FreeSurfer software was used to estimate the volume of limbic-striatal regions (amygdala, hippocampus, caudate, putamen, pallidum, and nucleus accumbens and the thickness of prefrontal regions (anterior cingulate and orbitofrontal cortices across both time points. Higher frequency of positive maternal behavior during the interactions predicted attenuated volumetric growth in the right amygdala, and accelerated cortical thinning in the right anterior cingulate (males only and left and right orbitofrontal cortices, between baseline and follow up. These results have implications for understanding the biological mediators of risk and protective factors for mental disorders that have onset during adolescence.

  2. Positive parenting predicts the development of adolescent brain structure: a longitudinal study.

    Science.gov (United States)

    Whittle, Sarah; Simmons, Julian G; Dennison, Meg; Vijayakumar, Nandita; Schwartz, Orli; Yap, Marie B H; Sheeber, Lisa; Allen, Nicholas B

    2014-04-01

    Little work has been conducted that examines the effects of positive environmental experiences on brain development to date. The aim of this study was to prospectively investigate the effects of positive (warm and supportive) maternal behavior on structural brain development during adolescence, using longitudinal structural MRI. Participants were 188 (92 female) adolescents, who were part of a longitudinal adolescent development study that involved mother-adolescent interactions and MRI scans at approximately 12 years old, and follow-up MRI scans approximately 4 years later. FreeSurfer software was used to estimate the volume of limbic-striatal regions (amygdala, hippocampus, caudate, putamen, pallidum, and nucleus accumbens) and the thickness of prefrontal regions (anterior cingulate and orbitofrontal cortices) across both time points. Higher frequency of positive maternal behavior during the interactions predicted attenuated volumetric growth in the right amygdala, and accelerated cortical thinning in the right anterior cingulate (males only) and left and right orbitofrontal cortices, between baseline and follow up. These results have implications for understanding the biological mediators of risk and protective factors for mental disorders that have onset during adolescence. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Distorted images of one's own body activates the prefrontal cortex and limbic/paralimbic system in young women: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Kurosaki, Mitsuhaya; Shirao, Naoko; Yamashita, Hidehisa; Okamoto, Yasumasa; Yamawaki, Shigeto

    2006-02-15

    Our aim was to study the gender differences in brain activation upon viewing visual stimuli of distorted images of one's own body. We performed functional magnetic resonance imaging on 11 healthy young men and 11 healthy young women using the "body image tasks" which consisted of fat, real, and thin shapes of the subject's own body. Comparison of the brain activation upon performing the fat-image task versus real-image task showed significant activation of the bilateral prefrontal cortex and left parahippocampal area including the amygdala in the women, and significant activation of the right occipital lobe including the primary and secondary visual cortices in the men. Comparison of brain activation upon performing the thin-image task versus real-image task showed significant activation of the left prefrontal cortex, left limbic area including the cingulate gyrus and paralimbic area including the insula in women, and significant activation of the occipital lobe including the left primary and secondary visual cortices in men. These results suggest that women tend to perceive distorted images of their own bodies by complex cognitive processing of emotion, whereas men tend to perceive distorted images of their own bodies by object visual processing and spatial visual processing.

  4. Tinnitus distress is linked to enhanced resting-state functional connectivity from the limbic system to the auditory cortex.

    Science.gov (United States)

    Chen, Yu-Chen; Xia, Wenqing; Chen, Huiyou; Feng, Yuan; Xu, Jin-Jing; Gu, Jian-Ping; Salvi, Richard; Yin, Xindao

    2017-05-01

    The phantom sound of tinnitus is believed to be triggered by aberrant neural activity in the central auditory pathway, but since this debilitating condition is often associated with emotional distress and anxiety, these comorbidities likely arise from maladaptive functional connections to limbic structures such as the amygdala and hippocampus. To test this hypothesis, resting-state functional magnetic resonance imaging (fMRI) was used to identify aberrant effective connectivity of the amygdala and hippocampus in tinnitus patients and to determine the relationship with tinnitus characteristics. Chronic tinnitus patients (n = 26) and age-, sex-, and education-matched healthy controls (n = 23) were included. Both groups were comparable for hearing level. Granger causality analysis utilizing the amygdala and hippocampus as seed regions were used to investigate the directional connectivity and the relationship with tinnitus duration or distress. Relative to healthy controls, tinnitus patients demonstrated abnormal directional connectivity of the amygdala and hippocampus, including primary and association auditory cortex, and other non-auditory areas. Importantly, scores on the Tinnitus Handicap Questionnaires were positively correlated with increased connectivity from the left amygdala to left superior temporal gyrus (r = 0.570, P = 0.005), and from the right amygdala to right superior temporal gyrus (r = 0.487, P = 0.018). Moreover, enhanced effective connectivity from the right hippocampus to left transverse temporal gyrus was correlated with tinnitus duration (r = 0.452, P = 0.030). The results showed that tinnitus distress strongly correlates with enhanced effective connectivity that is directed from the amygdala to the auditory cortex. The longer the phantom sensation, the more likely acute tinnitus becomes permanently encoded by memory traces in the hippocampus. Hum Brain Mapp 38:2384-2397, 2017. © 2017 Wiley Periodicals, Inc.

  5. Impaired c-Fos and polo-like kinase 2 induction in the limbic system of fear-conditioned α-synuclein transgenic mice.

    Directory of Open Access Journals (Sweden)

    Heinrich Schell

    Full Text Available α-Synuclein (αSYN is genetically and neuropathologically linked to a spectrum of neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies, and related disorders. Cognitive impairment is recapitulated in several αSYN transgenic mouse lines. However, the mechanisms of dysfunction in affected neurons are largely unknown. Here we measured neuronal activity induced gene products in the limbic system of αSYN transgenic mice upon fear conditioning (FC. Induction of the synaptic plasticity marker c-Fos was significantly reduced in the amygdala and hippocampus of (Thy1-h[A30P]αSYN transgenic mice in an age-dependent manner. Similarly, the neuronal activity inducible polo-like kinase 2 (Plk2 that can phosphorylate αSYN at the pathological site serine-129 was up-regulated in both brain regions upon FC. Plk2 inductions were also significantly impaired in aged (Thy1-h[A30P]αSYN transgenic mice, both in the amygdala and hippocampus. Plk2 inductions in the amygdala after FC were paralleled by a small but significant increase in the number of neuronal cell bodies immunopositive for serine-129 phosphorylated αSYN in young but not aged (Thy1-h[A30P]αSYN transgenic mice. In addition, we observed in the aged hippocampus a distinct type of apparently unmodified transgenic αSYN profiles resembling synaptic accumulations of αSYN. Thus, the cognitive decline observed in aged αSYN transgenic mice might be due to impairment of neurotransmission and synaptic plasticity in the limbic system by distinct αSYN species.

  6. Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: an event-related fMRI study.

    Science.gov (United States)

    Minzenberg, Michael J; Fan, Jin; New, Antonia S; Tang, Cheuk Y; Siever, Larry J

    2007-08-15

    Clinical hallmarks of borderline personality disorder (BPD) include social and emotional dysregulation. We tested a model of fronto-limbic dysfunction in facial emotion processing in BPD. Groups of 12 unmedicated adults with BPD by DSM-IV and 12 demographically-matched healthy controls (HC) viewed facial expressions (Conditions) of neutral emotion, fear and anger, and made gender discriminations during rapid event-related functional magnetic resonance imaging (fMRI). Analysis of variance of Region of Interest signal change revealed a statistically significant effect of the Group-by-Region-by-Condition interaction. This was due to the BPD group exhibiting a significantly larger magnitude of deactivation (relative to HC) in the bilateral rostral/subgenual anterior cingulate cortex (ACC) to fear and in the left ACC to fear minus neutral; and significantly greater activation in the right amygdala to fear minus neutral. There were no significant between-group differences in ROI signal change in response to anger. In voxel-wise analyses constrained within these ROIs, the BPD group exhibited significant changes in the fear minus neutral contrast, with relatively less activation in the bilateral rostral/subgenual ACC, and greater activation in the right amygdala. In the anger minus neutral contrast this pattern was reversed, with the BPD group showing greater activation in the bilateral rostral/subgenual ACC and less activation in the bilateral amygdala. We conclude that adults with BPD exhibit changes in fronto-limbic activity in the processing of fear stimuli, with exaggerated amygdala response and impaired emotion-modulation of ACC activity. The neural substrates underlying processing of anger may also be altered. These changes may represent an expression of the volumetric and serotonergic deficits observed in these brain areas in BPD.

  7. Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

    Science.gov (United States)

    Ciumas, Carolina; Lindström, Per; Aoun, Bernard; Savic, Ivanka

    2008-01-15

    Metabolic and neuro-receptor abnormalities within the extrafocal limbic circuits are established in mesial temporal lobe epilepsy (MTLE). However, very little is known about how these circuits process external stimuli. We tested whether odor activation can help delineate limbic functional disintegration in MTLE, and measured cerebral blood flow with PET during birhinal smelling of familiar and unfamiliar odors, using smelling of odorless air as the baseline condition. Patients with MTLE (13 left-sided, 10 right-sided) and 21 controls were investigated. In addition to odor activation, the analysis included functional connectivity, using right and left piriform cortex as seed regions. Healthy controls activated the amygdala, piriform, anterior insular, and cingulate cortices on both sides. Smelling of familiar odors engaged, in addition, the right parahippocampus, and the left Brodmann Area (BA) 44, 45, 47. Patients failed to activate the amygdala, piriform and the anterior insular cortex in the epileptogenic hemisphere. Furthermore, those with left MTLE did not activate the left BA 44, 45 and 47 with familiar odors, which they perceived as less familiar than controls. Congruent with the activation data each seed region was in patients functionally disconnected with the contralateral amygdala+piriform+insular cortex. The functional disintegration in patients exceeded the reduced activation, and included the contralateral temporal neocortex, and in subjects with right MTLE also the right orbitofrontal cortex. Imaging of odor perception may be used to delineate functional disintegration of the limbic networks in MTLE. It shows an altered response in several regions, which may underlie some interictal behavioral problems associated with this condition.

  8. Cortisol awakening response and negative emotionality linked to asymmetry in major limbic fibre bundle architecture

    DEFF Research Database (Denmark)

    Madsen, Kathrine Skak; Jernigan, Terry L; Iversen, Pernille

    2012-01-01

    associated with higher CAR, were also correlated with higher right relative to left cingulum FA. Elevated CAR was associated with the degree of FA asymmetry within both the cingulum and the uncinate fasciculus, but in opposing directions. These results suggest that the balance between left- and right......The limbic system plays an important role in regulating the hypothalamic-pituitary-adrenal (HPA) axis as well as aspects of emotion, and both neuroendocrine disturbance and increased negative emotionality are associated with risk for developing affective disorders. However, the extent to which...

  9. Omega-3 polyunsaturated fatty acid attenuates the inflammatory response by modulating microglia polarization through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway following experimental traumatic brain injury.

    Science.gov (United States)

    Chen, Xiangrong; Chen, Chunnuan; Fan, Sining; Wu, Shukai; Yang, Fuxing; Fang, Zhongning; Fu, Huangde; Li, Yasong

    2018-04-20

    development of the neuroinflammatory response after TBI. The results of our study showed that ω-3 PUFA supplementation promoted a shift from the M1 microglial phenotype to the M2 microglial phenotype and inhibited microglial activation, thus reducing TBI-induced inflammatory factors. In addition, ω-3 PUFA-mediated downregulation of HMGB1 acetylation and its extracellular secretion was found to be likely due to increased SIRT1 activity. We also found that treatment with ω-3 PUFA inhibited HMGB1 acetylation and induced direct interactions between SIRT1 and HMGB1 by elevating SIRT1 activity following TBI. These events lead to inhibition of HMGB1 nucleocytoplasmic translocation/extracellular secretion and alleviated HMGB1-mediated activation of the NF-κB pathway following TBI-induced microglial activation, thus inhibiting the subsequent inflammatory response. The results of this study suggest that ω-3 PUFA supplementation attenuates the inflammatory response by modulating microglial polarization through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway, leading to neuroprotective effects following experimental traumatic brain injury.

  10. Dissipation and spontaneous symmetry breaking in brain dynamics

    International Nuclear Information System (INIS)

    Freeman, Walter J; Vitiello, Giuseppe

    2008-01-01

    We compare the predictions of the dissipative quantum model of the brain with neurophysiological data collected from electroencephalograms resulting from high-density arrays fixed on the surfaces of primary sensory and limbic areas of trained rabbits and cats. Functional brain imaging in relation to behavior reveals the formation of coherent domains of synchronized neuronal oscillatory activity and phase transitions predicted by the dissipative model

  11. The usefulness of the ivy sign on fluid-attenuated intensity recovery images in improved brain hemodynamic changes after superficial temporal artery-middle cerebral artery anastomosis in adult patients with moyamoya disease.

    Science.gov (United States)

    Lee, Jung Keun; Yoon, Byul Hee; Chung, Seung Young; Park, Moon Sun; Kim, Seong Min; Lee, Do Sung

    2013-10-01

    MR perfusion and single photon emission computerized tomography (SPECT) are well known imaging studies to evaluate hemodynamic change between prior to and following superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis in moyamoya disease. But their side effects and invasiveness make discomfort to patients. We evaluated the ivy sign on MR fluid attenuated inversion recovery (FLAIR) images in adult patients with moyamoya disease and compared it with result of SPECT and MR perfusion images. We enrolled twelve patients (thirteen cases) who were diagnosed with moyamoya disease and underwent STA-MCA anastomosis at our medical institution during a period ranging from September of 2010 to December of 2012. The presence of the ivy sign on MR FLAIR images was classified as Negative (0), Minimal (1), and Positive (2). Regions were classified into four territories: the anterior cerebral artery (ACA), the anterior MCA, the posterior MCA and the posterior cerebral artery. Ivy signs on preoperative and postoperative MR FLAIR were improved (8 and 4 in the ACA regions, 13 and 4 in the anterior MCA regions and 19 and 9 in the posterior MCA regions). Like this result, the cerebrovascular reserve (CVR) on SPECT was significantly increased in the sum of CVR in same regions after STA-MCA anastomosis. After STA-MCA anastomosis, ivy signs were decreased in the cerebral hemisphere. As compared with conventional diagnostic modalities such as SPECT and MR perfusion images, the ivy sign on MR FLAIR is considered as a useful indicator in detecting brain hemodynamic changes between preoperatively and postoperatively in adult moyamoya patients.

  12. Tracer attenuation in groundwater

    Science.gov (United States)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  13. Determination of the attenuation map in emission tomography

    CERN Document Server

    Zaidi, H

    2002-01-01

    Reliable attenuation correction methods for quantitative emission computed tomography (ECT) require accurate delineation of the body contour and often necessitate knowledge of internal anatomical structure. Two broad classes of methods have been used to calculate the attenuation map referred to as "transmissionless" and transmission-based attenuation correction techniques. While calculated attenuation correction belonging to the first class of methods is appropriate for brain studies, more adequate methods must be performed in clinical applications where the attenuation coefficient distribution is not known a priori, and for areas of inhomogeneous attenuation such as the chest. Measured attenuation correction overcomes this problem and utilizes different approaches to determine this map including transmission scanning, segmented magnetic resonance images or appropriately scaled X-ray CT scans acquired either independently on separate or simultaneously on multimodality imaging systems. Combination of data acqu...

  14. Metabolic mapping of the effects of the antidepressant fluoxetine on the brains of congenitally helpless rats

    OpenAIRE

    Shumake, Jason; Colorado, Rene A.; Barrett, Douglas W.; Gonzalez-Lima, F.

    2010-01-01

    Antidepressants require adaptive brain changes before efficacy is achieved, and they may impact the affectively disordered brain differently than the normal brain. We previously demonstrated metabolic disturbances in limbic and cortical regions of the congenitally helpless rat, a model of susceptibility to affective disorder, and we wished to test whether administration of fluoxetine would normalize these metabolic differences. Fluoxetine was chosen because it has become a first-line drug for...

  15. Limbic encephalitis associated with anti-NH2-terminal of α-enolase antibodies

    Science.gov (United States)

    Kishitani, Toru; Matsunaga, Akiko; Ikawa, Masamichi; Hayashi, Kouji; Yamamura, Osamu; Hamano, Tadanori; Watanabe, Osamu; Tanaka, Keiko; Nakamoto, Yasunari; Yoneda, Makoto

    2017-01-01

    Abstract Several types of autoantibodies have been reported in autoimmune limbic encephalitis (LE), such as antibodies against the voltage-gated potassium channel (VGKC) complex including leucine-rich glioma inactivated 1 (LGI1). We recently reported a patient with autoimmune LE and serum anti-NH2-terminal of α-enolase (NAE) antibodies, a specific diagnostic marker for Hashimoto encephalopathy (HE), who was diagnosed with HE based on the presence of antithyroid antibodies and responsiveness to immunotherapy. This case suggests that LE patients with antibodies to both the thyroid and NAE could be diagnosed with HE and respond to immunotherapy. The aim of this study was to clarify the clinicoimmunological features and efficacy of immunotherapy in LE associated with anti-NAE antibodies to determine whether the LE is a clinical subtype of HE. We examined serum anti-NAE antibodies in 78 LE patients with limbic abnormality on magnetic resonance imaging and suspected HE based on positivity for antithyroid antibodies. Nineteen of the 78 patients had anti-NAE antibodies; however, 5 were excluded because they were double positive for antibodies to the VGKC complex including LGI1. No antibodies against the N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (Caspr2), γ-aminobutyric acid-B receptor (GABABR), or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) were detected in the 19 patients. Among the remaining 14 who were positive only for anti-NAE antibodies, the median age was 62.5 (20–83) years, 9 (64%) were women, and 8 (57%) showed acute onset, with less than 2 weeks between onset and admission. Consciousness disturbance (71%) and memory disturbance (64%) were frequently observed, followed by psychiatric symptoms (50%) and seizures (43%). The frequency of these symptoms significantly differed between the acute- and subacute-onset groups. Abnormalities in cerebrospinal fluid and electroencephalogram were commonly observed (92

  16. Reversible Dementia: Two Nursing Home Patients With Voltage-Gated Potassium Channel Antibody-Associated Limbic Encephalitis

    NARCIS (Netherlands)

    Reintjes, W.; Romijn, M.D.M.; den Hollander, D.; ter Bruggen, J.P.; van Marum, R.J.

    2015-01-01

    Voltage-gated potassium channel antibody-associated limbic encephalitis (VGKC-LE) is a rare disease that is a diagnostic and therapeutic challenge for medical practitioners. Two patients with VGKC-LE, both developing dementia are presented. Following treatment, both patients showed remarkable

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

    Science.gov (United States)

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

    2018-06-01

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

  18. Limbic system associated membrane protein as a potential target for neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Eero eVasar

    2013-03-01

    Full Text Available The studies performed in laboratory animals and psychiatric patients suggest a possible role of limbic system associated membrane protein (LAMP in the mechanisms of psychiatric disorders. Stressful manipulations and genetic invalidation have revealed a role of the Lsamp gene in the regulation of anxiety in rodents. Besides that, Lsamp deficient mice display reduced aggressiveness and impaired adaptation in novel and stressful environments. The behavioural effects of amphetamine were blunted in genetically modified mice. Recent pharmacological and biochemical studies point towards altered function of GABA-, 5-hydroxytryptamine- and dopaminergic systems in Lsamp deficient mice. Moreover, we found an association between the gene polymorphisms of LSAMP and major depressive disorder. Patients suffering from major depressive disorder had significantly increased ratio between risk and protective haplotypes of the LSAMP gene compared to healthy volunteers. However, the impact of these haplotypes for the function of LAMP is not clear and remains to be elucidated in future studies.

  19. Unusual amnesia in a patient with VGKC-Ab limbic encephalitis: a case study.

    Science.gov (United States)

    Kartsounis, Luke D; de Silva, Rajith

    2011-04-01

    We describe the case of a patient with confirmed voltage-gated potassium channel antibody-associated encephalitis (VGKC-Ab). MRI studies revealed bilateral hyper-intensity in the hippocampi, with their volumes preserved. At presentation, the patient's anterograde and retrograde memory skills were found to be impaired and he showed fluctuation in his ability to recall familiar information. Following treatment with immunotherapy, his condition improved considerably and, in a series of follow up assessments, he performed satisfactorily (i.e., within the average range or above) on formal tests of memory, as well as on a range of other cognitive tests, including tests of executive function. By contrast, in the context of contemporaneous unstructured interviews, he showed a strong tendency to confabulate. We argue that the reported case broadens the phenomenology of VGKC-Ab limbic encephalitis and raises important theoretical questions about the aetiology of this patient's most unusual memory disorder. Copyright © 2010 Elsevier Srl. All rights reserved.

  20. Neonatal ventral hippocampus lesion alters the dopamine content in the limbic regions in postpubertal rats.

    Science.gov (United States)

    Alquicer, Glenda; Silva-Gómez, Adriana B; Peralta, Fernando; Flores, Gonzalo

    2004-04-01

    The neonatal ventral Hippocampus (nVH) lesion in rats has been used as a model to test the hypothesis that early neurodevelopmental abnormalities lead to behavioral changes putatively linked to schizophrenia. The schizophrenic patients tend to social isolation. In addition, considerable evidence from behavioral and neurochemistry studies strongly implicate the dopamine (DA) system and the medial part of the prefrontal cortex (mPFC) in the pathophysiology of the social isolation syndrome. In order to assess effects of the postweaning social isolation (pwSI) on the DA system of the nVH lesions, we investigated the DA content and its metabolite, DOPAC in different limbic subregions in rats postpubertally at postnatal day (P) 78 following nVH lesions at P7 with and without pwSI for 8 weeks. The DA and DOPAC were measured by HPLC with electrochemical detection. The nVH lesion induces increase in the DA content in the hippocampus with no effect in the mPFC, nucleus accumbens and caudate-putamen, while the pwSI induces major increase in the DA content in limbic subregions such as the mPFC, nucleus accumbens and hipocampus with opposite effect in the caudate-putamen. These results suggest that while pwSI has an effect in the postpubertal content of DA in both sham and nVH lesions in rats, the nVH-lesioned rats appear to be affected to a greater extent than the sham animals underscoring the influence of pwSI differences in the development of behaviors in the nVH-lesioned animals.

  1. Traumatic Brain Injury: A Guide for Caregivers of Service Members and Veterans

    Science.gov (United States)

    2010-01-01

    Neuropsychological Evaluation...Module 2, page 35 Neuropsychologist - Module 2, pages 9, 35 Neuropsychology - Companion, page 7 Neuroradiological Tests - Companion, page 7 Neurosurgeon...temperature • hunger • thirst • emotional and behavior responses. Directly beneath the cerebrum is the limbic system. This part of the brain

  2. GABAergic Signaling within a Limbic-Hypothalamic Circuit Integrates Social and Anxiety-Like Behavior with Stress Reactivity.

    Science.gov (United States)

    Myers, Brent; Carvalho-Netto, Eduardo; Wick-Carlson, Dayna; Wu, Christine; Naser, Sam; Solomon, Matia B; Ulrich-Lai, Yvonne M; Herman, James P

    2016-05-01

    The posterior hypothalamic nucleus (PH) stimulates autonomic stress responses. However, the role of the PH in behavioral correlates of psychiatric illness, such as social and anxiety-like behavior, is largely unexplored, as is the neurochemistry of PH connectivity with limbic and neuroendocrine systems. Thus, the current study tested the hypothesis that GABAergic signaling within the PH is a critical link between forebrain behavior-regulatory nuclei and the neuroendocrine hypothalamus, integrating social and anxiety-related behaviors with physiological stress reactivity. To address this hypothesis, GABAA receptor pharmacology was used to locally inhibit or disinhibit the PH immediately before behavioral measures of social and anxiety-like behavior in rats. Limbic connectivity of the PH was then established by simultaneous co-injection of anterograde and retrograde tracers. Further, the role of PH GABAergic signaling in neuroendocrine stress responses was tested via inhibition/disinhibition of the PH. These studies determined a prominent role for the PH in the expression of anxiety-related behaviors and social withdrawal. Histological analyses revealed divergent stress-activated limbic input to the PH, emanating predominantly from the prefrontal cortex, lateral septum, and amygdala. PH projections also targeted both parvicellular and magnocellular peptidergic neurons in the paraventricular and supraoptic hypothalamus. Further, GABAA receptor pharmacology determined an excitatory effect of the PH on neuroendocrine responses to stress. These data indicate that the PH represents an important stress-integrative center, regulating behavioral processes and connecting the limbic forebrain with neuroendocrine systems. Moreover, the PH appears to be uniquely situated to have a role in stress-related pathologies associated with limbic-hypothalamic dysfunction.

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

    Science.gov (United States)

    Zhong, Xue; Pu, Weidan; Yao, Shuqiao

    2016-12-01

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

  4. Attenuation of the gamma rays in tissues

    International Nuclear Information System (INIS)

    Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Amador V, P.; Chacon R, A.; Vega C, H.R.

    2005-01-01

    The mass and lineal attenuation coefficient and of hepatic tissue, muscular, osseous and of brain before gamma rays of 10 -3 to 10 5 MeV were calculated. For the case of the osseous tissue the calculation was made for the cartilage, the cortical tissue and the bone marrow. During the calculations the elementary composition of the tissues of human origin was used. The calculations include by separate the Photoelectric effect, the Compton scattering and the Pair production, as well as the total. For to establish a comparison with the attenuation capacities, the coefficients of the water, the aluminum and the lead also were calculated. The study was complemented measuring the attenuation coefficient of hepatic tissue of bovine before gamma rays of 0.662 MeV of a source of 137 Cs. The measurement was made through of an experiment of photons transmission through samples frozen of hepatic tissue and with a Geiger-Mueller detector. (Author)

  5. Attenuation correction for SPECT

    International Nuclear Information System (INIS)

    Hosoba, Minoru

    1986-01-01

    Attenuation correction is required for the reconstruction of a quantitative SPECT image. A new method for detecting body contours, which are important for the correction of tissue attenuation, is presented. The effect of body contours, detected by the newly developed method, on the reconstructed images was evaluated using various techniques for attenuation correction. The count rates in the specified region of interest in the phantom image by the Radial Post Correction (RPC) method, the Weighted Back Projection (WBP) method, Chang's method were strongly affected by the accuracy of the contours, as compared to those by Sorenson's method. To evaluate the effect of non-uniform attenuators on the cardiac SPECT, computer simulation experiments were performed using two types of models, the uniform attenuator model (UAM) and the non-uniform attenuator model (NUAM). The RPC method showed the lowest relative percent error (%ERROR) in UAM (11 %). However, 20 to 30 percent increase in %ERROR was observed for NUAM reconstructed with the RPC, WBP, and Chang's methods. Introducing an average attenuation coefficient (0.12/cm for Tc-99m and 0.14/cm for Tl-201) in the RPC method decreased %ERROR to the levels for UAM. Finally, a comparison between images, which were obtained by 180 deg and 360 deg scans and reconstructed from the RPC method, showed that the degree of the distortion of the contour of the simulated ventricles in the 180 deg scan was 15 % higher than that in the 360 deg scan. (Namekawa, K.)

  6. Landing gear noise attenuation

    Science.gov (United States)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

    2011-01-01

    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  7. Extensive superior limbic keratoconjunctivitis in Graves’ disease: case report and mini-review of the literature

    Directory of Open Access Journals (Sweden)

    Chelala E

    2015-03-01

    Full Text Available Elias Chelala, Hala El Rami, Ali Dirani, Henry Fakhoury, Ali Fadlallah Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon Background: Superior limbic keratoconjunctivitis (SLK is characterized as an inflammation of the superior bulbar conjunctiva with predominant involvement of the superior limbus and adjacent epithelial keratitis.Methods: A 51-year-old woman, with a history of medically controlled Graves’ disease was seen with an extensive SLK involving 5 mm of the superior cornea.Results: Total remission was observed with topical steroids (DXM. Recurrence was observed 1 week after steroid discontinuation, and steroidal treatment was reintroduced with tapering over 1 month. Total remission was then observed for 1 year. Conclusion: Extensive keratitis and vascular pannus in SLK is rarely reported. This form could be treated with topical steroids. Tapering treatment remains essential for long-term success. Keywords: superior limbic keratoconjunctivitis, anti-inflammatory drugs, dexamethasone, triamcinolone, Graves’ disease

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

    Science.gov (United States)

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

    2014-03-01

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

  9. Brain Oscillations, Hypnosis, and Hypnotizability.

    Science.gov (United States)

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

    2015-01-01

    This article summarizes the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, 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. The authors propose that this role may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis, specifically, that the increases in theta oscillations and 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.

  10. [Why do we call the brain 'brain'?

    Science.gov (United States)

    Garcia-Molina, A; Ensenat, A

    2017-01-16

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

  11. Supratentorial white matter blurring associated with voltage-gated potassium channel-complex limbic encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Urbach, H.; Mader, I. [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Rauer, S.; Baumgartner, A. [University Medical Center Freiburg, Department of Neurology, Freiburg (Germany); Paus, S. [University Medical Center, Department of Neurology, Bonn (Germany); Wagner, J. [University Medical Center, Department of Epileptology, Bonn (Germany); Malter, M.P. [University of Cologne, Department of Neurology, Cologne (Germany); Pruess, H. [Charite - Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Lewerenz, J.; Kassubek, J. [Ulm University, Department of Neurology, Ulm (Germany); Hegen, H.; Auer, M.; Deisenhammer, F. [University Innsbruck, Department of Neurology, Innsbruck (Austria); Ufer, F. [University Medical Center, Department of Neurology, Hamburg (Germany); Bien, C.G. [Epilepsy Centre Bethel, Bielefeld-Bethel (Germany)

    2015-12-15

    Limbic encephalitis (LE) associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) is frequently non-paraneoplastic and associated with marked improvement following corticosteroid therapy. Mesial temporal lobe abnormalities are present in around 80 % of patients. If associated or preceded by faciobrachial dystonic seizures, basal ganglia signal changes may occur. In some patients, blurring of the supratentorial white matter on T2-weighted images (SWMB) may be seen. The purpose of this study was to evaluate the incidence of SWMB and whether it is specific for VGKC-LE. Two experienced neuroradiologists independently evaluated signal abnormalities on FLAIR MRI in 79 patients with LE while unaware on the antibody type. SWMB was independently assessed as present in 10 of 36 (28 %) compared to 2 (5 %) of 43 non-VGKC patients (p = 0.009). It was not related to the presence of LGI1 or CASPR2 proteins of VGKC antibodies. MRI showed increased temporomesial FLAIR signal in 22 (61 %) VGKC compared to 14 (33 %) non-VGKC patients (p = 0.013), and extratemporomesial structures were affected in one VGKC (3 %) compared to 11 (26 %) non-VGKC patients (p = 0.005). SWMB is a newly described MRI sign rather specific for VGKC-LE. (orig.)

  12. Supratentorial white matter blurring associated with voltage-gated potassium channel-complex limbic encephalitis

    International Nuclear Information System (INIS)

    Urbach, H.; Mader, I.; Rauer, S.; Baumgartner, A.; Paus, S.; Wagner, J.; Malter, M.P.; Pruess, H.; Lewerenz, J.; Kassubek, J.; Hegen, H.; Auer, M.; Deisenhammer, F.; Ufer, F.; Bien, C.G.

    2015-01-01

    Limbic encephalitis (LE) associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) is frequently non-paraneoplastic and associated with marked improvement following corticosteroid therapy. Mesial temporal lobe abnormalities are present in around 80 % of patients. If associated or preceded by faciobrachial dystonic seizures, basal ganglia signal changes may occur. In some patients, blurring of the supratentorial white matter on T2-weighted images (SWMB) may be seen. The purpose of this study was to evaluate the incidence of SWMB and whether it is specific for VGKC-LE. Two experienced neuroradiologists independently evaluated signal abnormalities on FLAIR MRI in 79 patients with LE while unaware on the antibody type. SWMB was independently assessed as present in 10 of 36 (28 %) compared to 2 (5 %) of 43 non-VGKC patients (p = 0.009). It was not related to the presence of LGI1 or CASPR2 proteins of VGKC antibodies. MRI showed increased temporomesial FLAIR signal in 22 (61 %) VGKC compared to 14 (33 %) non-VGKC patients (p = 0.013), and extratemporomesial structures were affected in one VGKC (3 %) compared to 11 (26 %) non-VGKC patients (p = 0.005). SWMB is a newly described MRI sign rather specific for VGKC-LE. (orig.)

  13. Second primary tumor in anti-Ma1/2-positive paraneoplastic limbic encephalitis.

    Science.gov (United States)

    Leyhe, T; Schüle, R; Schwärzler, F; Gasser, T; Haarmeier, T

    2006-05-01

    Memory loss can be a symptom of paraneoplastic limbic encephalitis (PLE) a neuropsychiatric disorder associated mostly with small-cell lung cancer and anti-Hu antibodies or with testicular tumors and anti-Ma2 antibodies. We present the case of a patient with temporal coincidence of beginning cognitive decline and diagnosis of a carcinoma of the prostate in whom we diagnosed anti-Ma1/Ma2-positive PLE. The tumor had been completely resected but memory impairment further deteriorated. As the effective treatment of the cancer is considered as the most efficient treatment of a paraneoplastic neurological syndrome (PNS) a second neoplasia was suspected in the patient. By the aid of whole body positron emission tomography with 18-fluorine fluoro-2-deoxy-glucose (FDG-PET) an adenocarcinoma of the cecum could be detected. Two months after surgery anti-Ma antibodies were negative. We conclude that a second neoplasia should be considered, if effective cancer treatment does not lead to improvement or stabilisation of a PNS. Tumor search should be exhaustive and include PET when conventional imaging fails to show a malignancy.

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

    Science.gov (United States)

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

    2016-01-01

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

  15. Supratentorial white matter blurring associated with voltage-gated potassium channel-complex limbic encephalitis.

    Science.gov (United States)

    Urbach, H; Rauer, S; Mader, I; Paus, S; Wagner, J; Malter, M P; Prüss, H; Lewerenz, J; Kassubek, J; Hegen, H; Auer, M; Deisenhammer, F; Ufer, F; Bien, C G; Baumgartner, A

    2015-12-01

    Limbic encephalitis (LE) associated with voltage-gated potassium channel-complex antibodies (VGKC-LE) is frequently non-paraneoplastic and associated with marked improvement following corticosteroid therapy. Mesial temporal lobe abnormalities are present in around 80 % of patients. If associated or preceded by faciobrachial dystonic seizures, basal ganglia signal changes may occur. In some patients, blurring of the supratentorial white matter on T2-weighted images (SWMB) may be seen. The purpose of this study was to evaluate the incidence of SWMB and whether it is specific for VGKC-LE. Two experienced neuroradiologists independently evaluated signal abnormalities on FLAIR MRI in 79 patients with LE while unaware on the antibody type. SWMB was independently assessed as present in 10 of 36 (28 %) compared to 2 (5 %) of 43 non-VGKC patients (p = 0.009). It was not related to the presence of LGI1 or CASPR2 proteins of VGKC antibodies. MRI showed increased temporomesial FLAIR signal in 22 (61 %) VGKC compared to 14 (33 %) non-VGKC patients (p = 0.013), and extratemporomesial structures were affected in one VGKC (3 %) compared to 11 (26 %) non-VGKC patients (p = 0.005). SWMB is a newly described MRI sign rather specific for VGKC-LE.

  16. The teen brain: insights from neuroimaging.

    Science.gov (United States)

    Giedd, Jay N

    2008-04-01

    Few parents of a teenager are surprised to hear that the brain of a 16-year-old is different from the brain of an 8-year-old. Yet to pin down these differences in a rigorous scientific way has been elusive. Magnetic resonance imaging, with the capacity to provide exquisitely accurate quantifications of brain anatomy and physiology without the use of ionizing radiation, has launched a new era of adolescent neuroscience. Longitudinal studies of subjects from ages 3-30 years demonstrate a general pattern of childhood peaks of gray matter followed by adolescent declines, functional and structural increases in connectivity and integrative processing, and a changing balance between limbic/subcortical and frontal lobe functions, extending well into young adulthood. Although overinterpretation and premature application of neuroimaging findings for diagnostic purposes remains a risk, converging data from multiple imaging modalities is beginning to elucidate the implications of these brain changes on cognition, emotion, and behavior.

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

    Directory of Open Access Journals (Sweden)

    Chandra Mohan Sharma

    2016-01-01

    Full Text Available 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.

  18. Diffusion tensor tractography of the mammillothalamic tract in the human brain using a high spatial resolution DTI technique.

    Science.gov (United States)

    Kamali, Arash; Zhang, Caroline C; Riascos, Roy F; Tandon, Nitin; Bonafante-Mejia, Eliana E; Patel, Rajan; Lincoln, John A; Rabiei, Pejman; Ocasio, Laura; Younes, Kyan; Hasan, Khader M

    2018-03-27

    The mammillary bodies as part of the hypothalamic nuclei are in the central limbic circuitry of the human brain. The mammillary bodies are shown to be directly or indirectly connected to the amygdala, hippocampus, and thalami as the major gray matter structures of the human limbic system. Although it is not primarily considered as part of the human limbic system, the thalamus is shown to be involved in many limbic functions of the human brain. The major direct connection of the thalami with the hypothalamic nuclei is known to be through the mammillothalamic tract. Given the crucial role of the mammillothalamic tracts in memory functions, diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of this pathway noninvasively. This study aimed to investigate the utility of high spatial resolution diffusion tensor tractography for mapping the trajectory of the mammillothalamic tract in the human brain. Fifteen healthy adults were studied after obtaining written informed consent. We used high spatial resolution diffusion tensor imaging data at 3.0 T. We delineated, for the first time, the detailed trajectory of the mammillothalamic tract of the human brain using deterministic diffusion tensor tractography.

  19. The deep stimulation of the sub-thalamus nucleus affects the limbic and associative circuits: a study in {sup 18}F-F.D.G. -PET in the Parkinson disease;La stimulation profonde du noyau sous thalamique affecte les circuits limbique et associatif: une etude en 18FDG-TEP dans la maladie de Parkinson

    Energy Technology Data Exchange (ETDEWEB)

    Le Jeune, F.; Garin, E. [Centre Eugene-Marquis, Servive de medecine nucleaire, 35 - Rennes (France); Le Jeune, F.; Peron, J.; Grandjean, D.; Drapier, S.; Haegelen, C.; Garin, E.; Millet, B.; Verin, M. [Universite de Rennes-1, URU comportement et noyaux gris centraux, 35 - Rennes (France); Peron, J.; Drapier, S.; Haegelen, C.; Verin, M. [CHU Pontchaillou, service de neurologie, 35 - Rennes (France); Grandjean, D. [University of Genova, Swiss Center for Affective Sciences, Geneve (Switzerland); Millet, B. [Centre hospitalier Guillaume-Regnier, service de psychiatrie adulte, 35 - Rennes (France)

    2010-05-15

    The purpose of this study is to highlight the changes in brain metabolism in {sup 18}F.D.G.-PET to improve understanding of the non-motor functional role .This study confirms the non-motor functional role of the sub thalamic nucleus (S.T.N.) in limbic and associative circuits in humans.These results provide working hypotheses to study the correlations between neuropsychological alterations clinically diagnosed and cerebral metabolism in order to identify the neural circuits involved. (N.C.)

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

    OpenAIRE

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

    2014-01-01

    Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (~45 mmHg). Subjects rated dyspnea (air hunger) via visual analog scale...

  1. Radiofrequency attenuator and method

    Science.gov (United States)

    Warner, Benjamin P [Los Alamos, NM; McCleskey, T Mark [Los Alamos, NM; Burrell, Anthony K [Los Alamos, NM; Agrawal, Anoop [Tucson, AZ; Hall, Simon B [Palmerston North, NZ

    2009-01-20

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  2. Attenuation coefficients of soils

    International Nuclear Information System (INIS)

    Martini, E.; Naziry, M.J.

    1989-01-01

    As a prerequisite to the interpretation of gamma-spectrometric in situ measurements of activity concentrations of soil radionuclides the attenuation of 60 to 1332 keV gamma radiation by soil samples varying in water content and density has been investigated. A useful empirical equation could be set up to describe the dependence of the mass attenuation coefficient upon photon energy for soil with a mean water content of 10%, with the results comparing well with data in the literature. The mean density of soil in the GDR was estimated at 1.6 g/cm 3 . This value was used to derive the linear attenuation coefficients, their range of variation being 10%. 7 figs., 5 tabs. (author)

  3. Altered brain functional connectivity and behaviour in a mouse model of maternal alcohol binge-drinking.

    Science.gov (United States)

    Cantacorps, Lídia; González-Pardo, Héctor; Arias, Jorge L; Valverde, Olga; Conejo, Nélida M

    2018-06-08

    Prenatal and perinatal alcohol exposure caused by maternal alcohol intake during gestation and lactation periods can have long-lasting detrimental effects on the brain development and behaviour of offspring. Children diagnosed with Foetal Alcohol Spectrum Disorders (FASD) display a wide range of cognitive, emotional and motor deficits, together with characteristic morphological abnormalities. Maternal alcohol binge drinking is particularly harmful for foetal and early postnatal brain development, as it involves exposure to high levels of alcohol over short periods of time. However, little is known about the long-term effects of maternal alcohol binge drinking on brain function and behaviour. To address this issue, we used pregnant C57BL/6 female mice with time-limited access to a 20% v/v alcohol solution as a procedure to model alcohol binge drinking during gestation and lactational periods. Male offspring were behaviourally tested during adolescence (30 days) and adulthood (60 days), and baseline neural metabolic capacity of brain regions sensitive to alcohol effects were also evaluated in adult animals from both groups. Our results show that prenatal and postnatal alcohol exposure caused age-dependent changes in spontaneous locomotor activity, increased anxiety-like behaviour and attenuated alcohol-induced conditioned place preference in adults. Also, significant changes in neural metabolic capacity using cytochrome c oxidase (CCO) quantitative histochemistry were found in the hippocampal dentate gyrus, the mammillary bodies, the ventral tegmental area, the lateral habenula and the central lobules of the cerebellum in adult mice with prenatal and postnatal alcohol exposure. In addition, the analysis of interregional CCO activity correlations in alcohol-exposed adult mice showed disrupted functional brain connectivity involving the limbic, brainstem, and cerebellar regions. Finally, increased neurogenesis was found in the dentate gyrus of the hippocampus of

  4. Ghrelin modulates the fMRI BOLD response of homeostatic and hedonic brain centers regulating energy balance in the rat.

    Directory of Open Access Journals (Sweden)

    Miklós Sárvári

    Full Text Available The orexigenic gut-brain peptide, ghrelin and its G-protein coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1A are pivotal regulators of hypothalamic feeding centers and reward processing neuronal circuits of the brain. These systems operate in a cooperative manner and receive a wide array of neuronal hormone/transmitter messages and metabolic signals. Functional magnetic resonance imaging was employed in the current study to map BOLD responses to ghrelin in different brain regions with special reference on homeostatic and hedonic regulatory centers of energy balance. Experimental groups involved male, ovariectomized female and ovariectomized estradiol-replaced rats. Putative modulation of ghrelin signaling by endocannabinoids was also studied. Ghrelin-evoked effects were calculated as mean of the BOLD responses 30 minutes after administration. In the male rat, ghrelin evoked a slowly decreasing BOLD response in all studied regions of interest (ROI within the limbic system. This effect was antagonized by pretreatment with GHS-R1A antagonist JMV2959. The comparison of ghrelin effects in the presence or absence of JMV2959 in individual ROIs revealed significant changes in the prefrontal cortex, nucleus accumbens of the telencephalon, and also within hypothalamic centers like the lateral hypothalamus, ventromedial nucleus, paraventricular nucleus and suprachiasmatic nucleus. In the female rat, the ghrelin effects were almost identical to those observed in males. Ovariectomy and chronic estradiol replacement had no effect on the BOLD response. Inhibition of the endocannabinoid signaling by rimonabant significantly attenuated the response of the nucleus accumbens and septum. In summary, ghrelin can modulate hypothalamic and mesolimbic structures controlling energy balance in both sexes. The endocannabinoid signaling system contributes to the manifestation of ghrelin's BOLD effect in a region specific manner. In females, the

  5. Computer-controlled attenuator.

    Science.gov (United States)

    Mitov, D; Grozev, Z

    1991-01-01

    Various possibilities for applying electronic computer-controlled attenuators for the automation of physiological experiments are considered. A detailed description is given of the design of a 4-channel computer-controlled attenuator, in two of the channels of which the output signal can change by a linear step, in the other two channels--by a logarithmic step. This, together with the existence of additional programmable timers, allows to automate a wide range of studies in different spheres of physiology and psychophysics, including vision and hearing.

  6. Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects.

    Science.gov (United States)

    Hui, Kathleen K S; Marina, Ovidiu; Claunch, Joshua D; Nixon, Erika E; Fang, Jiliang; Liu, Jing; Li, Ming; Napadow, Vitaly; Vangel, Mark; Makris, Nikos; Chan, Suk-Tak; Kwong, Kenneth K; Rosen, Bruce R

    2009-09-01

    Previous work has shown that acupuncture stimulation evokes deactivation of a limbic-paralimbic-neocortical network (LPNN) as well as activation of somatosensory brain regions. This study explores the activity and functional connectivity of these regions during acupuncture vs. tactile stimulation and vs. acupuncture associated with inadvertent sharp pain. Acupuncture during 201 scans and tactile stimulation during 74 scans for comparison at acupoints LI4, ST36 and LV3 was monitored with fMRI and psychophysical response in 48 healthy subjects. Clusters of deactivated regions in the medial prefrontal, medial parietal and medial temporal lobes as well as activated regions in the sensorimotor and a few paralimbic structures can be identified during acupuncture by general linear model analysis and seed-based cross correlation analysis. Importantly, these clusters showed virtual identity with the default mode network and the anti-correlated task-positive network in response to stimulation. In addition, the amygdala and hypothalamus, structures not routinely reported in the default mode literature, were frequently involved in acupuncture. When acupuncture induced sharp pain, the deactivation was attenuated or became activated instead. Tactile stimulation induced greater activation of the somatosensory regions but less extensive deactivation of the LPNN. These results indicate that the deactivation of the LPNN during acupuncture cannot be completely explained by the demand of attention that is commonly proposed in the default mode literature. Our results suggest that acupuncture mobilizes the anti-correlated functional networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response.

  7. Trait anxiety modulates fronto-limbic processing of emotional interference in Borderline Personality Disorder

    Directory of Open Access Journals (Sweden)

    Jana eHoltmann

    2013-03-01

    Full Text Available 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 versus 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 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

  8. GAD antibody-associated limbic encephalitis in a young woman with APECED

    Directory of Open Access Journals (Sweden)

    Anna Kopczak

    2017-05-01

    Full Text Available The autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED syndrome is a genetic disorder caused by a mutation in the autoimmune regulator (AIRE gene. Immune deficiency, hypoparathyroidism and Addison’s disease due to autoimmune dysfunction are the major clinical signs of APECED. We report on a 21-year-old female APECED patient with two inactivating mutations in the AIRE gene. She presented with sudden onset of periodic nausea. Adrenal insufficiency was diagnosed by means of the ACTH stimulation test. Despite initiation of hormone replacement therapy with hydrocortisone and fludrocortisone, nausea persisted and the patient developed cognitive deficits and a loss of interest which led to the diagnosis of depression. She was admitted to the psychiatric department for further diagnostic assessment. An EEG showed a focal epileptic pattern. Glutamic acid decarboxylase (GAD antibodies, which had been negative eight years earlier, were now elevated in serum and in the cerebrospinal fluid. Oligoclonal bands were positive indicating an inflammatory process with intrathecal antibody production in the central nervous system (CNS. The periodic nausea was identified as dialeptic seizures, which clinically presented as gastrointestinal aura followed by episodes of reduced consciousness that occurred about 3–4 times per day. GAD antibody-associated limbic encephalitis (LE was diagnosed. Besides antiepileptic therapy, an immunosuppressive treatment with corticosteroids was initiated followed by azathioprine. The presence of nausea and vomiting in endocrine patients with autoimmune disorders is indicative of adrenal insufficiency. However, our case report shows that episodic nausea may be a symptom of epileptic seizures due to GAD antibodies-associated LE in patients with APECED.

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

    Science.gov (United States)

    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

  10. Limbic-Auditory Interactions of Tinnitus: An Evaluation Using Diffusion Tensor Imaging.

    Science.gov (United States)

    Gunbey, H P; Gunbey, E; Aslan, K; Bulut, T; Unal, A; Incesu, L

    2017-06-01

    Tinnitus is defined as an imaginary subjective perception in the absence of an external sound. Convergent evidence proposes that tinnitus perception includes auditory, attentional and emotional components. The aim of this study was to investigate the thalamic, auditory and limbic interactions associated with tinnitus-related distress by Diffusion Tensor Imaging (DTI). A total of 36 tinnitus patients, 20 healthy controls underwent an audiological examination, as well as a magnetic resonance imaging protocol including structural and DTI sequences. All participants completed the Tinnitus Handicap Inventory (THI) and Visual Analog Scales (VAS) related with tinnitus. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained for the auditory cortex (AC), inferior colliculus (IC), lateral lemniscus (LL), medial geniculate body (MGB), thalamic reticular nucleus (TRN), amygdala (AMG), hippocampus (HIP), parahippocampus (PHIP) and prefrontal cortex (PFC). In tinnitus patients the FA values of IC, MGB, TRN, AMG, HIP decreased and the ADC values of IC, MGB, TRN, AMG, PHIP increased significantly. The contralateral IC-LL and bilateral MGB FA values correlated negatively with hearing loss. A negative relation was found between the AMG-HIP FA values and THI and VAS scores. Bilateral ADC values of PHIP and PFC significantly correlated with the attention deficiency-VAS scores. In conclusion, this is the first DTI study to investigate the grey matter structures related to tinnitus perception and the significant correlation of FA and ADC with clinical parameters suggests that DTI can provide helpful information for tinnitus. Magnifying the microstructures in DTI can help evaluate the three faces of tinnitus nature: hearing, emotion and attention.

  11. Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder.

    Science.gov (United States)

    Voon, Valerie; Brezing, Christina; Gallea, Cecile; Hallett, Mark

    2011-11-01

    Conversion disorder (CD) is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that CD with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amygdala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Subjects performed either an internally or externally generated 2-button action selection task in a functional MRI study. Eleven CD patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula, and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system, which is both hypoactive and functionally disconnected from prefrontal top-down regulation. Copyright © 2011 Movement Disorder Society.

  12. Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder

    Science.gov (United States)

    Voon, V; Brezing, C; Gallea, C; Hallett, M

    2014-01-01

    Background Conversion disorder is characterized by unexplained neurological symptoms presumed related to psychological issues. The main hypotheses to explain conversion paralysis, characterized by a lack of movement, include impairments in either motor intention or disruption of motor execution, and further, that hyperactive self-monitoring, limbic processing or top-down regulation from higher order frontal regions may interfere with motor execution. We have recently shown that conversion disorder with positive abnormal or excessive motor symptoms was associated with greater amygdala activity to arousing stimuli along with greater functional connectivity between the amgydala and supplementary motor area. Here we studied patients with such symptoms focusing on motor initiation. Methods Subjects performed either an internally or externally generated two-button action selection task in a functional MRI study. Results Eleven conversion disorder patients without major depression and 11 age- and gender-matched normal volunteers were assessed. During both internally and externally generated movement, conversion disorder patients relative to normal volunteers had lower left supplementary motor area (SMA) (implicated in motor initiation) and higher right amygdala, left anterior insula and bilateral posterior cingulate activity (implicated in assigning emotional salience). These findings were confirmed in a subgroup analysis of patients with tremor symptoms. During internally versus externally generated action in CD patients, the left SMA had lower functional connectivity with bilateral dorsolateral prefrontal cortices. Conclusion We propose a theory in which previously mapped conversion motor representations may in an arousing context hijack the voluntary action selection system which is both hypoactive and functionally disconnected from prefrontal top-down regulation. PMID:21935985

  13. Human limbic encephalitis serum enhances hippocampal mossy fiber-CA3 pyramidal cell synaptic transmission.

    Science.gov (United States)

    Lalic, Tatjana; Pettingill, Philippa; Vincent, Angela; Capogna, Marco

    2011-01-01

    Limbic encephalitis (LE) is a central nervous system (CNS) disease characterized by subacute onset of memory loss and epileptic seizures. A well-recognized form of LE is associated with voltage-gated potassium channel complex antibodies (VGKC-Abs) in the patients' sera. We aimed to test the hypothesis that purified immunoglobulin G (IgG) from a VGKC-Ab LE serum would excite hippocampal CA3 pyramidal cells by reducing VGKC function at mossy-fiber (MF)-CA3 pyramidal cell synapses. We compared the effects of LE and healthy control IgG by whole-cell patch-clamp and extracellular recordings from CA3 pyramidal cells of rat hippocampal acute slices. We found that the LE IgG induced epileptiform activity at a population level, since synaptic stimulation elicited multiple population spikes extracellularly recorded in the CA3 area. Moreover, the LE IgG increased the rate of tonic firing and strengthened the MF-evoked synaptic responses. The synaptic failure of evoked excitatory postsynaptic currents (EPSCs) was significantly lower in the presence of the LE IgG compared to the control IgG. This suggests that the LE IgG increased the release probability on MF-CA3 pyramidal cell synapses compared to the control IgG. Interestingly, α-dendrotoxin (120 nm), a selective Kv1.1, 1.2, and 1.6 subunit antagonist of VGKC, mimicked the LE IgG-mediated effects. This is the first functional demonstration that LE IgGs reduce VGKC function at CNS synapses and increase cell excitability. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

  14. Outcome of limbic encephalitis with VGKC-complex antibodies: relation to antigenic specificity.

    Science.gov (United States)

    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.

  15. Natural attenuation of herbicides

    DEFF Research Database (Denmark)

    Tuxen, Nina; Højberg, Anker Lajer; Broholm, Mette Martina

    2002-01-01

    A field injection experiment in a sandy, aerobic aquifer showed that two phenoxy acids MCPP (mecoprop) and dichlorprop were degraded within I in downgradient of the injection wells after an apparent lag period. The plume development and microbial measurements indicated that microbial growth gover....... The observations may be important for application of natural attenuation as a remedy in field scale systems....

  16. The psychopath magnetized: insights from brain imaging

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

    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

  18. P300 is attenuated during dissociative episodes.

    Science.gov (United States)

    Kirino, Eiji

    2006-02-01

    The present study examined the pathophysiology of dissociative phenomena using the P300 component of event-related potentials, quantitative electroencephalography (QEEG), and morphology measures of computed tomography scan. Event-related potentials during an auditory oddball paradigm and QEEG in resting state were recorded. Patients exhibited attenuation of P300 amplitudes compared with controls during dissociative episodes, but exhibited recovery to control levels in remission. Patients had a larger Sylvian fissure-brain ratio than did controls. QEEG findings revealed no significant differences between the patients and controls or between episodes and remission in the patient group. Attenuation of the P300 can be interpreted as the result of a negative feedback loop from the medial temporal lobe to the cortex, which decreases the amount of information flow, allocation of attentional resources, and updating of working memory to avoid both excessive long-term memory system activity in medial temporal lobe and resurgence of affect-laden memories.

  19. Sex-specific impairment and recovery of spatial learning following the end of chronic unpredictable restraint stress: potential relevance of limbic GAD.

    Science.gov (United States)

    Ortiz, J Bryce; Taylor, Sara B; Hoffman, Ann N; Campbell, Alyssa N; Lucas, Louis R; Conrad, Cheryl D

    2015-04-01

    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 2 days and given one retention trial on the third day, with brains removed 30min 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Photon attenuation by intensifying screens

    International Nuclear Information System (INIS)

    Holje, G.

    1983-01-01

    The photon attenuation by intensifying screens of different chemical composition has been determined. The attenuation of photons between 20 keV and 120 keV was measured by use of a multi-channel analyzer and a broad bremsstrahlung distribution. The attenuation by the intensifying screens was hereby determined simultaneously at many different monoenergetic photon energies. Experimentally determined attenuations were found to agree well with attenuation calculated from mass attenuation coefficients. The attenuation by the screens was also determined at various bremsstrahlung distributions, simulating those occurring behind the patient in various diagnostic X-ray examinations. The high attenuation in some of the intensifying screens form the basis for an analysis of the construction of asymmetric screen pairs. Single screen systems are suggested as a favourable alternative to thick screen pair systems. (Author)

  1. Neuroticism and Functional Connectomics of the Resting Adolescent Brain

    DEFF Research Database (Denmark)

    Baruël Johansen, Louise

    The personality trait neuroticism is a well-known risk factor for anxiety and mood disorders that typically have their onset in childhood and adolescence. This period is characterized by ongoing structural and functional maturation of the brain, which can be traced with magnetic resonance imaging...... network organization on the global level, while network characteristics of fronto-limbic regions, involved in emotional processing, are implicated on a local level. Little is known about neuroticism and functional brain organization in childhood and adolescence. The main aim of this thesis was therefore...

  2. Autoradiographic localization of drug and neurotransmitter receptors in the brain

    International Nuclear Information System (INIS)

    Kuhar, M.J.

    1981-01-01

    By combining and adapting various methodologies, it is possible to develop radiohistochemical methods for the light microscopic localization of drug and neurotransmitter receptors in the brain. These methods are valuable complements to other histochemical methods for mapping neurotransmitters; they provide a unique view of neuroanatomy and they can be used to provide valuable new hypotheses about how drugs produce various effects. Interesting 'hot spots' of receptor localizations have been observed in some sensory and limbic areas of the brain. Because most available methods are light microscopic, the development of ultrastructural methods will be a necessary and important extension of this field. (Auth.)

  3. Enhanced Attenuation: Chlorinated Organics

    Science.gov (United States)

    2008-04-01

    attenuation capacity of the aquifer downgradient from the source (e.g., permeable reactive barriers or phytoremediation ) Selection of EA remedies should be...prevalence and/or mobility of nitrate and sulfate compounds and/or metals such as iron, manganese, chromium, copper, and arsenic . Furthermore, in...ranging from very aggressive source destruction and removal methods to less energy-intensive methods, such as phytoremediation . In many cases, it

  4. Control algorithms for dynamic attenuators

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Scott S., E-mail: sshsieh@stanford.edu [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Pelc, Norbert J. [Department of Radiology, Stanford University, Stanford California 94305 and Department of Bioengineering, Stanford University, Stanford, California 94305 (United States)

    2014-06-15

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  5. Control algorithms for dynamic attenuators

    International Nuclear Information System (INIS)

    Hsieh, Scott S.; Pelc, Norbert J.

    2014-01-01

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  6. Control algorithms for dynamic attenuators.

    Science.gov (United States)

    Hsieh, Scott S; Pelc, Norbert J

    2014-06-01

    The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current modulation) without

  7. Changes of brain structure in Parkinson's disease patients with mild cognitive impairment analyzed via VBM technology.

    Science.gov (United States)

    Gao, Yuyuan; Nie, Kun; Huang, Biao; Mei, Mingjin; Guo, Manli; Xie, Sifen; Huang, Zhiheng; Wang, Limin; Zhao, Jiehao; Zhang, Yuhu; Wang, Lijuan

    2017-09-29

    To analyze changes in cerebral grey matter volume and white matter density in non-dementia Parkinson's disease patients using voxel-based morphometry (VBM) technology; to investigate features of brain structure changes in Parkinson's disease patients with mild cognitive impairment (PD-MCI), and reveal their intrinsic pathological changes. Based on the diagnostic criteria of PD-MCI, 23 PD-MCI patients, 23 Parkinson's disease patients with normal cognition (PD-NC), and 21 age- and gender-matched healthy people were recruited for the study. Scans were performed on all subjects on a 3.0T MR scanner to obtain brain structural magnetic resonance images. Images were preprocessed using the VBM8 tool from SPM8 software package on the Matlab R2008a platform, and data were then analyzed using the SPM statistical software package to compare the differences of grey matter volume and white matter density between groups, and to evaluate the brain structural changes corresponding to the overall cognitive function. Compared to the control group, the PD-NC group suffered from grey matter atrophy, mainly found in the prefrontal lobe, limbic lobe and left temporal gyrus. The PD-MCI group suffered from grey matter atrophy found in the frontal lobe, limbic lobe, basal ganglia and cerebellum. Compared to the PD-NC group, the PD-MCI group suffered from grey matter atrophy found in the left-side middle temporal gyrus, inferior temporal gyrus and frontal lobe. The grey matter regions correlated with MMSE score (mainly memory related) including the right cingulate gyrus and the limbic lobe. The grey matter regions correlated with MoCA score (mainly non-memory related) including the frontal lobe, basal ganglia, parahippocampal gyrus, occipital lobe and the cerebellum. Additionally, overall cognitive function in non-dementia PD was mainly located in the frontal and limbic system, and was dominated by subcortical atrophy. Structural changes in PD-MCI patients are associated with overall

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

    Science.gov (United States)

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

    2018-04-16

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

  9. Tracking functional brain changes in patients with depression under psychodynamic psychotherapy using individualized stimuli.

    Directory of Open Access Journals (Sweden)

    Daniel Wiswede

    Full Text Available OBJECTIVE: Neurobiological models of depression posit limbic hyperactivity that should normalize after successful treatment. For psychotherapy, though, brain changes in patients with depression show substantial variability. Two critical issues in relevant studies concern the use of unspecific stimulation experiments and relatively short treatment protocols. Therefore changes in brain reactions to individualized stimuli were studied in patients with depression after eight months of psychodynamic psychotherapy. METHODS: 18 unmedicated patients with recurrent major depressive disorder were confronted with individualized and clinically derived content in a functional MRI experiment before (T1 and after eight months (T2 of psychodynamic therapy. A control group of 17 healthy subjects was also tested twice without intervention. The experimental stimuli were sentences describing each participant's dysfunctional interpersonal relationship patterns derived from clinical interviews based on Operationalized Psychodynamic Diagnostics (OPD. RESULTS: At T1 patients showed enhanced activation compared to controls in several limbic and subcortical regions, including amygdala and basal ganglia, when confronted with OPD sentences. At T2 the differences in brain activity between patients and controls were no longer apparent. Concurrently, patients had improved significantly in depression scores. CONCLUSIONS: Using ecologically valid stimuli, this study supports the model of limbic hyperactivity in depression that normalizes after treatment. Without a control group of untreated patients measured twice, though, changes in patients' brain activity could also be attributed to other factors than psychodynamic therapy.

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

    International Nuclear Information System (INIS)

    Miletich, R.S.

    1985-01-01

    The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and 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 α-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 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. 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

  11. Primary sleep disorders can cause long-term sleep disturbance in patients with autoimmune mediated limbic encephalitis.

    Science.gov (United States)

    Anderson, Kirstie N; Kelly, Thomas P; Griffiths, Timothy D

    2013-07-01

    Antibody mediated limbic encephalitis causes a sub acute encephalopathy with an amnestic syndrome, seizures and often an affective prodrome. Sleep disturbance including abnormal dream sleep and insomnia are described in a percentage of long-term survivors but there are very few detailed assessments of sleep disturbance in patients beyond the acute phase of illness. The objectives of this study were to understand the causes of sleep disturbance in the long-term survivors of antibody mediated limbic encephalitis. We screened twelve patients under long-term follow up with sleep questionnaires and went on to perform detailed sleep studies (polysomnography) in those who reported sleep disturbance. Two were found to have persistent, severe central and obstructive sleep apnoea and two others to have restless legs and periodic limb movements of sleep. This highlights the need to investigate sleep disturbance in this group of patients. Effective treatments may be available to improve quality of life and daytime function. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. The effects of exercise on cigarette cravings and brain activation in response to smoking-related images.

    Science.gov (United States)

    Janse Van Rensburg, Kate; Taylor, Adrian; Benattayallah, Abdelmalek; Hodgson, Tim

    2012-06-01

    Smokers show heightened activation toward smoking-related stimuli and experience increased cravings which can precipitate smoking cessation relapse. Exercise can be effective for modulating cigarette cravings and attenuating reactivity to smoking cues, but the mechanism by which these effects occur remains uncertain. The objective of the study was to assess the effect of exercise on regional brain activation in response to smoking-related images during temporary nicotine abstinence. In a randomised crossover design, overnight abstinent smokers (n = 20) underwent an exercise (10-min moderate-intensity stationary cycling) and passive control (seating for the same duration) treatment, following 15 h of nicotine abstinence. After each treatment, participants underwent functional magnetic resonance imaging (fMRI) brain scanning while viewing a random series of blocked smoking or neutral images. Self-reported cravings were assessed at baseline, mid-, and post-treatments. There was a significant interaction effect (treatment × time) for desire to smoke, F (2,32) = 12.5, p exercise at all time points compared with the control treatment. After both exercise and rest, significant areas of activation were found in areas of the limbic lobe and in areas associated with visual attention in response to smoking-related stimuli. Smokers showed increased activation to smoking images in areas associated with primary and secondary visual processing following rest, but not following a session of exercise. The study shows differing activation towards smoking images following exercise compared to a control treatment and may point to a neuro-cognitive process following exercise that mediates effects on cigarette cravings.

  13. Male-to-female transsexuals have female neuron numbers in a limbic nucleus

    NARCIS (Netherlands)

    Kruijver, F. P.; Zhou, J. N.; Pool, C. W.; Hofman, M. A.; Gooren, L. J.; Swaab, D. F.

    2000-01-01

    Transsexuals experience themselves as being of the opposite sex, despite having the biological characteristics of one sex. A crucial question resulting from a previous brain study in male-to-female transsexuals was whether the reported difference according to gender identity in the central part of

  14. A fully automated and reproducible level-set segmentation approach for generation of MR-based attenuation correction map of PET images in the brain employing single STE-MR imaging modality

    Energy Technology Data Exchange (ETDEWEB)

    Kazerooni, Anahita Fathi; Aarabi, Mohammad Hadi [Quantitative MR Imaging and Spectroscopy Group, Research Center for Cellular and Molecular Imaging, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ay, Mohammadreza [Quantitative MR Imaging and Spectroscopy Group, Research Center for Cellular and Molecular Imaging, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Medical Imaging Systems Group, Research Center for Cellular and Molecular Imaging, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Rad, Hamidreza Saligheh [Quantitative MR Imaging and Spectroscopy Group, Research Center for Cellular and Molecular Imaging, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2014-07-29

    Generating MR-based attenuation correction map (μ-map) for quantitative reconstruction of PET images still remains a challenge in hybrid PET/MRI systems, mainly because cortical bone structures are indistinguishable from proximal air cavities in conventional MR images. Recently, development of short echo-time (STE) MR imaging sequences, has shown promise in differentiating cortical bone from air. However, on STE-MR images, the bone appears with discontinuous boundaries. Therefore, segmentation techniques based on intensity classification, such as thresholding or fuzzy C-means, fail to homogeneously delineate bone boundaries, especially in the presence of intrinsic noise and intensity inhomogeneity. Consequently, they cannot be fully automatized, must be fine-tuned on the case-by-case basis, and require additional morphological operations for segmentation refinement. To overcome the mentioned problems, in this study, we introduce a new fully automatic and reproducible STE-MR segmentation approach exploiting level-set in a clustering-based intensity inhomogeneity correction framework to reliably delineate bone from soft tissue and air.

  15. A fully automated and reproducible level-set segmentation approach for generation of MR-based attenuation correction map of PET images in the brain employing single STE-MR imaging modality

    International Nuclear Information System (INIS)

    Kazerooni, Anahita Fathi; Aarabi, Mohammad Hadi; Ay, Mohammadreza; Rad, Hamidreza Saligheh

    2014-01-01

    Generating MR-based attenuation correction map (μ-map) for quantitative reconstruction of PET images still remains a challenge in hybrid PET/MRI systems, mainly because cortical bone structures are indistinguishable from proximal air cavities in conventional MR images. Recently, development of short echo-time (STE) MR imaging sequences, has shown promise in differentiating cortical bone from air. However, on STE-MR images, the bone appears with discontinuous boundaries. Therefore, segmentation techniques based on intensity classification, such as thresholding or fuzzy C-means, fail to homogeneously delineate bone boundaries, especially in the presence of intrinsic noise and intensity inhomogeneity. Consequently, they cannot be fully automatized, must be fine-tuned on the case-by-case basis, and require additional morphological operations for segmentation refinement. To overcome the mentioned problems, in this study, we introduce a new fully automatic and reproducible STE-MR segmentation approach exploiting level-set in a clustering-based intensity inhomogeneity correction framework to reliably delineate bone from soft tissue and air.

  16. Brain activity and connectivity during poetry composition: Toward a multidimensional model of the creative process.

    Science.gov (United States)

    Liu, Siyuan; Erkkinen, Michael G; Healey, Meghan L; Xu, Yisheng; Swett, Katherine E; Chow, Ho Ming; Braun, Allen R

    2015-09-01

    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. © 2015 Wiley Periodicals, Inc.

  17. Induction of Innate Immune Genes in Brain Create the Neurobiology of Addiction

    OpenAIRE

    Crews, FT; Zou, Jian; Qin, Liya

    2011-01-01

    Addiction occurs through repeated abuse of drugs that progressively reduce behavioral control and cognitive flexibility while increasing limbic negative emotion. Recent discoveries indicate neuroimmune signaling underlies addiction and co-morbid depression. Low threshold microglia undergo progressive stages of innate immune activation involving astrocytes and neurons with repeated drug abuse, stress, and/or cell damage signals. Increased brain NF-κB transcription of proinflammatory chemokines...

  18. Captopril and Valsartan May Improve Cogniti ve Function Through Potentiation of the Brain Antioxidant Defense System and Attenuation of Oxidative/Nitrosative Damage in STZ - Induced Dementia in Rat

    Directory of Open Access Journals (Sweden)

    Yasaman Arjmand Abbassi

    2016-12-01

    Full Text Available Purpose: Previous findings have shown the crucial roles of brain renin-angiotensin system (RAS in pathogenesis of Alzheimer’s disease (AD. Since RAS inhibitors may have beneficial effects on dementia and cognitive function in elderly people, the aim of present study was to examine the neuroprotective actions of captopril and valsartan on memory function and neuronal damage in experimental model of AD. Methods: Adult forty male Wistar rats (220-280g were randomly divided into 5 groups; Control, Vehicle, Alzheimer and treatment groups. AD was induced by the injections of streptozotocin (3mg/kg, bilateral intracerebroventricular at days 1&3. Treated rats received orally captopril (50mg/kg/day and valsartan (30mg/kg/day. Memory function and histological assessments were done at termination of experiment. Finally, superoxide dismutase (SOD and catalase (CAT activities as well as malondialdehyde (MDA and NOx contents were determined. Results: There was a significant increase in the mean value of latency in Alzheimer group (66%. Captopril and valsartan considerably decreased this value in both treatment groups (45% and 72%, respectively. In Alzheimer group the activities of brain’s SOD and CAT reduced (40% and 47%, respectively in accompany with an increase in MDA and NOx contents (49% and 50%, respectively. Captopril and valsartan significantly increased the activities of brain’s SOD and CAT concomitant reduction in MDA and NOx contents. Also, histopathological damages noticeably decreased in both treatment groups. Conclusion: Our findings indicate that RAS inhibition by using captopril and valsartan potentiates the antioxidant defense system of brain and reduces oxidative/nitrosative stress in accompany with neuronal damage during AD.

  19. Limbic encephalitis associated with anti-NH2-terminal of α-enolase antibodies: A clinical subtype of Hashimoto encephalopathy.

    Science.gov (United States)

    Kishitani, Toru; Matsunaga, Akiko; Ikawa, Masamichi; Hayashi, Kouji; Yamamura, Osamu; Hamano, Tadanori; Watanabe, Osamu; Tanaka, Keiko; Nakamoto, Yasunari; Yoneda, Makoto

    2017-03-01

    Several types of autoantibodies have been reported in autoimmune limbic encephalitis (LE), such as antibodies against the voltage-gated potassium channel (VGKC) complex including leucine-rich glioma inactivated 1 (LGI1). We recently reported a patient with autoimmune LE and serum anti-NH2-terminal of α-enolase (NAE) antibodies, a specific diagnostic marker for Hashimoto encephalopathy (HE), who was diagnosed with HE based on the presence of antithyroid antibodies and responsiveness to immunotherapy. This case suggests that LE patients with antibodies to both the thyroid and NAE could be diagnosed with HE and respond to immunotherapy. The aim of this study was to clarify the clinicoimmunological features and efficacy of immunotherapy in LE associated with anti-NAE antibodies to determine whether the LE is a clinical subtype of HE.We examined serum anti-NAE antibodies in 78 LE patients with limbic abnormality on magnetic resonance imaging and suspected HE based on positivity for antithyroid antibodies. Nineteen of the 78 patients had anti-NAE antibodies; however, 5 were excluded because they were double positive for antibodies to the VGKC complex including LGI1. No antibodies against the N-methyl-D-aspartate receptor (NMDAR), contactin-associated protein 2 (Caspr2), γ-aminobutyric acid-B receptor (GABABR), or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) were detected in the 19 patients. Among the remaining 14 who were positive only for anti-NAE antibodies, the median age was 62.5 (20-83) years, 9 (64%) were women, and 8 (57%) showed acute onset, with less than 2 weeks between onset and admission. Consciousness disturbance (71%) and memory disturbance (64%) were frequently observed, followed by psychiatric symptoms (50%) and seizures (43%). The frequency of these symptoms significantly differed between the acute- and subacute-onset groups. Abnormalities in cerebrospinal fluid and electroencephalogram were commonly observed (92% for both

  20. Structural covariance of neostriatal and limbic regions in patients with obsessive-compulsive disorder.

    Science.gov (United States)

    Subirà, Marta; Cano, Marta; de Wit, Stella J; Alonso, Pino; Cardoner, Narcís; Hoexter, Marcelo Q; Kwon, Jun Soo; Nakamae, Takashi; Lochner, Christine; Sato, João R; Jung, Wi Hoon; Narumoto, Jin; Stein, Dan J; Pujol, Jesus; Mataix-Cols, David; Veltman, Dick J; Menchón, José M; van den Heuvel, Odile A; Soriano-Mas, Carles

    2016-03-01

    Frontostriatal and frontoamygdalar connectivity alterations in patients with obsessive-compulsive disorder (OCD) have been typically described in functional neuroimaging studies. However, structural covariance, or volumetric correlations across distant brain regions, also provides network-level information. Altered structural covariance has been described in patients with different psychiatric disorders, including OCD, but to our knowledge, alterations within frontostriatal and frontoamygdalar circuits have not been explored. We performed a mega-analysis pooling structural MRI scans from the Obsessive-compulsive Brain Imaging Consortium and assessed whole-brain voxel-wise structural covariance of 4 striatal regions (dorsal and ventral caudate nucleus, and dorsal-caudal and ventral-rostral putamen) and 2 amygdalar nuclei (basolateral and centromedial-superficial). Images were preprocessed with the standard pipeline of voxel-based morphometry studies using Statistical Parametric Mapping software. Our analyses involved 329 patients with OCD and 316 healthy controls. Patients showed increased structural covariance between the left ventral-rostral putamen and the left inferior frontal gyrus/frontal operculum region. This finding had a significant interaction with age; the association held only in the subgroup of older participants. Patients with OCD also showed increased structural covariance between the right centromedial-superficial amygdala and the ventromedial prefrontal cortex. This was a cross-sectional study. Because this is a multisite data set analysis, participant recruitment and image acquisition were performed in different centres. Most patients were taking medication, and treatment protocols differed across centres. Our results provide evidence for structural network-level alterations in patients with OCD involving 2 frontosubcortical circuits of relevance for the disorder and indicate that structural covariance contributes to fully characterizing brain

  1. Mapping the trajectory of the amygdalothalamic tract in the human brain.

    Science.gov (United States)

    Kamali, Arash; Riascos, Roy F; Pillai, Jay J; Sair, Haris I; Patel, Rajan; Nelson, Flavia M; Lincoln, John A; Tandon, Nitin; Mirbagheri, Saeedeh; Rabiei, Pejman; Keser, Zafer; Hasan, Khader M

    2018-04-01

    Although the thalamus is not considered primarily as a limbic structure, abundant evidence indicates the essential role of the thalamus as a modulator of limbic functions indirectly through the amygdala. The amygdala is a central component of the limbic system and serves an essential role in modulating the core processes including the memory, decision-making, and emotional reactions. The amygdalothalamic pathway is the largest direct amygdalo-diencephalic connection in the primates including the human brain. Given the crucial role of the amygdalothalamic tract (ATT) in memory function and diencephalic amnesia in stroke patients, diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of this pathway noninvasively. To date, few diffusion-weighted studies have focused on the amygdala, yet the fine neuronal connection of the amygdala and thalamus known as the ATT has yet to be elucidated. This study aimed to investigate the utility of high spatial resolution diffusion tensor tractography for mapping the trajectory of the ATT in the human brain. We studied 15 healthy right-handed human subjects (12 men and 3 women with age range of 24-37 years old). Using a high-resolution diffusion tensor tractography technique, for the first time, we were able to reconstruct and measure the trajectory of the ATT. We further revealed the close relationship of the ATT with the temporopontine tract and the fornix bilaterally in 15 healthy adult human brains. © 2018 Wiley Periodicals, Inc.

  2. The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls.

    Science.gov (United States)

    Soeiro-de-Souza, Márcio Gerhardt; Otaduy, Maria Concepción Garcia; Dias, Carolina Zadres; Bio, Danielle S; Machado-Vieira, Rodrigo; Moreno, Ricardo Alberto

    2012-12-01

    Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the α1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function. The aim of this study was to investigate the impact of CACNA1C genotype on FER scores and limbic system morphology in subjects with BD and healthy controls. Thirty-nine euthymic BD I subjects and 40 healthy controls were submitted to a FER recognition test battery and genotyped for CACNA1C. Subjects were also examined with a 3D 3-Tesla structural imaging protocol. The CACNA1C risk allele for BD was associated to FER impairment in BD, while in controls nothing was observed. The CACNA1C genotype did not impact on amygdala or hippocampus volume neither in BD nor controls. Sample size. The present findings suggest that a polymorphism in calcium channels interferes FER phenotype exclusively in BD and doesn't interfere on limbic structures morphology. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Increased limbic phosphorylated extracellular-regulated kinase 1 and 2 expression after chronic stress is reduced by cyclic 17 beta-estradiol administration

    NARCIS (Netherlands)

    Gerrits, M.; Westenbroek, C.; Koch, T.; Grootkarzijn, A.; Ter Horst, G. J.

    2006-01-01

    Chronic stress induced neuronal changes that may have consequences for subsequent stress responses. For example, chronic stress in rats rearranges dendritic branching patterns and disturbs the phosphorylation of extracellular-regulated kinase 1 and 2 (ERK) 1/2 throughout the limbic system.

  4. Persistent anterograde amnesia following limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex.

    Science.gov (United States)

    Butler, Christopher R; Miller, Thomas D; Kaur, Manveer S; Baker, Ian W; Boothroyd, Georgie D; Illman, Nathan A; Rosenthal, Clive R; Vincent, Angela; Buckley, Camilla J

    2014-04-01

    Limbic encephalitis (LE) associated with antibodies to the voltage-gated potassium channel complex (VGKC) is a potentially reversible cause of cognitive impairment. Despite the prominence of cognitive dysfunction in this syndrome, little is known about patients' neuropsychological profile at presentation or their long-term cognitive outcome. We used a comprehensive neuropsychological test battery to evaluate cognitive function longitudinally in 19 patients with VGKC-LE. Before immunotherapy, the group had significant impairment of memory, processing speed and executive function, whereas language and perceptual organisation were intact. At follow-up, cognitive impairment was restricted to the memory domain, with processing speed and executive function having returned to the normal range. Residual memory function was predicted by the antibody titre at presentation. The results show that, despite broad cognitive dysfunction in the acute phase, patients with VGKC-LE often make a substantial recovery with immunotherapy but may be left with permanent anterograde amnesia.

  5. Reversible dementia: two nursing home patients with voltage-gated potassium channel antibody-associated limbic encephalitis.

    Science.gov (United States)

    Reintjes, Wesley; Romijn, Marloes D M; Hollander, Daan; Ter Bruggen, Jan P; van Marum, Rob J

    2015-09-01

    Voltage-gated potassium channel antibody-associated limbic encephalitis (VGKC-LE) is a rare disease that is a diagnostic and therapeutic challenge for medical practitioners. Two patients with VGKC-LE, both developing dementia are presented. Following treatment, both patients showed remarkable cognitive and functional improvement enabling them to leave the psychogeriatric nursing homes they both were admitted to. Patients with VGKC-LE can have a major cognitive and functional improvement even after a diagnostic delay of more than 1 year. Medical practitioners who treat patients with unexplained cognitive decline, epileptic seizures, or psychiatric symptoms should be aware of LE as an underlying rare cause. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    Science.gov (United States)

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

    2017-03-01

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

  8. Suspected limbic encephalitis and seizure in cats associated with voltage-gated potassium channel (VGKC) complex antibody.

    Science.gov (United States)

    Pakozdy, A; Halasz, P; Klang, A; Bauer, J; Leschnik, M; Tichy, A; Thalhammer, J G; Lang, B; Vincent, A

    2013-01-01

    Treatment-resistant complex partial seizures (CPS) with orofacial involvement recently were reported in cats in association with hippocampal pathology. The features had some similarity to those described in humans with limbic encephalitis and voltage-gated potassium channel (VGKC) complex antibody. The purpose of this pilot study was to evaluate cats with CPS and orofacial involvement for the presence of VGKC-complex antibody. Client-owned cats with acute orofacial CPS and control cats were investigated. Prospective study. Serum was collected from 14 cats in the acute stage of the disease and compared with 19 controls. VGKC-complex antibodies were determined by routine immunoprecipitation and by binding to leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2), the 2 main targets of VGKC-complex antibodies in humans. Five of the 14 affected cats, but none of the 19 controls, had VGKC-complex antibody concentrations above the cut-off concentration (>100 pmol/L) based on control samples and similar to those found in humans. Antibodies in 4 cats were directed against LGI1, and none were directed against CASPR2. Follow-up sera were available for 5 cats in remission and all antibody concentrations were within the reference range. Our study suggests that an autoimmune limbic encephalitis exists in cats and that VGKC-complex/LGI1 antibodies may play a role in this disorder, as they are thought to in humans. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  9. Ultrasonic attenuation in superconducting zinc

    International Nuclear Information System (INIS)

    Auluck, S.

    1978-01-01

    The differences in the Zn ultrasonic attenuation data of different workers are analyzed. The superconducting energy gaps deduced from our analysis of the ultrasonic-attenuation data of Cleavelin and Marshall are consistent with the gaps deduced from the knowledge of the Fermi surface and the electron-phonon mass enhancement factor

  10. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

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

    Science.gov (United States)

    Morello, Noemi; Plicato, Ornella; Piludu, Maria Antonietta; Poddighe, Laura; Serra, Maria Pina; Quartu, Marina; Corda, Maria Giuseppa; Giorgi, Osvaldo; Giustetto, Maurizio

    2017-01-01

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

  12. Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock-induced acute lung injury through inhibiting oxidative stress and the NF-κB-dependent inflammatory/MMP-9 pathway.

    Science.gov (United States)

    Song, Zhi; Zhao, Xiu; Liu, Martin; Jin, Hongxu; Wang, Ling; Hou, Mingxiao; Gao, Yan

    2015-12-01

    Acute lung injury (ALI) is one of the most serious complications in traumatic patients and is an important part of multiple organ dysfunction syndrome (MODS). Recombinant human brain natriuretic peptide (rhBNP) is a peptide with a wide range of biological activity. In this study, we investigated local changes in oxidative stress and the NF-κB-dependent matrix metalloproteinase-9 (MMP-9) pathway in rats with trauma/haemorrhagic shock (TH/S)-induced ALI and evaluated the effects of pretreatment with rhBNP. Forty-eight rats were randomly divided into four groups: sham operation group, model group, low-dosage rhBNP group and high-dosage rhBNP group (n = 12 for each group). Oxidative stress and MPO activity were measured by ELISA kits. MMP-9 activity was detected by zymography analysis. NF-κB activity was determined using Western blot assay. With rhBNP pretreatment, TH/S-induced protein leakage, increased MPO activity, lipid peroxidation and metalloproteinase (MMP)-9 activity were inhibited. Activation of antioxidative enzymes was reversed. The phosphorylation of NF-κB and the degradation of its inhibitor IκB were suppressed. The results suggested that the protection mechanism of rhBNP is possibly mediated through upregulation of anti-oxidative enzymes and inhibition of NF-κB activation. More studies are needed to further evaluate whether rhBNP is a suitable candidate as an effective inhaling drug to reduce the incidence of TH/S-induced ALI. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

  13. Lutein and Brain Function

    Directory of Open Access Journals (Sweden)

    John W. Erdman

    2015-10-01

    Full Text Available Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated as macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Recently, interest in lutein has expanded beyond the retina to its possible contributions to brain development and function. Only primates accumulate lutein within the brain, but little is known about its distribution or physiological role. Our team has begun to utilize the rhesus macaque (Macaca mulatta model to study the uptake and bio-localization of lutein in the brain. Our overall goal has been to assess the association of lutein localization with brain function. In this review, we will first cover the evolution of the non-human primate model for lutein and brain studies, discuss prior association studies of lutein with retina and brain function, and review approaches that can be used to localize brain lutein. We also describe our approach to the biosynthesis of 13C-lutein, which will allow investigation of lutein flux, localization, metabolism and pharmacokinetics. Lastly, we describe potential future research opportunities.

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

    Science.gov (United States)

    Idris, Zamzuri

    2014-07-01

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

  15. Increased thalamic perfusion as a characteristic finding with brain SPECT in patients with obsessive-compulsive disorder

    International Nuclear Information System (INIS)

    Mut, F.; Beretta, M.; Nunez, M.; Zamora, R.

    2002-01-01

    Aim: Obsessive-compulsive disorder (OCD) is a relatively frequent psychiatric condition affecting most commonly young patients. Correct diagnosis and follow-up is essential in order to apply effective therapy. However, some common characteristics have been reported with brain SPECT for OCD and depression, with several brain structures belonging to the limbic system involved in both conditions: frontal cortex, cingulate gyrus, caudate nucleus, thalamus and hippocampus, among others. The aim of this study was to investigate quantitative findings of brain SPECT in OCD compared to other psychiatric conditions such as depression and dementia. Material and Methods: We studied 33 patients, 22 women, ages 39.3±10.9 years. Fifteen patients had clinical diagnosis of OCD (8 women, 21∫8 ys.), 13 of bipolar or unipolar depression (11 women, 28±15 ys.) and 5 of senile dementia (3 women, 69±10 ys). All were injected in the basal state with a standard dose of 925 MBq (25 mCi) of 99mTc-ECD. Brain SPECT was performed with a dual-head camera equipped with a high-resolution collimator using 360 0 rotation, 120 angular steps and 15 sec/step in a 64x64 matrix with 1.5 x magnification. Reconstruction of transaxial tomograms was performed using filtered backprojection with a Metz filter. Attenuation correction was applied according to Chang's method. In order to calculate uptake ratios, regions of interest (ROIs) were placed on the right and left frontal cortex (RFron, LFron), anterior or posterior cingulate gyrus (Cing) according to the site of highest uptake recorded, both caudate nucleus (RCau, LCau), thalamus (Thal) and cerebellum (cer). Results: The findings are presented. Conclusion: Cingulate gyrus hyperactivity has been reported in patients with OCD and confirmed in our series, however not significantly different from that observed in depressed patients. The only distinct finding was higher thalamic activity in OCD patients compared to the other groups, suggesting that this

  16. Melanocortin-3 receptors in the limbic system mediate feeding-related motivational responses during weight loss

    Directory of Open Access Journals (Sweden)

    Maria Mavrikaki

    2016-07-01

    Full Text Available Objective: Appetitive responses to weight loss are mediated by a nutrient-sensing neural network comprised of melanocortin neurons. The role of neural melanocortin-3 receptors (MC3R in mediating these responses is enigmatic. Mc3r knockout mice exhibit a paradoxical phenotype of obesity and reduced feeding-related behaviors in situations of nutrient scarcity. Here we examined whether MC3Rs expressed in mesolimbic neurons regulate feeding-related motivational responses. Methods: Interactions between Mc3r genotype, cognitive function and energy balance on food self-administration were assessed using operant conditioning with fixed- and progressive ratio (FR1/PR1 settings. Inhibition of Mc3r transcription by a loxP-flanked transcriptional blocker (TB in C57BL/6JN mice (Mc3rTB/TB was reversed in mesolimbic neurons using DAT-Cre (DAT-MC3R. Results: Caloric restriction (CR caused 10–15% weight loss and increased motivation to acquire food rewards during training sessions. c-Fos-expression in the nucleus accumbens was increased 1 h following food presentation. While exhibiting weight loss, total food self-administration, enhanced motivation to self-administer food rewards in training sessions held during CR and c-Fos-activation in the nucleus accumbens following re-feeding were all markedly attenuated in Mc3rTB/TB mice. In contrast, cognitive abilities were normal in Mc3rTB/TB mice. Total food self-administration during FR1 sessions was not rescued in DAT-MC3R mice, however enhanced motivational responses to self-administer food rewards in PR1 conditions were restored. The nutrient-partitioning phenotype observed with Mc3r-deficiency was not rescued in DAT-MC3R mice. Conclusions: Mesolimbic MC3Rs mediate enhanced motivational responses during CR. However, they are insufficient to restore normal caloric loading when food is presented during CR and do not affect metabolic conditions altering nutrient partitioning. Author Video: Author Video Watch what

  17. Nicotine increases brain functional network efficiency.

    Science.gov (United States)

    Wylie, Korey P; Rojas, Donald C; Tanabe, Jody; Martin, Laura F; Tregellas, Jason R

    2012-10-15

    Despite the use of cholinergic therapies in Alzheimer's disease and the development of cholinergic strategies for schizophrenia, relatively little is known about how the system modulates the connectivity and structure of large-scale brain networks. To better understand how nicotinic cholinergic systems alter these networks, this study examined the effects of nicotine on measures of whole-brain network communication efficiency. Resting state fMRI was acquired from fifteen healthy subjects before and after the application of nicotine or placebo transdermal patches in a single blind, crossover design. Data, which were previously examined for default network activity, were analyzed with network topology techniques to measure changes in the communication efficiency of whole-brain networks. Nicotine significantly increased local efficiency, a parameter that estimates the network's tolerance to local errors in communication. Nicotine also significantly enhanced the regional efficiency of limbic and paralimbic areas of the brain, areas which are especially altered in diseases such as Alzheimer's disease and schizophrenia. These changes in network topology may be one mechanism by which cholinergic therapies improve brain function. Published by Elsevier Inc.

  18. Electro-acupuncture at different acupoints modulating the relative specific brain functional network

    Science.gov (United States)

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

    2010-11-01

    Objective: The specific brain effects of acupoint are important scientific concern in acupuncture. However, previous acupuncture fMRI studies focused on acupoints in muscle layer on the limb. Therefore, researches on acupoints within connective tissue at trunk are warranted. Material and Methods: Brain effects of acupuncture on abdomen at acupoints Guanyuan (CV4) and Zhongwan (CV12) were tested using fMRI on 21 healthy volunteers. The data acquisition was performed at resting state, during needle retention, electroacupuncture (EA) and post-EA resting state. Needling sensations were rated after every electroacupuncture (EA) procedure. The needling sensations and the brain functional activity and connectivity were compared between CV4 and CV12 using SPSS, SPM2 and the local and remote connectivity maps. Results and conclusion: EA at CV4 and CV12 induced apparent deactivation effects in the limbic-paralimbic-neocortical network. The default mode of the brain was modified by needle retention and EA, respectively. The functional brain network was significantly changed post EA. However, the minor differences existed between these two acupoints. The results demonstrated similarity between functional brain network mode of acupuncture modulation and functional circuits of emotional and cognitive regulation. Acupuncture may produce analgesia, anti-anxiety and anti-depression via the limbic-paralimbic-neocortical network (LPNN).

  19. Limbic and Basal Ganglia Neuroanatomical Correlates of Gait and Executive Function: Older Adults With Mild Cognitive Impairment and Intact Cognition.

    Science.gov (United States)

    McGough, Ellen L; Kelly, Valerie E; Weaver, Kurt E; Logsdon, Rebecca G; McCurry, Susan M; Pike, Kenneth C; Grabowski, Thomas J; Teri, Linda

    2018-04-01

    This study aimed to examine differences in spatiotemporal gait parameters between older adults with amnestic mild cognitive impairment and normal cognition and to examine limbic