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Sample records for abnormal brain activity

  1. Maternal immune activation and abnormal brain development across CNS disorders.

    PubMed

    Knuesel, Irene; Chicha, Laurie; Britschgi, Markus; Schobel, Scott A; Bodmer, Michael; Hellings, Jessica A; Toovey, Stephen; Prinssen, Eric P

    2014-11-01

    Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. Such diversity of phenotypic outcomes in the mIA model are mirrored by recent clinical evidence suggesting that infectious exposure during pregnancy is also associated with epilepsy and, to a lesser extent, cerebral palsy in children. Preclinical research also suggests that mIA might precipitate the development of Alzheimer and Parkinson diseases. Here, we summarize and critically review the emerging evidence that mIA is a shared environmental risk factor across CNS disorders that varies as a function of interactions between genetic and additional environmental factors. We also review ongoing clinical trials targeting immune pathways affected by mIA that may play a part in disease manifestation. In addition, future directions and outstanding questions are discussed, including potential symptomatic, disease-modifying and preventive treatment strategies. PMID:25311587

  2. The MEG topography and the source model of abnormal neural activities associated with brain lesions

    SciTech Connect

    Ueno, S.; Iramina, K.; Ozaki, H.; Harada, K.

    1986-09-01

    A source model is proposed to simulate spatial distributions of abnormal MEG and EEG activities generated by abnormal neural activities such as the delta activity associated with brain tumors. Brain tumor itself is electrically silent and the spherical shell around the tumor might generate abnormal neural activities. The sources of these neural activities are represented by combinations of multiple current dipoles. The head is assumed to be a spherical volume conductor. Electrical potentials and magnetic fields over the surface of the spheres are calculated. The computer simulation shows that the MEG topography and EEG topography vary variously with combinations of location and orientation of the dipoles. In a special case, however, that the dipoles orient in the same direction or orient radially, the spatial patterns of the MEGs and EEGs generated by numerous dipoles are analogous to those generated by single dipoles.

  3. Abnormal brain activation during directed forgetting of negative memory in depressed patients.

    PubMed

    Yang, Wenjing; Chen, Qunlin; Liu, Peiduo; Cheng, Hongsheng; Cui, Qian; Wei, Dongtao; Zhang, Qinglin; Qiu, Jiang

    2016-01-15

    The frequent occurrence of uncontrollable negative thoughts and memories is a troubling aspect of depression. Thus, knowledge on the mechanism underlying intentional forgetting of these thoughts and memories is crucial to develop an effective emotion regulation strategy for depressed individuals. Behavioral studies have demonstrated that depressed participants cannot intentionally forget negative memories. However, the neural mechanism underlying this process remains unclear. In this study, participants completed the directed forgetting task in which they were instructed to remember or forget neutral or negative words. Standard univariate analysis based on the General Linear Model showed that the depressed participants have higher activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), superior parietal gyrus (SPG), and inferior temporal gyrus (ITG) than the healthy individuals. The results indicated that depressed participants recruited more frontal and parietal inhibitory control resources to inhibit the TBF items, but the attempt still failed because of negative bias. We also used the Support Vector Machine to perform multivariate pattern classification based on the brain activation during directed forgetting. The pattern of brain activity in directed forgetting of negative words allowed correct group classification with an overall accuracy of 75% (P=0.012). The brain regions which are critical for this discrimination showed abnormal activation when depressed participants were attempting to forget negative words. These results indicated that the abnormal neural circuitry when depressed individuals tried to forget the negative words might provide neurobiological markers for depression. PMID:26639452

  4. Abnormal spontaneous brain activity in minimal hepatic encephalopathy: resting-state fMRI study

    PubMed Central

    Zhong, Wei-Jia; Zhou, Zhi-Ming; Zhao, Jian-Nong; Wu, Wei; Guo, Da-Jing

    2016-01-01

    PURPOSE We aimed to assess the abnormality of baseline spontaneous brain activity in minimal hepatic encephalopathy (MHE) by amplitude of low frequency fluctuation (ALFF) and fraction ALFF (fALFF). METHODS A total of 14 MHE patients and 14 healthy controls were included in our study. Both ALFF and fALFF of functional magnetic resonance imaging were calculated for statistical analysis. RESULTS Compared with healthy controls, patients with MHE had significantly decreased ALFF in the bilateral medial prefrontal cortex (MPFC), left superior frontal gyrus, right precentral gyrus, left opercular part of inferior frontal gyrus, left gyrus rectus, bilateral precuneus, and the posterior lobe of right cerebellum; and they had significantly decreased fALFF in the bilateral MPFC, right middle frontal gyrus, right superior temporal gyrus, and the posterior lobe of left cerebellum. CONCLUSION ALFF and fALFF changes in many brain regions demonstrate abnormality of the spontaneous neuronal activity in MHE. Especially the impairment of right precuneus and left MPFC may play a critical role in manifestation of MHE. Changes of ALFF and fALFF in the precuneus and the MPFC can be used as a potential marker for MHE. PMID:26742646

  5. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    PubMed Central

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  6. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder.

    PubMed

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R; Fan, Jin

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

  7. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder

    PubMed Central

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T.; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R.

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

  8. Sources of abnormal EEG activity in the presence of brain lesions.

    PubMed

    Fernández-Bouzas, A; Harmony, T; Bosch, J; Aubert, E; Fernández, T; Valdés, P; Silva, J; Marosi, E; Martínez-López, M; Casián, G

    1999-04-01

    In routine clinical EEG, a common origin is assumed for delta and theta rhythms produced by brain lesions. In previous papers, we have provided some experimental support, based on High Resolution qEEG and dipole fitting in the frequency domain, for the hypothesis that delta and theta spectral power have independent origins related to lesion and edema respectively. This paper describes the results obtained with Frequency Domain VARETA (FD-VARETA) in a group of 13 patients with cortical space-occupying lesions, in order to: 1) Test the accuracy of FD-VARETA for the localization of brain lesions, and 2) To provide further support for the independent origin of delta and theta components. FD VARETA is a distributed inverse solution, constrained by the Montreal Neurological Institute probabilistic atlas that estimates the spectra of EEG sources. In all patients, logarithmic transformed source spectra were compared with age-matched normative values, defining the Z source spectrum. Maximum Z values were found in 10 patients within the delta band (1.56 to 3.12 Hz); the spatial extent of these sources in the atlas corresponded with the location of the tumors in the CT. In 2 patients with small metastases and large volumes of edema and in a patient showing only edema, maximum Z values were found between 4.29 and 5.12 Hz. The spatial extent of the sources at these frequencies was within the volume of the edema in the CT. These results provided strong support to the hypothesis that both delta and theta abnormal EEG activities are the counterparts of two different pathophysiological processes. PMID:10358783

  9. Adolescent Binge Drinking Linked to Abnormal Spatial Working Memory Brain Activation: Differential Gender Effects

    PubMed Central

    Squeglia, Lindsay M.; Schweinsburg, Alecia Dager; Pulido, Carmen; Tapert, Susan F.

    2011-01-01

    Background Binge drinking is prevalent during adolescence, and its effect on neurocognitive development is of concern. In adult and adolescent populations, heavy substance use has been associated with decrements in cognitive functioning, particularly on tasks of spatial working memory (SWM). Characterizing the gender-specific influences of heavy episodic drinking on SWM may help elucidate the early functional consequences of drinking on adolescent brain functioning. Methods 40 binge drinkers (13 females, 27 males) and 55 controls (24 females, 31 males) ages 16 to 19, completed neuropsychological testing, substance use interviews, and a spatial working memory task (SWM) during functional magnetic resonance imaging (fMRI). Results Significant binge drinking status x gender interactions were found (p<.05) in 8 brain regions spanning bilateral frontal, anterior cingulate, temporal, and cerebellar cortices. In all regions, female binge drinkers showed less SWM activation than female controls, while male bingers exhibited greater SWM response than male controls. For female binge drinkers, less activation was associated with poorer sustained attention and working memory performances (ps<.025). For male binge drinkers, greater activation was linked to better spatial performance (p<.025). Conclusion Binge drinking during adolescence is associated with gender-specific differences in frontal, temporal, and cerebellar brain activation during a SWM task, which in turn relate to cognitive performance. Activation correlates with neuropsychological performance, strengthening the argument that BOLD activation is both affected by alcohol use and is an important indicator of behavioral functioning. Females may be more vulnerable to the neurotoxic effects of heavy alcohol use during adolescence, while males may be more resilient to the deleterious effects of binge drinking. Future longitudinal research will examine the significance of SWM brain activation as an early neurocognitive

  10. Abnormal Baseline Brain Activity in Patients with Pulsatile Tinnitus: A Resting-State fMRI Study

    PubMed Central

    Han, Lv; Zhaohui, Liu; Fei, Yan; Ting, Li; Pengfei, Zhao; Wang, Du; Cheng, Dong; Pengde, Guo; Xiaoyi, Han; Xiao, Wang; Rui, Li; Zhenchang, Wang

    2014-01-01

    Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT) patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI) technique. The present study used unilateral PT patients (n = 42) and age-, sex-, and education-matched normal control subjects (n = 42) to investigate the changes in structural and amplitude of low-frequency (ALFF) of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG) and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients. PMID:24872895

  11. Dyslexic brain activation abnormalities in deep and shallow orthographies: A meta-analysis of 28 functional neuroimaging studies.

    PubMed

    Martin, Anna; Kronbichler, Martin; Richlan, Fabio

    2016-07-01

    We used coordinate-based meta-analysis to objectively quantify commonalities and differences of dyslexic functional brain abnormalities between alphabetic languages differing in orthographic depth. Specifically, we compared foci of under- and overactivation in dyslexic readers relative to nonimpaired readers reported in 14 studies in deep orthographies (DO: English) and in 14 studies in shallow orthographies (SO: Dutch, German, Italian, Swedish). The separate meta-analyses of the two sets of studies showed universal reading-related dyslexic underactivation in the left occipitotemporal cortex (including the visual word form area (VWFA)). The direct statistical comparison revealed higher convergence of underactivation for DO compared with SO in bilateral inferior parietal regions, but this abnormality disappeared when foci resulting from stronger dyslexic task-negative activation (i.e., deactivation relative to baseline) were excluded. Higher convergence of underactivation for DO compared with SO was further identified in the left inferior frontal gyrus (IFG) pars triangularis, left precuneus, and right superior temporal gyrus, together with higher convergence of overactivation in the left anterior insula. Higher convergence of underactivation for SO compared with DO was found in the left fusiform gyrus, left temporoparietal cortex, left IFG pars orbitalis, and left frontal operculum, together with higher convergence of overactivation in the left precentral gyrus. Taken together, the findings support the notion of a biological unity of dyslexia, with additional orthography-specific abnormalities and presumably different compensatory mechanisms. The results are discussed in relation to current functional neuroanatomical models of developmental dyslexia. Hum Brain Mapp 37:2676-2699, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27061464

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

    PubMed Central

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

    2015-01-01

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

  13. Abnormal intrinsic brain activity patterns in leukoaraiosis with and without cognitive impairment.

    PubMed

    Li, Chuanming; Yang, Jun; Yin, Xuntao; Liu, Chen; Zhang, Lin; Zhang, Xiaochun; Gui, Li; Wang, Jian

    2015-10-01

    The amplitude of low frequency fluctuations (ALFF) from resting-state functional MRI (rs-fMRI) signals can be used to detect intrinsic spontaneous brain activity and provide valuable insights into the pathomechanism of neural disease. In this study, we recruited 56 patients who had been diagnosed as having mild to severe leukoaraiosis. According to the neuropsychological tests, they were subdivided into a leukoaraiosis with cognitive impairment group (n = 28) and a leukoaraiosis without cognitive impairment group (n = 28). 28 volunteers were included as normal controls. We found that the three groups showed significant differences in ALFF in the brain regions of the right inferior occipital gyrus (IOG_R), left middle temporal gyrus (MTG_L), left precuneus (Pcu_L), right superior frontal gyrus (SFG_R) and right superior occipital gyrus (SOG_R). Compared with normal controls, the leukoaraiosis without cognitive impairment group exhibited significantly increased ALFF in the IOG_R, Pcu_L, SFG_R and SOG_R. While compared with leukoaraiosis without cognitive impairment group, the leukoaraiosis with cognitive impairment group showed significantly decreased ALFF in IOG_R, MTG_L, Pcu_L and SOG_R. A close negative correlation was found between the ALFF values of the MTG_L and the Montreal Cognitive Assessment (MoCA) scores. Our data demonstrate that white matter integrity and cognitive impairment are associated with different amplitude fluctuations of rs-fMRI signals. Leukoaraiosis is related to ALFF increases in IOG_R, Pcu_L, SFG_Orb_R and SOG_R. Decreased ALFF in MTG_L is characteristic of cognitive impairment and may aid in its early detection. PMID:26116811

  14. Abnormal Brain Activity in Social Reward Learning in Children with Autism Spectrum Disorder: An fMRI Study

    PubMed Central

    Choi, Uk-Su; Kim, Sun-Young; Sim, Hyeon Jeong; Lee, Seo-Young; Park, Sung-Yeon; Jeong, Joon-Sup; Seol, Kyeong In; Yoon, Hyo-Woon; Jhung, Kyungun; Park, Jee-In

    2015-01-01

    Purpose We aimed to determine whether Autism Spectrum Disorder (ASD) would show neural abnormality of the social reward system using functional MRI (fMRI). Materials and Methods 27 ASDs and 12 typically developing controls (TDCs) participated in this study. The social reward task was developed, and all participants performed the task during fMRI scanning. Results ASDs and TDCs with a social reward learning effect were selected on the basis of behavior data. We found significant differences in brain activation between the ASDs and TDCs showing a social reward learning effect. Compared with the TDCs, the ASDs showed reduced activity in the right dorsolateral prefrontal cortex, right orbitofrontal cortex, right parietal lobe, and occipital lobe; however, they showed increased activity in the right parahippocampal gyrus and superior temporal gyrus. Conclusion These findings suggest that there might be neural abnormality of the social reward learning system of ASDs. Although this study has several potential limitations, it presents novel findings in the different neural mechanisms of social reward learning in children with ASD and a possible useful biomarker of high-functioning ASDs. PMID:25837176

  15. Schizophrenia and abnormal brain network hubs

    PubMed Central

    Rubinov, Mikail; Bullmore, Ed.

    2013-01-01

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

  16. Developmental disruptions underlying brain abnormalities in ciliopathies

    PubMed Central

    Guo, Jiami; Higginbotham, Holden; Li, Jingjun; Nichols, Jackie; Hirt, Josua; Ghukasyan, Vladimir; Anton, E.S.

    2015-01-01

    Primary cilia are essential conveyors of signals underlying major cell functions. Cerebral cortical progenitors and neurons have a primary cilium. The significance of cilia function for brain development and function is evident in the plethora of developmental brain disorders associated with human ciliopathies. Nevertheless, the role of primary cilia function in corticogenesis remains largely unknown. Here we delineate the functions of primary cilia in the construction of cerebral cortex and their relevance to ciliopathies, using an shRNA library targeting ciliopathy genes known to cause brain disorders, but whose roles in brain development are unclear. We used the library to query how ciliopathy genes affect distinct stages of mouse cortical development, in particular neural progenitor development, neuronal migration, neuronal differentiation and early neuronal connectivity. Our results define the developmental functions of ciliopathy genes and delineate disrupted developmental events that are integrally related to the emergence of brain abnormalities in ciliopathies. PMID:26206566

  17. Abnormal activity of the MAPK- and cAMP-associated signaling pathways in frontal cortical areas in postmortem brain in schizophrenia.

    PubMed

    Funk, Adam J; McCullumsmith, Robert E; Haroutunian, Vahram; Meador-Woodruff, James H

    2012-03-01

    Recent evidence suggests that schizophrenia may result from alterations of integration of signaling mediated by multiple neurotransmitter systems. Abnormalities of associated intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. Proteins and phospho-proteins comprising mitogen activated protein kinase (MAPK) and 3'-5'-cyclic adenosine monophosphate (cAMP)-associated signaling pathways may be abnormally expressed in the anterior cingulate (ACC) and dorsolateral prefrontal cortex (DLPFC) in schizophrenia. Using western blot analysis we examined proteins of the MAPK- and cAMP-associated pathways in these two brain regions. Postmortem samples were used from a well-characterized collection of elderly patients with schizophrenia (ACC=36, DLPFC=35) and a comparison (ACC=33, DLPFC=31) group. Near-infrared intensity of IR-dye labeled secondary antisera bound to targeted proteins of the MAPK- and cAMP-associated signaling pathways was measured using LiCor Odyssey imaging system. We found decreased expression of Rap2, JNK1, JNK2, PSD-95, and decreased phosphorylation of JNK1/2 at T183/Y185 and PSD-95 at S295 in the ACC in schizophrenia. In the DLPFC, we found increased expression of Rack1, Fyn, Cdk5, and increased phosphorylation of PSD-95 at S295 and NR2B at Y1336. MAPK- and cAMP-associated molecules constitute ubiquitous intracellular signaling pathways that integrate extracellular stimuli, modify receptor expression and function, and regulate cell survival and neuroplasticity. These data suggest abnormal activity of the MAPK- and cAMP-associated pathways in frontal cortical areas in schizophrenia. These alterations may underlie the hypothesized hypoglutamatergic function in this illness. Together with previous findings, these data suggest that abnormalities of intracellular signaling pathways may contribute to the pathophysiology of schizophrenia. PMID:22048463

  18. Connectivity and functional profiling of abnormal brain structures in pedophilia

    PubMed Central

    Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-01-01

    Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  19. Connectivity and functional profiling of abnormal brain structures in pedophilia.

    PubMed

    Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-06-01

    Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  20. Impaired Associative Taste Learning and Abnormal Brain Activation in Kinase-Defective eEF2K Mice

    ERIC Educational Resources Information Center

    Gildish, Iness; Manor, David; David, Orit; Sharma, Vijendra; Williams, David; Agarwala, Usha; Wang, Xuemin; Kenney, Justin W.; Proud, Chris G.; Rosenblum, Kobi

    2012-01-01

    Memory consolidation is defined temporally based on pharmacological interventions such as inhibitors of mRNA translation (molecular consolidation) or post-acquisition deactivation of specific brain regions (systems level consolidation). However, the relationship between molecular and systems consolidation are poorly understood. Molecular…

  1. Abnormal spontaneous regional brain activity in primary insomnia: a resting-state functional magnetic resonance imaging study

    PubMed Central

    Li, Chao; Ma, Xiaofen; Dong, Mengshi; Yin, Yi; Hua, Kelei; Li, Meng; Li, Changhong; Zhan, Wenfeng; Li, Cheng; Jiang, Guihua

    2016-01-01

    Objective Investigating functional specialization is crucial for a complete understanding of the neural mechanisms of primary insomnia (PI). Resting-state functional magnetic resonance imaging (fMRI) is a useful tool to explore the functional specialization of PI. However, only a few studies have focused on the functional specialization of PI using resting-state fMRI and results of these studies were far from consistent. Thus, the current study aimed to investigate functional specialization of PI using resting-state fMRI with amplitude of low frequency fluctuations (ALFFs) algorithm. Methods In this study, 55 PI patients and 44 healthy controls were included. ALFF values were compared between the two groups using two-sample t-test. The relationship of abnormal ALFF values with clinical characteristics and duration of insomnia was investigated using Pearson’s correlation analysis. Results PI patients showed lower ALFF values in the left orbitofrontal cortex/inferior frontal gyrus, right middle frontal gyrus, left inferior parietal lobule, and bilateral cerebellum posterior lobes, while higher ALFF values in the right middle/inferior temporal that extended to the right occipital lobe. In addition, we found that the duration of PI negatively correlated with ALFF values in the left orbitofrontal cortex/inferior frontal gyrus, and the Pittsburgh Sleep Quality Index score negatively correlated with ALFF values in the left inferior parietal lobule. Conclusion The present study added information to limited studies on functional specialization and provided evidence for hyperarousal hypothesis in PI. PMID:27366068

  2. Abnormal Brain Activation in Neurofibromatosis Type 1: A Link between Visual Processing and the Default Mode Network

    PubMed Central

    Violante, Inês R.; Ribeiro, Maria J.; Cunha, Gil; Bernardino, Inês; Duarte, João V.; Ramos, Fabiana; Saraiva, Jorge; Silva, Eduardo; Castelo-Branco, Miguel

    2012-01-01

    Neurofibromatosis type 1 (NF1) is one of the most common single gene disorders affecting the human nervous system with a high incidence of cognitive deficits, particularly visuospatial. Nevertheless, neurophysiological alterations in low-level visual processing that could be relevant to explain the cognitive phenotype are poorly understood. Here we used functional magnetic resonance imaging (fMRI) to study early cortical visual pathways in children and adults with NF1. We employed two distinct stimulus types differing in contrast and spatial and temporal frequencies to evoke relatively different activation of the magnocellular (M) and parvocellular (P) pathways. Hemodynamic responses were investigated in retinotopically-defined regions V1, V2 and V3 and then over the acquired cortical volume. Relative to matched control subjects, patients with NF1 showed deficient activation of the low-level visual cortex to both stimulus types. Importantly, this finding was observed for children and adults with NF1, indicating that low-level visual processing deficits do not ameliorate with age. Moreover, only during M-biased stimulation patients with NF1 failed to deactivate or even activated anterior and posterior midline regions of the default mode network. The observation that the magnocellular visual pathway is impaired in NF1 in early visual processing and is specifically associated with a deficient deactivation of the default mode network may provide a neural explanation for high-order cognitive deficits present in NF1, particularly visuospatial and attentional. A link between magnocellular and default mode network processing may generalize to neuropsychiatric disorders where such deficits have been separately identified. PMID:22723888

  3. Clinical Correlation between Perverted Nystagmus and Brain MRI Abnormal Findings

    PubMed Central

    Han, Won-Gue; Yoon, Hee-Chul; Kim, Tae-Min; Rah, Yoon Chan

    2016-01-01

    Background and Objectives To analyze the clinical correlation between perverted nystagmus and brain magnetic resonance imaging (MRI) abnormal findings and to evaluate whether perverted nystagmus is clinically significant results of brain abnormal lesions or not. Subjects and Methods We performed medical charts review from January 2008 to July 2014, retrospectively. Patients who were suspected central originated vertigo at Frenzel goggles test were included among patients who visited our hospital. To investigate the correlation with nystagmus suspected central originated vertigo and brain MRI abnormal findings, we confirmed whether performing brain MRI or not. Then we exclude that patients not performed brain MRI. Results The number of patients with perverted nystagmus was 15, upbeating was 1 and down-beating was 14. Among these patients, 5 patients have brain MRI abnormal findings. However, 2 patients with MRI abnormal findings were not associated correctly with perverted nystagmus and only 3 patients with perverted nystagmus were considered central originated vertigo and further evaluation and treatment was performed by the department of neurology. Conclusions Perverted nystagmus was considered to the abnormalities at brain lesions, especially cerebellum, but neurologic symptoms and further evaluation were needed for exact diagnosis of central originated vertigo. PMID:27626081

  4. Abnormal brain scan with subacute extradural haematomas

    PubMed Central

    Morley, J. Barrie; Langford, Keith H.

    1970-01-01

    Four patients are described with proven subacute extradural haematomas, each with an abnormal cerebral scan of diagnostic assistance. A possible mechanism of production of the subacute extradural haematoma is discussed, and appears to be similar to the mechanism involved in the subacute subdural haematoma. The means by which the abnormal scan results in such cases is also examined, from which it appears that non-specific meningeal membrane inflammatory reaction surrounding the haematoma is significant. Images PMID:5478950

  5. Brief Report: Brain Mechanisms in Autism: Functional and Structural Abnormalities.

    ERIC Educational Resources Information Center

    Minshew, Nancy J.

    1996-01-01

    This paper summarizes results of research on functional and structural abnormalities of the brain in autism. The current concept of causation is seen to involve multiple biologic levels. A consistent profile of brain function and dysfunction across methods has been found and specific neuropathologic findings have been found; but some research…

  6. Structural brain abnormalities in cervical dystonia

    PubMed Central

    2013-01-01

    Background Idiopathic cervical dystonia is characterized by involuntary spasms, tremors or jerks. It is not restricted to a disturbance in the basal ganglia system because non-conventional voxel-based MRI morphometry (VBM) and diffusion tensor imaging (DTI) have detected numerous regional changes in the brains of patients. In this study scans of 24 patients with cervical dystonia and 24 age-and sex-matched controls were analysed using VBM, DTI and magnetization transfer imaging (MTI) using a voxel-based approach and a region-of-interest analysis. Results were correlated with UDRS, TWSTRS and disease duration. Results We found structural alterations in the basal ganglia; thalamus; motor cortex; premotor cortex; frontal, temporal and parietal cortices; visual system; cerebellum and brainstem of the patients with dystonia. Conclusions Cervical dystonia is a multisystem disease involving several networks such as the motor, sensory and visual systems. PMID:24131497

  7. Genetic abnormality predicts benefit for a rare brain tumor

    Cancer.gov

    A clinical trial has shown that addition of chemotherapy to radiation therapy leads to a near doubling of median survival time in patients with a form of brain tumor (oligodendroglioma) that carries a chromosomal abnormality called the 1p19q co-deletion.

  8. Morphometric Brain Abnormalities in Boys with Conduct Disorder

    ERIC Educational Resources Information Center

    Huebner, Thomas; Vloet, Timo D.; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R.; Herpertz, Sabine C.; Herpertz-Dahlmann, Beate

    2008-01-01

    Conduct disorder (CD) is associated with antisocial personality behavior that violates the basic rights of others. Results, on examining the structural brain aberrations in boys' CD, show that boys with CD and cormobid attention-deficit/hyperactivity disorder showed abnormalities in frontolimbic areas that could contribute to antisocial…

  9. Abnormal brain activation of adolescent internet addict in a ball-throwing animation task: possible neural correlates of disembodiment revealed by fMRI.

    PubMed

    Kim, Yeoung-Rang; Son, Jung-Woo; Lee, Sang-Ick; Shin, Chul-Jin; Kim, Sie-Kyeong; Ju, Gawon; Choi, Won-Hee; Oh, Jong-Hyun; Lee, Seungbok; Jo, Seongwoo; Ha, Tae Hyon

    2012-10-01

    While adolescent internet addicts are immersed in cyberspace, they are easily able to experience 'disembodied state'. The purposes of this study were to investigate the difference of brain activity between adolescent internet addicts and normal adolescents in a state of disembodiment, and to find the correlation between the activities of disembodiment-related areas and the behavioral characteristics related to internet addiction. The fMRI images were taken while the addiction group (N=17) and the control group (N=17) were asked to perform the task composed with ball-throwing animations. The task reflected on either self-agency about ball-throwing or location of a ball. And each block was shown with either different (Changing View) or same animations (Fixed View). The disembodiment-related condition was the interaction between Agency Task and Changing View. Within-group analyses revealed that the addiction group exhibited higher activation in the thalamus, bilateral precentral area, bilateral middle frontal area, and the area around the right temporo-parietal junction. And between-group analyses showed that the addiction group exhibited higher activation in the area near the left temporo-parieto-occipital junction, right parahippocampal area, and other areas than the control group. Finally, the duration of internet use was significantly correlated with the activity of posterior area of left middle temporal gyrus in the addiction group. These results show that the disembodiment-related activation of the brain is easily manifested in adolescent internet addicts. Internet addiction of adolescents could be significantly unfavorable for their brain development related with identity formation. PMID:22687465

  10. Brain abnormality segmentation based on l1-norm minimization

    NASA Astrophysics Data System (ADS)

    Zeng, Ke; Erus, Guray; Tanwar, Manoj; Davatzikos, Christos

    2014-03-01

    We present a method that uses sparse representations to model the inter-individual variability of healthy anatomy from a limited number of normal medical images. Abnormalities in MR images are then defined as deviations from the normal variation. More precisely, we model an abnormal (pathological) signal y as the superposition of a normal part ~y that can be sparsely represented under an example-based dictionary, and an abnormal part r. Motivated by a dense error correction scheme recently proposed for sparse signal recovery, we use l1- norm minimization to separate ~y and r. We extend the existing framework, which was mainly used on robust face recognition in a discriminative setting, to address challenges of brain image analysis, particularly the high dimensionality and low sample size problem. The dictionary is constructed from local image patches extracted from training images aligned using smooth transformations, together with minor perturbations of those patches. A multi-scale sliding-window scheme is applied to capture anatomical variations ranging from fine and localized to coarser and more global. The statistical significance of the abnormality term r is obtained by comparison to its empirical distribution through cross-validation, and is used to assign an abnormality score to each voxel. In our validation experiments the method is applied for segmenting abnormalities on 2-D slices of FLAIR images, and we obtain segmentation results consistent with the expert-defined masks.

  11. Volumetric brain abnormalities in polysubstance use disorder patients

    PubMed Central

    Noyan, Cemal Onur; Kose, Samet; Nurmedov, Serdar; Metin, Baris; Darcin, Aslı Enez; Dilbaz, Nesrin

    2016-01-01

    Aim Polysubstance users represent the largest group of patients seeking treatment at addiction and rehabilitation clinics in Turkey. There is little knowledge about the structural brain abnormalities seen in polysubstance users. This study was conducted to examine the structural brain differences between polysubstance use disorder patients and healthy control subjects using voxel-based morphometry. Methods Forty-six male polysubstance use disorder patients in the early abstinence period and 30 healthy male controls underwent structural magnetic resonance imaging scans. Voxel-based morphometry analysis was performed to examine gray matter (GM) abnormality differences. Results Polysubstance use disorder patients displayed significantly smaller GM volume in the thalamus, temporal pole, superior frontal gyrus, cerebellum, gyrus rectus, occipital lobe, anterior cingulate cortex, superior temporal gyrus, and postcentral gyrus. Conclusion A widespread and smaller GM volume has been found at different regions of the frontal, temporal, occipital, and parietal lobes, cerebellum, and anterior cingulate cortex in polysubstance users. PMID:27358566

  12. Volume estimation of brain abnormalities in MRI data

    NASA Astrophysics Data System (ADS)

    Suprijadi, Pratama, S. H.; Haryanto, F.

    2014-02-01

    The abnormality of brain tissue always becomes a crucial issue in medical field. This medical condition can be recognized through segmentation of certain region from medical images obtained from MRI dataset. Image processing is one of computational methods which very helpful to analyze the MRI data. In this study, combination of segmentation and rendering image were used to isolate tumor and stroke. Two methods of thresholding were employed to segment the abnormality occurrence, followed by filtering to reduce non-abnormality area. Each MRI image is labeled and then used for volume estimations of tumor and stroke-attacked area. The algorithms are shown to be successful in isolating tumor and stroke in MRI images, based on thresholding parameter and stated detection accuracy.

  13. Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development

    PubMed Central

    Girardi, G; Fraser, J; Lennen, R; Vontell, R; Jansen, M; Hutchison, G

    2015-01-01

    In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders. PMID:25245499

  14. MRI-based methods to detect placental and fetal brain abnormalities in utero.

    PubMed

    Girardi, Guillermina

    2016-04-01

    There are very few methods for screening women for pregnancy complications. Identification of pregnancies at risk would be of enormous clinical significance as would influence decisions made about pregnancy management and delivery. Adverse pregnancy outcomes such as obstetric antiphospholipid syndrome (APS) and preterm birth (PTB), characterized by placental insufficiency and abnormal fetal brain development, in mice and humans have been associated with activation of inflammatory pathways, in particular the complement cascade. Recently, antibodies against C3 activation products conjugated with contrast agent ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were used to detect non-invasively sites of inflammation within the placenta and the fetal brain in mouse models of APS and PTB. In utero, magnetic resonance imaging (MRI)-based detection of C3 deposition in the placenta in the APS model was associated with signs of placental insufficiency and intrauterine growth restriction. In both models, fetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration. Proton magnetic resonance spectroscopy ((1)H MRS), another non invasive method, is used to identify metabolic abnormalities to predict fetal brain abnormalities. This review describes the recent development of preclinical MRI-based methods for the detection of inflammatory markers of placental insufficiency and abnormal fetal brain development and metabolism to predict pregnancy outcomes. PMID:26187242

  15. Early Blood Gas Abnormalities and the Preterm Brain

    PubMed Central

    Leviton, Alan; Allred, Elizabeth; Kuban, Karl C. K.; Dammann, Olaf; O'Shea, T. Michael; Hirtz, Deborah; Schreiber, Michael D.; Paneth, Nigel

    2010-01-01

    The authors explored associations between blood gas abnormalities in more than 1,000 preterm infants during the first postnatal days and indicators of neonatal brain damage. During 2002–2004, women delivering infants before 28 weeks’ gestation at one of 14 participating institutions in 5 US states were asked to enroll in the study. The authors compared infants with blood gas values in the highest or lowest quintile for gestational age and postnatal day (extreme value) on at least 1 of the first 3 postnatal days with the remainder of the subjects, with separate analyses for blood gas abnormalities on multiple days and for partial pressure of oxygen in the alveolar gas of <35. Outcomes analyzed were ventriculomegaly and an echolucent lesion on an ultrasound scan in the neonatal intensive care unit, and cerebral palsy, microcephaly, and a low score on a Bayley Scale of Infant Development at 24 months. Every blood gas derangement (hypoxemia, hyperoxemia, hypocapnia, hypercapnia, and acidosis) was associated with multiple indicators of brain damage. However, for some, the associations were seen with only 1 day of exposure; others were evident with 2 or more days’ exposure. Findings suggest that individual blood gas derangements do not increase brain damage risk. Rather, the multiple derangements associated with indicators of brain damage might be indicators of immaturity/vulnerability and illness severity. PMID:20807736

  16. Abuse of Amphetamines and Structural Abnormalities in Brain

    PubMed Central

    Berman, Steven; O’Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D.

    2009-01-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse, and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques that include manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common, and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre-existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  17. Abuse of amphetamines and structural abnormalities in the brain.

    PubMed

    Berman, Steven; O'Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D

    2008-10-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques including manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  18. Electrocardiographic abnormalities and cardiac arrhythmias in structural brain lesions.

    PubMed

    Katsanos, Aristeidis H; Korantzopoulos, Panagiotis; Tsivgoulis, Georgios; Kyritsis, Athanassios P; Kosmidou, Maria; Giannopoulos, Sotirios

    2013-07-31

    Cardiac arrhythmias and electrocardiographic abnormalities are frequently observed after acute cerebrovascular events. The precise mechanism that leads to the development of these arrhythmias is still uncertain, though increasing evidence suggests that it is mainly due to autonomic nervous system dysregulation. In massive brain lesions sympathetic predominance and parasympathetic withdrawal during the first 72 h are associated with the occurrence of severe secondary complications in the first week. Right insular cortex lesions are also related with sympathetic overactivation and with a higher incidence of electrocardiographic abnormalities, mostly QT prolongation, in patients with ischemic stroke. Additionally, female sex and hypokalemia are independent risk factors for severe prolongation of the QT interval which subsequently results in malignant arrhythmias and poor outcome. The prognostic value of repolarization changes commonly seen after aneurysmal subarachnoid hemorrhage, such as ST segment, T wave, and U wave abnormalities, still remains controversial. In patients with traumatic brain injury both intracranial hypertension and cerebral hypoperfusion correlate with low heart rate variability and increased mortality. Given that there are no firm guidelines for the prevention or treatment of the arrhythmias that appear after cerebral incidents this review aims to highlight important issues on this topic. Selected patients with the aforementioned risk factors could benefit from electrocardiographic monitoring, reassessment of the medications that prolong QTc interval, and administration of antiadrenergic agents. Further research is required in order to validate these assumptions and to establish specific therapeutic strategies. PMID:22809542

  19. Gyrification brain abnormalities as predictors of outcome in anorexia nervosa.

    PubMed

    Favaro, Angela; Tenconi, Elena; Degortes, Daniela; Manara, Renzo; Santonastaso, Paolo

    2015-12-01

    Gyrification brain abnormalities are considered a marker of early deviations from normal developmental trajectories and a putative predictor of poor outcome in psychiatric disorders. The aim of this study was to explore cortical folding morphology in patients with anorexia nervosa (AN). A MRI brain study was conducted on 38 patients with AN, 20 fully recovered patients, and 38 healthy women. Local gyrification was measured with procedures implemented in FreeSurfer. Vertex-wise comparisons were carried out to compare: (1) AN patients and healthy women; (2) patients with a full remission at a 3-year longitudinal follow-up assessment and patients who did not recover. AN patients exhibited significantly lower gyrification when compared with healthy controls. Patients with a poor 3-year outcome had significantly lower baseline gyrification when compared to both healthy women and patients with full recovery at follow-up, even after controlling for the effects of duration of illness and gray matter volume. No significant correlation has been found between gyrification, body mass index, amount of weight loss, onset age, and duration of illness. Brain gyrification significantly predicted outcome at follow-up even after controlling for the effects of duration of illness and other clinical prognostic factors. Although the role of starvation in determining our findings cannot be excluded, our study showed that brain gyrification might be a predictor of outcome in AN. Further studies are needed to understand if brain gyrification abnormalities are indices of early neurodevelopmental alterations, the consequence of starvation, or the interaction between both factors. PMID:26374960

  20. Abnormal Activity Detection Using Pyroelectric Infrared Sensors

    PubMed Central

    Luo, Xiaomu; Tan, Huoyuan; Guan, Qiuju; Liu, Tong; Zhuo, Hankz Hankui; Shen, Baihua

    2016-01-01

    Healthy aging is one of the most important social issues. In this paper, we propose a method for abnormal activity detection without any manual labeling of the training samples. By leveraging the Field of View (FOV) modulation, the spatio-temporal characteristic of human activity is encoded into low-dimension data stream generated by the ceiling-mounted Pyroelectric Infrared (PIR) sensors. The similarity between normal training samples are measured based on Kullback-Leibler (KL) divergence of each pair of them. The natural clustering of normal activities is discovered through a self-tuning spectral clustering algorithm with unsupervised model selection on the eigenvectors of a modified similarity matrix. Hidden Markov Models (HMMs) are employed to model each cluster of normal activities and form feature vectors. One-Class Support Vector Machines (OSVMs) are used to profile the normal activities and detect abnormal activities. To validate the efficacy of our method, we conducted experiments in real indoor environments. The encouraging results show that our method is able to detect abnormal activities given only the normal training samples, which aims to avoid the laborious and inconsistent data labeling process. PMID:27271632

  1. Abnormal Activity Detection Using Pyroelectric Infrared Sensors.

    PubMed

    Luo, Xiaomu; Tan, Huoyuan; Guan, Qiuju; Liu, Tong; Zhuo, Hankz Hankui; Shen, Baihua

    2016-01-01

    Healthy aging is one of the most important social issues. In this paper, we propose a method for abnormal activity detection without any manual labeling of the training samples. By leveraging the Field of View (FOV) modulation, the spatio-temporal characteristic of human activity is encoded into low-dimension data stream generated by the ceiling-mounted Pyroelectric Infrared (PIR) sensors. The similarity between normal training samples are measured based on Kullback-Leibler (KL) divergence of each pair of them. The natural clustering of normal activities is discovered through a self-tuning spectral clustering algorithm with unsupervised model selection on the eigenvectors of a modified similarity matrix. Hidden Markov Models (HMMs) are employed to model each cluster of normal activities and form feature vectors. One-Class Support Vector Machines (OSVMs) are used to profile the normal activities and detect abnormal activities. To validate the efficacy of our method, we conducted experiments in real indoor environments. The encouraging results show that our method is able to detect abnormal activities given only the normal training samples, which aims to avoid the laborious and inconsistent data labeling process. PMID:27271632

  2. Chromosome abnormalities in chronic active hepatitis

    PubMed Central

    Stefanescu, D. T.; Moanga, M.; Teodorescu, M.; Brucher, J.

    1972-01-01

    An investigation on human peripheral blood lymphocyte chromosomes in chronic active hepatitis was carried out. A higher percentage of chromatid and chromosome lesions was recorded in all patients studied as compared with control groups—normal individuals, healthy subjects who had suffered from acute viral hepatitis, patients with alcoholic liver disease, and patients with mechanical jaundice due to cancer. The possible origin of these abnormalities is discussed. PMID:5076805

  3. Neuroendocrine abnormalities in patients with traumatic brain injury

    NASA Technical Reports Server (NTRS)

    Yuan, X. Q.; Wade, C. E.

    1991-01-01

    This article provides an overview of hypothalamic and pituitary alterations in brain trauma, including the incidence of hypothalamic-pituitary damage, injury mechanisms, features of the hypothalamic-pituitary defects, and major hypothalamic-pituitary disturbances in brain trauma. While hypothalamic-pituitary lesions have been commonly described at postmortem examination, only a limited number of clinical cases of traumatic hypothalamic-pituitary dysfunction have been reported, probably because head injury of sufficient severity to cause hypothalamic and pituitary damage usually leads to early death. With the improvement in rescue measures, an increasing number of severely head-injured patients with hypothalamic-pituitary dysfunction will survive to be seen by clinicians. Patterns of endocrine abnormalities following brain trauma vary depending on whether the injury site is in the hypothalamus, the anterior or posterior pituitary, or the upper or lower portion of the pituitary stalk. Injury predominantly to the hypothalamus can produce dissociated ACTH-cortisol levels with no response to insulin-induced hypoglycemia and a limited or failed metopirone test, hypothyroxinemia with a preserved thyroid-stimulating hormone response to thyrotropin-releasing hormone, low gonadotropin levels with a normal response to gonadotropin-releasing hormone, a variable growth hormone (GH) level with a paradoxical rise in GH after glucose loading, hyperprolactinemia, the syndrome of inappropriate ADH secretion (SIADH), temporary or permanent diabetes insipidus (DI), disturbed glucose metabolism, and loss of body temperature control. Severe damage to the lower pituitary stalk or anterior lobe can cause low basal levels of all anterior pituitary hormones and eliminate responses to their releasing factors. Only a few cases showed typical features of hypothalamic or pituitary dysfunction. Most severe injuries are sufficient to damage both structures and produce a mixed endocrine picture

  4. Anatomical and functional brain abnormalities in unmedicated major depressive disorder

    PubMed Central

    Yang, Xiao; Ma, Xiaojuan; Li, Mingli; Liu, Ye; Zhang, Jian; Huang, Bin; Zhao, Liansheng; Deng, Wei; Li, Tao; Ma, Xiaohong

    2015-01-01

    Background Using magnetic resonance imaging (MRI) and resting-state functional magnetic resonance imaging (rsfMRI) to explore the mechanism of brain structure and function in unmedicated patients with major depressive disorder (MDD). Patients and methods Fifty patients with MDD and 50 matched healthy control participants free of psychotropic medication underwent high-resolution structural and rsfMRI scanning. Optimized diffeomorphic anatomical registration through exponentiated lie algebra and the Data Processing Assistant for rsfMRI were used to find potential differences in gray-matter volume (GMV) and regional homogeneity (ReHo) between the two groups. A Pearson correlation model was used to analyze associations of morphometric and functional changes with clinical symptoms. Results Compared to healthy controls, patients with MDD showed significant GMV increase in the left posterior cingulate gyrus and GMV decrease in the left lingual gyrus (P<0.001, uncorrected). In ReHo analysis, values were significantly increased in the left precuneus and decreased in the left putamen (P<0.001, uncorrected) in patients with MDD compared to healthy controls. There was no overlap between anatomical and functional changes. Linear correlation suggested no significant correlation between mean GMV values within regions with anatomical abnormality and ReHo values in regions with functional abnormality in the patient group. These changes were not significantly correlated with symptom severity. Conclusion Our study suggests a dissociation pattern of brain regions with anatomical and functional alterations in unmedicated patients with MDD, especially with regard to GMV and ReHo. PMID:26425096

  5. Persistent endothelial abnormalities and blood-brain barrier leak in primary and secondary progressive multiple sclerosis.

    PubMed

    Leech, S; Kirk, J; Plumb, J; McQuaid, S

    2007-02-01

    Epithelial and endothelial tight junctions are pathologically altered in infectious, inflammatory, neoplastic and other diseases. Previously, we described such abnormalities, associated with serum protein leak, in tight junctions of the blood-brain barrier endothelium, in lesional and normal-appearing white matter (NAWM) in secondary progressive (SP) and acute multiple sclerosis (MS). This work is extended here to lesions and NAWM in primary progressive multiple sclerosis (PPMS) and to cortical grey matter in PPMS and SPMS. Immunocytochemistry and semiquantitative confocal microscopy for the tight junction protein zonula occludens 1 (ZO-1) was performed on snap-frozen sections from PPMS (n = 6) and controls (n = 5). Data on 2103 blood vessels were acquired from active lesions (n = 10), inactive lesions (n = 15), NAWM (n = 42) and controls (n = 20). Data on 1218 vessels were acquired from normal-appearing grey matter (PPMS, 5; SPMS, 6; controls, 5). In PPMS abnormal ZO-1 expression in active white matter lesions and NAWM, was found in 42% and 13% of blood vessels, respectively, comparable to previous data from acute and SPMS. In chronic white matter plaques, however, abnormalities were considerably more frequent (37%) in PPMS than in SPMS. Abnormality was also more frequent in normal-appearing grey matter in SPMS (23%) than in PPMS (10%). In summary, abnormal tight junctions in both SPMS and PPMS are most frequent in active white matter lesions but persist in inactive lesions, particularly in PPMS. Abnormal tight junctions are also common in normal-appearing grey matter in SPMS. Persistent endothelial abnormality with leak (PEAL) is therefore widespread but variably expressed in MS and may contribute to disease progression. PMID:17239011

  6. The influence of brain abnormalities on psychosocial development, criminal history and paraphilias in sexual murderers.

    PubMed

    Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

    2005-09-01

    The aim of this study was to investigate the number and type of brain abnormalities and their influence on psychosocial development, criminal history and paraphilias in sexual murderers. We analyzed psychiatric court reports of 166 sexual murderers and compared a group with notable signs of brain abnormalities (N = 50) with those without any signs (N = 116). Sexual murderers with brain abnormalities suffered more from early behavior problems. They were less likely to cohabitate with the victim at the time of the homicide and had more victims at the age of six years or younger. Psychiatric diagnoses revealed a higher total number of paraphilias: Transvestic fetishism and paraphilias not otherwise specified were more frequent in offenders with brain abnormalities. A binary logistic regression identified five predictors that accounted for 46.8% of the variance explaining the presence of brain abnormalities. Our results suggest the importance of a comprehensive neurological and psychological examination of this special offender group. PMID:16225232

  7. Mapping abnormal subcortical brain morphometry in an elderly HIV + cohort

    PubMed Central

    Wade, Benjamin S.C.; Valcour, Victor G.; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Gutman, Boris A.; Thompson, Paul M.

    2015-01-01

    Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%. PMID:26640768

  8. Memory activation reveals abnormal EEG in preclinical Huntington's disease.

    PubMed

    van der Hiele, Karin; Jurgens, Caroline K; Vein, Alla A; Reijntjes, Robert H A M; Witjes-Ané, Marie-Noëlle W; Roos, Raymund A C; van Dijk, Gert; Middelkoop, Huub A M

    2007-04-15

    The EEG is potentially useful as a marker of early Huntington's disease (HD). In dementia, the EEG during a memory activation challenge showed abnormalities where the resting EEG did not. We investigated whether memory activation also reveals EEG abnormalities in preclinical HD. Sixteen mutation carriers for HD and 13 nonmutation carriers underwent neurological, neuropsychological, MRI and EEG investigations. The EEG was registered during a rest condition, i.e. eyes closed, and a working memory task. In each condition we determined absolute power in the theta (4-8 Hz) and alpha (8-13 Hz) bands and subsequently calculated relative alpha power. The EEG during eyes closed did not differ between groups. The EEG during memory activation showed less relative alpha power in mutation carriers as compared to nonmutation carriers, even though memory performance was similar [F (1,27) = 10.87; P = 0.003]. Absolute powers also showed less alpha power [F (1,27) = 7.02; P = 0.013] but similar theta power. No correlations were found between absolute and relative alpha power on the one hand and neuropsychological scores, motor scores or number of CAG repeats on the other. In conclusion, memory activation reveals functional brain changes in Huntington's disease before clinical signs become overt. PMID:17266047

  9. Co-localisation of abnormal brain structure and function in specific language impairment

    PubMed Central

    Badcock, Nicholas A.; Bishop, Dorothy V.M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677

  10. Abnormal subcellular localization of GABAA receptor subunits in schizophrenia brain.

    PubMed

    Mueller, T M; Remedies, C E; Haroutunian, V; Meador-Woodruff, J H

    2015-01-01

    Inhibitory neurotransmission is primarily mediated by γ-aminobutyric acid (GABA) activating synaptic GABA type A receptors (GABA(A)R). In schizophrenia, presynaptic GABAergic signaling deficits are among the most replicated findings; however, postsynaptic GABAergic deficits are less well characterized. Our lab has previously demonstrated that although there is no difference in total protein expression of the α1-6, β1-3 or γ2 GABA(A)R subunits in the superior temporal gyrus (STG) in schizophrenia, the α1, β1 and β2 GABA(A)R subunits are abnormally N-glycosylated. N-glycosylation is a posttranslational modification that has important functional roles in protein folding, multimer assembly and forward trafficking. To investigate the impact that altered N-glycosylation has on the assembly and trafficking of GABA(A)Rs in schizophrenia, this study used western blot analysis to measure the expression of α1, α2, β1, β2 and γ2 GABA(A)R subunits in subcellular fractions enriched for endoplasmic reticulum (ER) and synapses (SYN) from STG of schizophrenia (N = 16) and comparison (N = 14) subjects and found evidence of abnormal localization of the β1 and β2 GABA(A)R subunits and subunit isoforms in schizophrenia. The β2 subunit is expressed as three isoforms at 52 kDa (β2(52 kDa)), 50 kDa (β2(50 kDa)) and 48 kDa (β2(48 kDa)). In the ER, we found increased total β2 GABA(A)R subunit (β2(ALL)) expression driven by increased β2(50 kDa), a decreased ratio of β(248 kDa):β2(ALL) and an increased ratio of β2(50 kDa):β2(48 kDa). Decreased ratios of β1:β2(ALL) and β1:β2(50 kDa) in both the ER and SYN fractions and an increased ratio of β2(52 kDa):β(248 kDa) at the synapse were also identified in schizophrenia. Taken together, these findings provide evidence that alterations of N-glycosylation may contribute to GABAergic signaling deficits in schizophrenia by disrupting the assembly and trafficking of GABA(A)Rs. PMID:26241350

  11. Abnormal subcellular localization of GABAA receptor subunits in schizophrenia brain

    PubMed Central

    Mueller, T M; Remedies, C E; Haroutunian, V; Meador-Woodruff, J H

    2015-01-01

    Inhibitory neurotransmission is primarily mediated by γ-aminobutyric acid (GABA) activating synaptic GABA type A receptors (GABAAR). In schizophrenia, presynaptic GABAergic signaling deficits are among the most replicated findings; however, postsynaptic GABAergic deficits are less well characterized. Our lab has previously demonstrated that although there is no difference in total protein expression of the α1–6, β1–3 or γ2 GABAAR subunits in the superior temporal gyrus (STG) in schizophrenia, the α1, β1 and β2 GABAAR subunits are abnormally N-glycosylated. N-glycosylation is a posttranslational modification that has important functional roles in protein folding, multimer assembly and forward trafficking. To investigate the impact that altered N-glycosylation has on the assembly and trafficking of GABAARs in schizophrenia, this study used western blot analysis to measure the expression of α1, α2, β1, β2 and γ2 GABAAR subunits in subcellular fractions enriched for endoplasmic reticulum (ER) and synapses (SYN) from STG of schizophrenia (N=16) and comparison (N=14) subjects and found evidence of abnormal localization of the β1 and β2 GABAAR subunits and subunit isoforms in schizophrenia. The β2 subunit is expressed as three isoforms at 52 kDa (β252 kDa), 50 kDa (β250 kDa) and 48 kDa (β248 kDa). In the ER, we found increased total β2 GABAAR subunit (β2ALL) expression driven by increased β250 kDa, a decreased ratio of β248 kDa:β2ALL and an increased ratio of β250 kDa:β248 kDa. Decreased ratios of β1:β2ALL and β1:β250 kDa in both the ER and SYN fractions and an increased ratio of β252 kDa:β248 kDa at the synapse were also identified in schizophrenia. Taken together, these findings provide evidence that alterations of N-glycosylation may contribute to GABAergic signaling deficits in schizophrenia by disrupting the assembly and trafficking of GABAARs. PMID:26241350

  12. Brain white matter abnormality in a newborn infant with congenital adrenal hyperplasia.

    PubMed

    Kaga, Akimune; Saito-Hakoda, Akiko; Uematsu, Mitsugu; Kamimura, Miki; Kanno, Junko; Kure, Shigeo; Fujiwara, Ikuma

    2013-10-01

    Several studies have described brain white matter abnormalities on magnetic resonance imaging (MRI) in children and adults with congenital adrenal hyperplasia (CAH), while the brain MRI findings of newborn infants with CAH have not been clarified. We report a newborn boy with CAH who presented brain white matter abnormality on MRI. He was diagnosed as having salt-wasting CAH with a high 17-OHP level at neonatal screening and was initially treated with hydrocortisone at 8 days of age. On day 11 after birth, he had a generalized tonic seizure. No evidence of serum electrolyte abnormalities was observed. Brain MRI revealed white matter abnormalities that consisted of bilateral small diffuse hyperintensities on T1-weighted images with slightly low intensity on T2-weighted images in the watershed area. Several factors associated with brain white matter abnormalities in adults with CAH, such as increasing age, hypertension, diabetes and corticosteroid replacement, were not applicable. Although the cause of the phenomenon in this case is unclear, brain white matter abnormality could be observed in newborn infants with CAH as well as in adult patients. PMID:24170965

  13. Neurological Gait Abnormalities Moderate the Functional Brain Signature of the Posture First Hypothesis.

    PubMed

    Holtzer, Roee; Verghese, Joe; Allali, Gilles; Izzetoglu, Meltem; Wang, Cuiling; Mahoney, Jeannette R

    2016-03-01

    The posture first hypothesis suggests that under dual-task walking conditions older adults prioritize gait over cognitive task performance. Functional neural confirmation of this hypothesis, however, is lacking. Herein, we determined the functional neural correlates of the posture first hypothesis and hypothesized that the presence of neurological gait abnormalities (NGA) would moderate associations between brain activations, gait and cognitive performance. Using functional near-infrared spectroscopy we assessed changes in oxygenated hemoglobin levels in the pre-frontal cortex (PFC) during normal walk and walk while talk (WWT) conditions in a large cohort of non-demented older adults (n = 236; age = 75.5 ± 6.49 years; female = 51.7 %). NGA were defined as central (due to brain diseases) or peripheral (neuropathic gait) following a standardized neurological examination protocol. Double dissociations between brain activations and behavior emerged as a function of NGA. Higher oxygenation levels during WWT were related to better cognitive performance (estimate = 0.145; p < 0.001) but slower gait velocity (estimate = -6.336, p < 0.05) among normals. In contrast, higher oxygenation levels during WWT among individuals with peripheral NGA were associated with worse cognitive performance (estimate = -0.355; p < 0.001) but faster gait velocity (estimate = 14.855; p < 0.05). Increased activation in the PFC during locomotion may have a compensatory function that is designed to support gait among individuals with peripheral NGA. PMID:26613725

  14. Investigating individual differences in brain abnormalities in autism.

    PubMed Central

    Salmond, C H; de Haan, M; Friston, K J; Gadian, D G; Vargha-Khadem, F

    2003-01-01

    Autism is a psychiatric syndrome characterized by impairments in three domains: social interaction, communication, and restricted and repetitive behaviours and interests. Recent findings implicate the amygdala in the neurobiology of autism. In this paper, we report the results of a series of novel experimental investigations focusing on the structure and function of the amygdala in a group of children with autism. The first section attempts to determine if abnormality of the amygdala can be identified in an individual using magnetic resonance imaging in vivo. Using single-case voxel-based morphometric analyses, abnormality in the amygdala was detected in half the children with autism. Abnormalities in other regions were also found. In the second section, emotional modulation of the startle response was investigated in the group of autistic children. Surprisingly, there were no significant differences between the patterns of emotional modulation of the startle response in the autistic group compared with the controls. PMID:12639337

  15. Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

    2010-01-01

    Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

  16. Infantile Autism and Computerized Tomography Brain-Scan Findings: Specific versus Nonspecific Abnormalities.

    ERIC Educational Resources Information Center

    Balottin, Umberto; And Others

    1989-01-01

    The study of computerized tomography brain-scan findings with 45 autistic and 19 control subjects concluded that autism is nonspecifically associated with brain-scan abnormalities, and that other nonorganic, as well as organic, factors should be taken into account. (Author/DB)

  17. The Neural Underpinnings of Associative Learning in Health and Psychosis: How Can Performance Be Preserved When Brain Responses Are Abnormal?

    PubMed Central

    Murray, Graham K.; Corlett, Philip R.; Fletcher, Paul C.

    2010-01-01

    Associative learning experiments in schizophrenia and other psychoses reveal subtle abnormalities in patients’ brain responses. These are sometimes accompanied by intact task performance. An important question arises: How can learning occur if the brain system is not functioning normally? Here, we examine a series of possible explanations for this apparent discrepancy: (1) standard brain activation patterns may be present in psychosis but partially obscured by greater noise, (2) brain signals may be more sensitive to real group differences than behavioral measures, and (3) patients may achieve comparable levels of performance to control subjects by employing alternative or compensatory neural strategies. We consider these explanations in relation to data from causal- and reward-learning imaging experiments in first-episode psychosis patients. The findings suggest that a combination of these factors may resolve the question of why performance is sometimes preserved when brain patterns are disrupted. PMID:20154201

  18. Developmental vitamin D deficiency causes abnormal brain development.

    PubMed

    Eyles, D W; Feron, F; Cui, X; Kesby, J P; Harms, L H; Ko, P; McGrath, J J; Burne, T H J

    2009-12-01

    There is now clear evidence that vitamin D is involved in brain development. Our group is interested in environmental factors that shape brain development and how this may be relevant to neuropsychiatric diseases including schizophrenia. The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia namely: (1) the excess winter/spring birth rate, (2) increased incidence of the disease in 2nd generation Afro-Caribbean migrants and (3) increased urban birth rate. Moreover we have published two pieces of direct epidemiological support for this hypothesis in patients. In order to establish the "Biological Plausibility" of this hypothesis we have developed an animal model to study the effect of DVD deficiency on brain development. We do this by removing vitamin D from the diet of female rats prior to breeding. At birth we return all dams to a vitamin D containing diet. Using this procedure we impose a transient, gestational vitamin D deficiency, while maintaining normal calcium levels throughout. The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing. In this review we summarise the literature addressing the function of vitamin D on neuronal and non-neuronal cells as well as in vivo results from DVD-deficient animals. Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that

  19. Abnormal deposits of chromium in the pathological human brain.

    PubMed Central

    Duckett, S

    1986-01-01

    Three patients presented with encephalopathies: an undiagnosed degenerative disease of the brain, a degenerative cerebral disease in a patient with a myeloma but without a myelomatous deposit in the CNS and a malignant astrocytoma. Perivascular pallidal deposits (vascular siderosis) containing chromium, phosphorus and calcium plus sometimes traces of other elements were present in the three cases. Such deposits were present in the pallidal parenchyma and around vessels in the cerebellum in one case. Calcium and phosphorus are always present in any CNS calcification but the presence of chromium has not been reported. Chromium and its compounds (ingested, injected or inhaled) are toxic to humans and animals in trace doses. Approximately 900 cases of chromium intoxication have been reported and usually have had dermatological or pulmonary lesions (including cancer) but there is no report of involvement of the CNS. Sublethal doses of chromium nitrate injected intraperitoneally in rats and rabbits results in the presence of chromium in the brain. A thorough investigation was made to find the source of the chromium in these patients. Chromium was found to be present in trace amounts in the radiological contrast agents administered to these patients and in the KCl replacement solution and in mylanta, an antacid, given to one case. The evidence that chromium induced pathological changes in these three brains is circumstantial but shows that chromium can penetrate the human brain. This study indicates that vascular siderosis found in the brains of the majority of middle-aged and elderly humans is not simply an anecdotal pathological curiosity, but that it can serve as a route of entry for toxic products into the brain. Images PMID:3958742

  20. Predicting intrinsic brain activity.

    PubMed

    Craddock, R Cameron; Milham, Michael P; LaConte, Stephen M

    2013-11-15

    Multivariate supervised learning methods exhibit a remarkable ability to decode externally driven sensory, behavioral, and cognitive states from functional neuroimaging data. Although they are typically applied to task-based analyses, supervised learning methods are equally applicable to intrinsic effective and functional connectivity analyses. The obtained models of connectivity incorporate the multivariate interactions between all brain regions simultaneously, which will result in a more accurate representation of the connectome than the ones available with standard bivariate methods. Additionally the models can be applied to decode or predict the time series of intrinsic brain activity of a region from an independent dataset. The obtained prediction accuracy provides a measure of the integration between a brain region and other regions in its network, as well as a method for evaluating acquisition and preprocessing pipelines for resting state fMRI data. This article describes a method for learning multivariate models of connectivity. The method is applied in the non-parametric prediction accuracy, influence, and reproducibility-resampling (NPAIRS) framework, to study the regional variation of prediction accuracy and reproducibility (Strother et al., 2002). The resulting spatial distribution of these metrics is consistent with the functional hierarchy proposed by Mesulam (1998). Additionally we illustrate the utility of the multivariate regression connectivity modeling method for optimizing experimental parameters and assessing the quality of functional neuroimaging data. PMID:23707580

  1. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

  2. Brain Structure Abnormalities in Adolescent Girls with Conduct Disorder

    ERIC Educational Resources Information Center

    Fairchild, Graeme; Hagan, Cindy C.; Walsh, Nicholas D.; Passamonti, Luca; Calder, Andrew J.; Goodyer, Ian M.

    2013-01-01

    Background: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD.…

  3. Thrombotic thrombocytopenic purpura: MR demonstration of reversible brain abnormalities

    SciTech Connect

    D'Aprile, P.; Carella, A.; Pagliarulo, R. ); Farchi, G. )

    1994-01-01

    We report a case of thrombotic thrombocytopenic purpura evaluated by MR, Multiple hyperintense foci on the TS-weighted images, observed principally in the brain stem and in the region of the basal nuclei, and neurologic signs disappeared after 15 days of therapy. 6 refs., 2 figs.

  4. scMRI Reveals Large-Scale Brain Network Abnormalities in Autism

    PubMed Central

    Zielinski, Brandon A.; Anderson, Jeffrey S.; Froehlich, Alyson L.; Prigge, Molly B. D.; Nielsen, Jared A.; Cooperrider, Jason R.; Cariello, Annahir N.; Fletcher, P. Thomas; Alexander, Andrew L.; Lange, Nicholas; Bigler, Erin D.; Lainhart, Janet E.

    2012-01-01

    Autism is a complex neurological condition characterized by childhood onset of dysfunction in multiple cognitive domains including socio-emotional function, speech and language, and processing of internally versus externally directed stimuli. Although gross brain anatomic differences in autism are well established, recent studies investigating regional differences in brain structure and function have yielded divergent and seemingly contradictory results. How regional abnormalities relate to the autistic phenotype remains unclear. We hypothesized that autism exhibits distinct perturbations in network-level brain architecture, and that cognitive dysfunction may be reflected by abnormal network structure. Network-level anatomic abnormalities in autism have not been previously described. We used structural covariance MRI to investigate network-level differences in gray matter structure within two large-scale networks strongly implicated in autism, the salience network and the default mode network, in autistic subjects and age-, gender-, and IQ-matched controls. We report specific perturbations in brain network architecture in the salience and default-mode networks consistent with clinical manifestations of autism. Extent and distribution of the salience network, involved in social-emotional regulation of environmental stimuli, is restricted in autism. In contrast, posterior elements of the default mode network have increased spatial distribution, suggesting a ‘posteriorization’ of this network. These findings are consistent with a network-based model of autism, and suggest a unifying interpretation of previous work. Moreover, we provide evidence of specific abnormalities in brain network architecture underlying autism that are quantifiable using standard clinical MRI. PMID:23185305

  5. Abnormal brain structure in youth who commit homicide

    PubMed Central

    Cope, L.M.; Ermer, E.; Gaudet, L.M.; Steele, V.R.; Eckhardt, A.L.; Arbabshirani, M.R.; Caldwell, M.F.; Calhoun, V.D.; Kiehl, K.A.

    2014-01-01

    Background Violence that leads to homicide results in an extreme financial and emotional burden on society. Juveniles who commit homicide are often tried in adult court and typically spend the majority of their lives in prison. Despite the enormous costs associated with homicidal behavior, there have been no serious neuroscientific studies examining youth who commit homicide. Methods Here we use neuroimaging and voxel-based morphometry to examine brain gray matter in incarcerated male adolescents who committed homicide (n = 20) compared with incarcerated offenders who did not commit homicide (n = 135). Two additional control groups were used to understand further the nature of gray matter differences: incarcerated offenders who did not commit homicide matched on important demographic and psychometric variables (n = 20) and healthy participants from the community (n = 21). Results Compared with incarcerated adolescents who did not commit homicide (n = 135), incarcerated homicide offenders had reduced gray matter volumes in the medial and lateral temporal lobes, including the hippocampus and posterior insula. Feature selection and support vector machine learning classified offenders into the homicide and non-homicide groups with 81% overall accuracy. Conclusions Our results indicate that brain structural differences may help identify those at the highest risk for committing serious violent offenses. PMID:24936430

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

    PubMed

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

    2016-04-01

    Individuals with focal epilepsy have heterogeneous sites of seizure origin. However, there may be brain regions that are common to most cases of intractable focal epilepsy. In this study, we aim to identify these using multivariate analysis of task-free functional MRI. Fourteen subjects with extratemporal focal epilepsy and 14 healthy controls were included in the study. Task-free functional MRI data were used to calculate voxel-wise regional connectivity with regional homogeneity (ReHo) and weighted degree centrality (DCw), in addition to regional activity using fraction of amplitude of low-frequency fluctuations (fALFF). Multivariate pattern analysis was applied to each of these metrics to discriminate brain areas that differed between focal epilepsy subjects and healthy controls. ReHo and DCw classified focal epilepsy subjects from healthy controls with high accuracy (89.3% and 75%, respectively). However, fALFF did not significantly classify patients from controls. Increased regional network activity in epilepsy subjects was seen in the ipsilateral piriform cortex, insula, and thalamus, in addition to the dorsal anterior cingulate cortex and lateral frontal cortices. Decreased regional connectivity was observed in the ventromedial prefrontal cortex, as well as lateral temporal cortices. Patients with extratemporal focal epilepsy have common areas of abnormality (ReHo and DCw measures), including the ipsilateral piriform cortex, temporal neocortex, and ventromedial prefrontal cortex. ReHo shows additional increase in the "salience network" that includes anterior insula and anterior cingulate cortex. DCw showed additional effects in the ipsilateral thalamus and striatum. These brain areas may represent key regional network properties underlying focal epilepsy. PMID:26537783

  7. Absence of Glial α-Dystrobrevin Causes Abnormalities of the Blood-Brain Barrier and Progressive Brain Edema*

    PubMed Central

    Lien, Chun Fu; Mohanta, Sarajo Kumar; Frontczak-Baniewicz, Malgorzata; Swinny, Jerome D.; Zablocka, Barbara; Górecki, Dariusz C.

    2012-01-01

    The blood-brain barrier (BBB) plays a key role in maintaining brain functionality. Although mammalian BBB is formed by endothelial cells, its function requires interactions between endotheliocytes and glia. To understand the molecular mechanisms involved in these interactions is currently a major challenge. We show here that α-dystrobrevin (α-DB), a protein contributing to dystrophin-associated protein scaffolds in astrocytic endfeet, is essential for the formation and functioning of BBB. The absence of α-DB in null brains resulted in abnormal brain capillary permeability, progressively escalating brain edema, and damage of the neurovascular unit. Analyses in situ and in two-dimensional and three-dimensional in vitro models of BBB containing α-DB-null astrocytes demonstrated these abnormalities to be associated with loss of aquaporin-4 water and Kir4.1 potassium channels from glial endfeet, formation of intracellular vacuoles in α-DB-null astrocytes, and defects of the astrocyte-endothelial interactions. These caused deregulation of tight junction proteins in the endothelia. Importantly, α-DB but not dystrophins showed continuous expression throughout development in BBB models. Thus, α-DB emerges as a central organizer of dystrophin-associated protein in glial endfeet and a rare example of a glial protein with a role in maintaining BBB function. Its abnormalities might therefore lead to BBB dysfunction. PMID:23043099

  8. Preliminary research on abnormal brain detection by wavelet-energy and quantum- behaved PSO.

    PubMed

    Zhang, Yudong; Ji, Genlin; Yang, Jiquan; Wang, Shuihua; Dong, Zhengchao; Phillips, Preetha; Sun, Ping

    2016-04-29

    It is important to detect abnormal brains accurately and early. The wavelet-energy (WE) was a successful feature descriptor that achieved excellent performance in various applications; hence, we proposed a WE based new approach for automated abnormal detection, and reported its preliminary results in this study. The kernel support vector machine (KSVM) was used as the classifier, and quantum-behaved particle swarm optimization (QPSO) was introduced to optimize the weights of the SVM. The results based on a 5 × 5-fold cross validation showed the performance of the proposed WE + QPSO-KSVM was superior to ``DWT + PCA + BP-NN'', ``DWT + PCA + RBF-NN'', ``DWT + PCA + PSO-KSVM'', ``WE + BPNN'', ``WE +$ KSVM'', and ``DWT $+$ PCA $+$ GA-KSVM'' w.r.t. sensitivity, specificity, and accuracy. The work provides a novel means to detect abnormal brains with excellent performance. PMID:27163327

  9. Abnormal Corticospinal Excitability in Traumatic Diffuse Axonal Brain Injury

    PubMed Central

    Bernabeu, Montse; Demirtas-Tatlidede, Asli; Opisso, Eloy; Lopez, Raquel; Tormos, Jose Mª

    2009-01-01

    Abstract This study aimed to investigate the cortical motor excitability characteristics in diffuse axonal injury (DAI) due to severe traumatic brain injury (TBI). A variety of excitatory and inhibitory transcranial magnetic stimulation (TMS) paradigms were applied to primary motor cortices of 17 patients and 11 healthy controls. The parameters of testing included resting motor threshold (MT), motor evoked potential (MEP) area under the curve, input-output curves, MEP variability, and silent period (SP) duration. The patient group overall revealed a higher MT, smaller MEP areas, and narrower recruitment curves compared to normal controls (p < 0.05). The alterations in excitability were more pronounced with an increase in DAI severity (p < 0.005) and the presence of motor impairment (p < 0.05), while co-existence of focal lesions did not affect the degree of MEP changes. MEP variability was significantly lower in the group with motor impairment only (p < 0.05). The intracortical inhibition, as revealed by SP duration, did not exhibit any significant differences in any of the patient groups. In conclusion, our findings expand the concept that impairment of the excitatory and inhibitory phenomena in the motor cortex does not proceed in parallel and demonstrate distinct patterns of aberrations in TBI. Furthermore, these data suggest that alterations in the corticospinal excitatory mechanisms are determined predominantly by the severity of DAI, and show a significant relationship with clinical motor dysfunction following severe trauma diffusely affecting the motor cortical connections. In severe TBI, motor and functional recovery might be linked to restitution of normal corticospinal mechanisms, indexed by normalization of the cortical excitability parameters. PMID:19604100

  10. Abnormal Parietal Brain Function in ADHD: Replication and Extension of Previous EEG Beta Asymmetry Findings

    PubMed Central

    Hale, T. Sigi; Kane, Andrea M.; Tung, Kelly L.; Kaminsky, Olivia; McGough, James J.; Hanada, Grant; Loo, Sandra K.

    2014-01-01

    Background: Abundant work indicates ADHD abnormal posterior brain structure and function, including abnormal structural and functional asymmetries and reduced corpus callosum size. However, this literature has attracted considerably less research interest than fronto-striatal findings. Objective: To help address this imbalance, the current study replicates and extends our previous work showing abnormal parietal brain function in ADHD adults during the Conner’s Continuous Performance Test (CPT). Method: Our previous study found that ADHD adults had increased rightward EEG beta (16–21 Hz) asymmetry in inferior parietal brain regions during the CPT (p = 0.00001), and that this metric exhibited a lack of normal correlation (i.e., observed in controls) with beta asymmetry at temporal–parietal regions. We re-tested these effects in a new ADHD sample and with both new and old samples combined. We additionally examined: (a) EEG asymmetry in multiple frequency bands, (b) unilateral effects for all asymmetry findings, and (c) the association between EEG asymmetry and a battery of cognitive tests. Results: We replicated our original findings by demonstrating abnormal rightward inferior parietal beta asymmetry in adults with ADHD during the CPT, and again this metric exhibited abnormal reduced correlation to temporal–parietal beta asymmetry. Novel analyses also demonstrated a broader pattern of rightward beta and theta asymmetry across inferior, superior, and temporal–parietal brain regions, and showed that rightward parietal asymmetry in ADHD was atypically associated with multiple cognitive tests. Conclusion: Abnormal increased rightward parietal EEG beta asymmetry is an important feature of ADHD. We speculate that this phenotype may occur with any form of impaired capacity for top-down task-directed control over sensory encoding functions, and that it may reflect associated increase of attentional shifting and compensatory sustained/selective attention. PMID

  11. Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer*

    PubMed Central

    Kiebish, Michael A.; Han, Xianlin; Cheng, Hua; Chuang, Jeffrey H.; Seyfried, Thomas N.

    2008-01-01

    Otto Warburg first proposed that cancer originated from irreversible injury to mitochondrial respiration, but the structural basis for this injury has remained elusive. Cardiolipin (CL) is a complex phospholipid found almost exclusively in the inner mitochondrial membrane and is intimately involved in maintaining mitochondrial functionality and membrane integrity. Abnormalities in CL can impair mitochondrial function and bioenergetics. We used shotgun lipidomics to analyze CL content and composition in highly purified brain mitochondria from the C57BL/6J (B6) and VM/Dk (VM) inbred strains and from subcutaneously grown brain tumors derived from these strains to include an astrocytoma and ependymoblastoma (B6 tumors), a stem cell tumor, and two microgliomas (VM tumors). Major abnormalities in CL content or composition were found in all tumors. The compositional abnormalities involved an abundance of immature molecular species and deficiencies of mature molecular species, suggesting major defects in CL synthesis and remodeling. The tumor CL abnormalities were also associated with significant reductions in both individual and linked electron transport chain activities. A mathematical model was developed to facilitate data interpretation. The implications of our findings to the Warburg cancer theory are discussed. PMID:18703489

  12. How Can We Identify Ictal and Interictal Abnormal Activity?

    PubMed Central

    Fisher, Robert S.; Scharfman, Helen E.; deCurtis, Marco

    2015-01-01

    The International League Against Epilepsy (ILAE) defined a seizure as “a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.” This definition has been used since the era of Hughlings Jackson, and does not take into account subsequent advances made in epilepsy and neuroscience research. The clinical diagnosis of a seizure is empirical, based upon constellations of certain signs and symptoms, while simultaneously ruling out a list of potential imitators of seizures. Seizures should be delimited in time, but the borders of ictal (during a seizure), interictal (between seizures) and postictal (after a seizure) often are indistinct. EEG recording is potentially very helpful for confirmation, classification and localization. About a half-dozen common EEG patterns are encountered during seizures. Clinicians rely on researchers to answer such questions as why seizures start, spread and stop, whether seizures involve increased synchrony, the extent to which extra-cortical structures are involved, and how to identify the seizure network and at what points interventions are likely to be helpful. Basic scientists have different challenges in use of the word ‘seizure,’ such as distinguishing seizures from normal behavior, which would seem easy but can be very difficult because some rodents have EEG activity during normal behavior that resembles spike-wave discharge or bursts of rhythmic spiking. It is also important to define when a seizure begins and stops so that seizures can be quantified accurately for pre-clinical studies. When asking what causes seizures, the transition to a seizure and differentiating the pre-ictal, ictal and post-ictal state is also important because what occurs before a seizure could be causal and may warrant further investigation for that reason. These and other issues are discussed by three epilepsy researchers with clinical and basic science expertise. PMID:25012363

  13. Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

    SciTech Connect

    Fujibayashi, Y.; Yamamoto, S.; Waki, A. |

    1996-05-01

    DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies. In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.

  14. Brain Activities and Educational Technology

    ERIC Educational Resources Information Center

    Riza, Emel

    2002-01-01

    There are close relationships between brain activities and educational technology. Brain is very important and so complicated part in our bodies. From long time scientists pay attention to that part and did many experiments, but they just reached little information like a drop in the sea. However from time to time they gave us some light to…

  15. Cranial index of children with normal and abnormal brain development in Sokoto, Nigeria: A comparative study

    PubMed Central

    Musa, Muhammad Awwal; Zagga, Abdullahi Daudu; Danfulani, Mohammed; Tadros, Aziz Abdo; Ahmed, Hamid

    2014-01-01

    Background: Abnormal brain development due to neurodevelopmental disorders in children has always been an important concern, but yet has to be considered as a significant public health problem, especially in the low- and middle-income countries including Nigeria. Aims: The aim of this study is to determine whether abnormal brain development in the form of neurodevelopmental disorders causes any deviation in the cranial index of affected children. Materials and Methods: This is a comparative study on the head length, head width, and cranial index of 112 children (72 males and 40 females) diagnosed with at least one abnormal problem in brain development, in the form of a neurodevelopmental disorder (NDD), in comparison with that of 218 normal growing children without any form of NDD (121 males and 97 females), aged 0-18 years old seen at the Usmanu Danfodiyo University Teaching Hospital, Sokoto, over a period of six months, June to December, 2012. The head length and head width of the children was measured using standard anatomical landmarks and cranial index calculated. The data obtained was entered into the Microsoft excel worksheet and analyzed using SPSS version 17. Results: The mean Cephalic Index for normal growing children with normal brain development was 79.82 ± 3.35 and that of the children with abnormal brain development was 77.78 ± 2.95 and the difference between the two groups was not statistically significant (P > 0.05). Conclusion: It can be deduced from this present study that the cranial index does not change in children with neurodevelopmental disorders. PMID:24966551

  16. A mechanical model predicts morphological abnormalities in the developing human brain

    NASA Astrophysics Data System (ADS)

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

  17. A mechanical model predicts morphological abnormalities in the developing human brain

    PubMed Central

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-01-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism. PMID:25008163

  18. Brain Gym. Simple Activities for Whole Brain Learning.

    ERIC Educational Resources Information Center

    Dennison, Paul E.; Dennison, Gail E.

    This booklet contains simple movements and activities that are used with students in Educational Kinesiology to enhance their experience of whole brain learning. Whole brain learning through movement repatterning and Brain Gym activities enable students to access those parts of the brain previously unavailable to them. These movements of body and…

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

    PubMed Central

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

    2013-01-01

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

  20. Abnormal trigeminal nerve microstructure and brain white matter in idiopathic trigeminal neuralgia.

    PubMed

    DeSouza, Danielle D; Hodaie, Mojgan; Davis, Karen D

    2014-01-01

    Idiopathic trigeminal neuralgia (TN) is classically associated with neurovascular compression (NVC) of the trigeminal nerve at the root entry zone (REZ), but NVC-induced structural alterations are not always apparent on conventional imaging. Previous studies report lower fractional anisotropy (FA) in the affected trigeminal nerves of TN patients using diffusion tensor imaging (DTI). However, it is not known if TN patients have trigeminal nerve abnormalities of mean, radial, or axial diffusivity (MD, RD, AD - metrics linked to neuroinflammation and edema) or brain white matter (WM) abnormalities. DTI scans in 18 right-sided TN patients and 18 healthy controls were retrospectively analyzed to extract FA, RD, AD, and MD from the trigeminal nerve REZ, and Tract-Based Spatial Statistics (TBSS) was used to assess brain WM. In patients, the affected trigeminal nerve had lower FA, and higher RD, AD, and MD was found bilaterally compared to controls. Group TBSS (P<0.05, corrected) showed patients had lower FA and increased RD, MD, and AD in brain WM connecting areas involved in the sensory and cognitive-affective dimensions of pain, attention, and motor functions, including the corpus callosum, cingulum, posterior corona radiata, and superior longitudinal fasciculus. These data indicate that TN patients have abnormal tissue microstructure in their affected trigeminal nerves, and as a possible consequence, WM microstructural alterations in the brain. These findings suggest that trigeminal nerve structural abnormalities occur in TN, even if not apparent on gross imaging. Furthermore, MD and RD findings suggest that neuroinflammation and edema may contribute to TN pathophysiology. PMID:23999058

  1. The "selfish brain" hypothesis for metabolic abnormalities in bipolar disorder and schizophrenia.

    PubMed

    Mansur, Rodrigo Barbachan; Brietzke, Elisa

    2012-09-01

    Metabolic abnormalities are frequent in patients with schizophrenia and bipolar disorder (BD), leading to a high prevalence of diabetes and metabolic syndrome in this population. Moreover, mortality rates among patients are higher than in the general population, especially due to cardiovascular diseases. Several neurobiological systems involved in energy metabolism have been shown to be altered in both illnesses; however, the cause of metabolic abnormalities and how they relate to schizophrenia and BD pathophysiology are still largely unknown. The "selfish brain" theory is a recent paradigm postulating that, in order to maintain its own energy supply stable, the brain modulates energy metabolism in the periphery by regulation of both allocation and intake of nutrients. We hypothesize that the metabolic alterations observed in these disorders are a result of an inefficient regulation of the brain energy supply and its compensatory mechanisms. The selfish brain theory can also expand our understanding of stress adaptation and neuroprogression in schizophrenia and BD, and, overall, can have important clinical implications for both illnesses. PMID:25923003

  2. Fueling and imaging brain activation

    PubMed Central

    Dienel, Gerald A

    2012-01-01

    Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron–astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models. PMID:22612861

  3. Fueling and imaging brain activation.

    PubMed

    Dienel, Gerald A

    2012-01-01

    Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron-astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models. PMID:22612861

  4. Thalamic abnormalities are a cardinal feature of alcohol-related brain dysfunction.

    PubMed

    Pitel, Anne Lise; Segobin, Shailendra H; Ritz, Ludivine; Eustache, Francis; Beaunieux, Hélène

    2015-07-01

    Two brain networks are particularly affected by the harmful effect of chronic and excessive alcohol consumption: the circuit of Papez and the frontocerebellar circuit, in both of which the thalamus plays a key role. Shrinkage of the thalamus is more severe in alcoholics with Korsakoff's syndrome (KS) than in those without neurological complication (AL). In accordance with the gradient effect of thalamic abnormalities between AL and KS, the pattern of brain dysfunction in the Papez's circuit results in anterograde amnesia in KS and only mild-to-moderate episodic memory disorders in AL. On the opposite, dysfunction of the frontocerebellar circuit results in a similar pattern of working memory and executive deficits in the AL and KS. Several hypotheses, mutually compatible, can be drawn to explain that the severe thalamic shrinkage observed in KS has different consequences in the neuropsychological profile associated with the two brain networks. PMID:25108034

  5. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    PubMed Central

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  6. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

    PubMed

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  7. A Cross-Sectional Study of Regional Brain Volume Abnormalities in Lesch-Nyhan Disease and its Variants

    PubMed Central

    Schretlen, David J.; Varvaris, Mark; Ho, Tiffany E.; Vannorsdall, Tracy D.; Gordon, Barry; Harris, James C.; Jinnah, H. A.

    2014-01-01

    Background Lesch-Nyhan disease (LND) is a rare, X-linked, neurodevelopmental metabolic disorder that results from a near-complete lack of hypoxanthine phosphoribosyl-transferase enzyme activity. LND is characterized by hyperuricemia, motor neurological abnormalities, recurrent self-injury, and cognitive impairment, but its neural substrates remain poorly understood. Methods In this cross-sectional study, we measured gray matter abnormalities in 21 persons with LND, 17 with an attenuated variant of the phenotype (LNV), and 33 healthy controls using voxel-based morphometry. We conducted an analysis of covariance to identify group differences in regional gray matter volume (GMV), followed by six pair-wise post-hoc group comparisons. Findings Patients with LND showed 20% smaller intracranial volumes (17% gray and 26% white matter) than healthy adults. The largest differences were found in basal ganglia, frontotemporal, and limbic regions, with sparing of parieto-occipital regions. The gray matter volumes of LNV participants invariably fell between those of patients with classical LND and healthy controls. Compared to healthy adults, patients with LND showed additional GMV reductions in the temporal lobe and left lateralized structures, and patients with LNV showed additional reductions in lingual and precuneus regions with sparing of right frontal and temporal regions. LND participants showed reductions in the ventral striatum and prefrontal areas relative to LNV. Interpretation This study of brain morphology reveals regional abnormalities associated with known neurological and behavioral deficits in persons with LND. It also revealed that patients with LNV show milder gray matter abnormalities in many of the same brain regions and preservation of GMV in other regions which could provide important clues to the neural substrates of differences between thephenotypes. PMID:24383089

  8. Abnormal Neural Activation to Faces in the Parents of Children with Autism.

    PubMed

    Yucel, G H; Belger, A; Bizzell, J; Parlier, M; Adolphs, R; Piven, J

    2015-12-01

    Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the "Broad Autism Phenotype " (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality ("BAP+"). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. PMID:25056573

  9. Age at First Episode Modulates Diagnosis-Related Structural Brain Abnormalities in Psychosis.

    PubMed

    Pina-Camacho, Laura; Del Rey-Mejías, Ángel; Janssen, Joost; Bioque, Miquel; González-Pinto, Ana; Arango, Celso; Lobo, Antonio; Sarró, Salvador; Desco, Manuel; Sanjuan, Julio; Lacalle-Aurioles, Maria; Cuesta, Manuel J; Saiz-Ruiz, Jerónimo; Bernardo, Miguel; Parellada, Mara

    2016-03-01

    Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12-35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15-20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18-20 y). The AFP group also had age-constant (12-35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis. PMID:26371339

  10. Fish consumption and risk of subclinical brain abnormalities on MRI in older adults

    PubMed Central

    Virtanen, J K.; Siscovick, D S.; Longstreth, W T.; Kuller, L H.; Mozaffarian, D

    2008-01-01

    Objective: To investigate the association between fish consumption and subclinical brain abnormalities. Methods: In the population-based Cardiovascular Health Study, 3,660 participants age ≥65 underwent an MRI scan in 1992–1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses. Results: After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish ≥3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54–1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities. Conclusions: Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits. GLOSSARY ARR = absolute risk reduction; BMI = body mass index; CHD = coronary heart disease; CHS = Cardiovascular Health Study; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; FFQ = food frequency questionnaire; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; PUFA = polyunsaturated fatty acid; RR = relative risk. PMID:18678827

  11. Posterior brain white matter abnormalities in older adults with probable mild cognitive impairment

    PubMed Central

    Cooley, Sarah A.; Cabeen, Ryan P.; Laidlaw, David H.; Conturo, Thomas E.; Lane, Elizabeth M.; Heaps, Jodi M.; Bolzenius, Jacob D.; Baker, Laurie M.; Salminen, Lauren E.; Scott, Staci E.; Paul, Robert H.

    2014-01-01

    Objective Much of the mild cognitive impairment (MCI) neuroimaging literature has exclusively focused on regions associated with Alzheimer’s disease. Little research has examined white matter abnormalities of other brain regions, including those associated with visual processing, despite evidence that other brain abnormalities appear in these regions in early disease stages. Method Diffusion tensor imaging (DTI) was utilized to examine participants (n = 44) that completed baseline imaging as part of a longitudinal healthy aging study. Participants were divided into two groups based on scores from the Montreal Cognitive Assessment (MoCA), a brief screening tool for MCI. Participants who scored < 26 were defined as “probable MCI” while those who scored ≥ 26 were labled cognitively healthy. Two DTI indices were analyzed including fractional anisotropy (FA) and mean diffusivity (MD). DTI values for white matter in the lingual gyrus, cuneus, pericalcarine, fusiform gyrus and all four lobes were compared using MANOVA. Regression analyses examined the relationship between DTI indices and total MoCA score. Results Results revealed significantly lower FA in the probable MCI group in the cuneus, fusiform, pericalcarine and occipital lobe, and significantly higher MD in the temporal lobe. Fusiform FA and temporal lobe MD were significantly related to total MoCA score after accounting for age and education. Conclusions Results indicate that there are posterior white matter microstructural changes in individuals with probable MCI. These differences demonstrate that white matter abnormalities are evident among individuals with probable MCI in regions beyond those commonly associated with Alzheimer’s disease and anterior brain aging patterns. PMID:25523313

  12. Brain abnormalities in human obesity: a voxel-based morphometric study.

    PubMed

    Pannacciulli, Nicola; Del Parigi, Angelo; Chen, Kewei; Le, Duc Son N T; Reiman, Eric M; Tataranni, Pietro A

    2006-07-15

    Obesity is accompanied by damage to several tissues. Overweight is a risk factor for Alzheimer's disease and other neurodegenerative disorders. Whether structural abnormalities associated with excess body fat may also occur in the brain is unknown. We sought to determine to what extent excess body fat is associated with regional alterations in brain structure using voxel-based morphometry (VBM), a whole-brain unbiased technique based upon high-definition 3D magnetic resonance imaging (MRI) scans normalized into a common standard space and allowing for an objective assessment of neuroanatomical differences throughout the brain. We studied 24 obese (11 male, 13 female; age: 32 +/- 8 years; body mass index [BMI]: 39.4 +/- 4.7 kg/m2) and 36 lean (25 male, 11 female; mean age: 33 +/- 9 years; BMI: 22.7 +/- 2.2 kg/m2) non-diabetic Caucasians. In comparison with the group of lean subjects, the group of obese individuals had significantly lower gray matter density in the post-central gyrus, frontal operculum, putamen, and middle frontal gyrus (P < 0.01 after adjustment for sex, age, handedness, global tissue density, and multiple comparisons). BMI was negatively associated with GM density of the left post-central gyrus in obese but not lean subjects. This study identified structural brain differences in human obesity in several brain areas previously involved in the regulation of taste, reward, and behavioral control. These alterations may either precede obesity, representing a neural marker of increased propensity to gaining weight, or occur as a consequence of obesity, indicating that also the brain is affected by increased adiposity. PMID:16545583

  13. Skeletal and Brain Abnormalities in Fucosidosis, a Rare Lysosomal Storage Disorder

    PubMed Central

    Malatt, Camille; Koning, Jeffrey L.; Naheedy, John

    2015-01-01

    Fucosidosis is a rare genetic lysosomal storage disorder caused by a deficiency in alpha- L-fucosidase. We present a case of a 4-year, 11-month-old girl with developmental delay, as well as skeletal and brain abnormalities as shown on X-ray and MRI. Her spinal X- rays demonstrated lumbar kyphosis and anterior beaking of lumbar vertebral bodies. Lower iliac segment constriction, increased angulation of the acetabular roof, and widening of the ribs were apparent on abdominal X-ray. Her brain MRI illustrated symmetric T1 hyperintensity and T2 hypointensity of the bilateral globi pallidi. The case report highlights clinical and imaging findings of this rare disease. PMID:26622931

  14. Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities.

    PubMed

    Driggers, Rita W; Ho, Cheng-Ying; Korhonen, Essi M; Kuivanen, Suvi; Jääskeläinen, Anne J; Smura, Teemu; Rosenberg, Avi; Hill, D Ashley; DeBiasi, Roberta L; Vezina, Gilbert; Timofeev, Julia; Rodriguez, Fausto J; Levanov, Lev; Razak, Jennifer; Iyengar, Preetha; Hennenfent, Andrew; Kennedy, Richard; Lanciotti, Robert; du Plessis, Adre; Vapalahti, Olli

    2016-06-01

    The current outbreak of Zika virus (ZIKV) infection has been associated with an apparent increased risk of congenital microcephaly. We describe a case of a pregnant woman and her fetus infected with ZIKV during the 11th gestational week. The fetal head circumference decreased from the 47th percentile to the 24th percentile between 16 and 20 weeks of gestation. ZIKV RNA was identified in maternal serum at 16 and 21 weeks of gestation. At 19 and 20 weeks of gestation, substantial brain abnormalities were detected on ultrasonography and magnetic resonance imaging (MRI) without the presence of microcephaly or intracranial calcifications. On postmortem analysis of the fetal brain, diffuse cerebral cortical thinning, high ZIKV RNA loads, and viral particles were detected, and ZIKV was subsequently isolated. PMID:27028667

  15. Cerebral abnormalities in cocaine abusers: Demonstration by SPECT perfusion brain scintigraphy. Work in progress

    SciTech Connect

    Tumeh, S.S.; Nagel, J.S.; English, R.J.; Moore, M.; Holman, B.L. )

    1990-09-01

    Single photon emission computed tomography (SPECT) perfusion brain scans with iodine-123 isopropyl iodoamphetamine (IMP) were obtained in 12 subjects who acknowledged using cocaine on a sporadic to a daily basis. The route of cocaine administration varied from nasal to intravenous. Concurrent abuse of other drugs was also reported. None of the patients were positive for human immunodeficiency virus. Brain scans demonstrated focal defects in 11 subjects, including seven who were asymptomatic, and no abnormality in one. Among the findings were scattered focal cortical deficits, which were seen in several patients and which ranged in severity from small and few to multiple and large, with a special predilection for the frontal and temporal lobes. No perfusion deficits were seen on I-123 SPECT images in five healthy volunteers. Focal alterations in cerebral perfusion are seen commonly in asymptomatic drug users, and these focal deficits are readily depicted by I-123 IMP SPECT.

  16. Motor Network Plasticity and Low-Frequency Oscillations Abnormalities in Patients with Brain Gliomas: A Functional MRI Study

    PubMed Central

    Niu, Chen; Zhang, Ming; Min, Zhigang; Rana, Netra; Zhang, Qiuli; Liu, Xin; Li, Min; Lin, Pan

    2014-01-01

    Brain plasticity is often associated with the process of slow-growing tumor formation, which remodels neural organization and optimizes brain network function. In this study, we aimed to investigate whether motor function plasticity would display deficits in patients with slow-growing brain tumors located in or near motor areas, but who were without motor neurological deficits. We used resting-state functional magnetic resonance imaging to probe motor networks in 15 patients with histopathologically confirmed brain gliomas and 15 age-matched healthy controls. All subjects performed a motor task to help identify individual motor activity in the bilateral primary motor cortex (PMC) and supplementary motor area (SMA). Frequency-based analysis at three different frequencies was then used to investigate possible alterations in the power spectral density (PSD) of low-frequency oscillations. For each group, the average PSD was determined for each brain region and a nonparametric test was performed to determine the difference in power between the two groups. Significantly reduced inter-hemispheric functional connectivity between the left and right PMC was observed in patients compared with controls (P<0.05). We also found significantly decreased PSD in patients compared to that in controls, in all three frequency bands (low: 0.01–0.02 Hz; middle: 0.02–0.06 Hz; and high: 0.06–0.1 Hz), at three key motor regions. These findings suggest that in asymptomatic patients with brain tumors located in eloquent regions, inter-hemispheric connection may be more vulnerable. A comparison of the two approaches indicated that power spectral analysis is more sensitive than functional connectivity analysis for identifying the neurological abnormalities underlying motor function plasticity induced by slow-growing tumors. PMID:24806463

  17. Retinal microvascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study

    PubMed Central

    Cheung, Ning; Mosley, Thomas; Islam, Amirul; Kawasaki, Ryo; Sharrett, A. Richey; Klein, Ronald; Coker, Laura H.; Knopman, David S.; Shibata, Dean K.; Catellier, Diane

    2010-01-01

    Silent brain infarct and white matter lesions are common radiological findings associated with the risk of clinical stroke and dementia; however, our understanding of their underlying pathophysiology and risk factors remains limited. This study aimed to determine whether assessment of retinal microvascular abnormalities could provide prognostic information regarding the risk of brain infarct and white matter lesions on magnetic resonance imaging. This study is based on a subset of 810 middle-aged persons without clinical stroke or baseline magnetic resonance imaging infarct enrolled in the Atherosclerosis Risk in Communities Brain Magnetic Resonance Imaging Study, a prospective, population-based study. Participants had a baseline magnetic resonance imaging brain examination and retinal photography in 1993–1995, and returned for a repeat magnetic resonance imaging examination in 2004–2006. Magnetic resonance images were graded for presence of any cerebral infarct, infarct with lacunar characteristics and white matter lesions according to standardized protocols. Retinal photographs were graded for presence of retinopathy lesions and retinal arteriolar abnormalities following a standardized protocol. Over a median follow-up of 10.5 years, 164 (20.2%) participants developed cerebral infarct, 131 (16.2%) developed lacunar infarct, 182 (24.2%) developed new white matter lesions and 49 (6.1%) had evidence of white matter lesion progression. After adjusting for age, gender, race, cardiovascular risk factors and carotid intima-media thickness, retinopathy was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval 1.42–5.60) and lacunar infarct (odds ratio 3.19; 95% confidence interval: 1.56–6.50). Retinal arteriovenous nicking was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval: 1.66–4.76), lacunar infarct (odds ratio 2.48; 95% confidence interval: 1.39–4.40) and white matter lesion incidence (odds

  18. Abnormal structural connectivity in the brain networks of children with hydrocephalus

    PubMed Central

    Yuan, Weihong; Holland, Scott K.; Shimony, Joshua S.; Altaye, Mekibib; Mangano, Francesco T.; Limbrick, David D.; Jones, Blaise V.; Nash, Tiffany; Rajagopal, Akila; Simpson, Sarah; Ragan, Dustin; McKinstry, Robert C.

    2015-01-01

    Increased intracranial pressure and ventriculomegaly in children with hydrocephalus are known to have adverse effects on white matter structure. This study seeks to investigate the impact of hydrocephalus on topological features of brain networks in children. The goal was to investigate structural network connectivity, at both global and regional levels, in the brains in children with hydrocephalus using graph theory analysis and diffusion tensor tractography. Three groups of children were included in the study (29 normally developing controls, 9 preoperative hydrocephalus patients, and 17 postoperative hydrocephalus patients). Graph theory analysis was applied to calculate the global network measures including small-worldness, normalized clustering coefficients, normalized characteristic path length, global efficiency, and modularity. Abnormalities in regional network parameters, including nodal degree, local efficiency, clustering coefficient, and betweenness centrality, were also compared between the two patients groups (separately) and the controls using two tailed t-test at significance level of p < 0.05 (corrected for multiple comparison). Children with hydrocephalus in both the preoperative and postoperative groups were found to have significantly lower small-worldness and lower normalized clustering coefficient than controls. Children with hydrocephalus in the postoperative group were also found to have significantly lower normalized characteristic path length and lower modularity. At regional level, significant group differences (or differences at trend level) in regional network measures were found between hydrocephalus patients and the controls in a series of brain regions including the medial occipital gyrus, medial frontal gyrus, thalamus, cingulate gyrus, lingual gyrus, rectal gyrus, caudate, cuneus, and insular. Our data showed that structural connectivity analysis using graph theory and diffusion tensor tractography is sensitive to detect

  19. Abnormal structural connectivity in the brain networks of children with hydrocephalus.

    PubMed

    Yuan, Weihong; Holland, Scott K; Shimony, Joshua S; Altaye, Mekibib; Mangano, Francesco T; Limbrick, David D; Jones, Blaise V; Nash, Tiffany; Rajagopal, Akila; Simpson, Sarah; Ragan, Dustin; McKinstry, Robert C

    2015-01-01

    Increased intracranial pressure and ventriculomegaly in children with hydrocephalus are known to have adverse effects on white matter structure. This study seeks to investigate the impact of hydrocephalus on topological features of brain networks in children. The goal was to investigate structural network connectivity, at both global and regional levels, in the brains in children with hydrocephalus using graph theory analysis and diffusion tensor tractography. Three groups of children were included in the study (29 normally developing controls, 9 preoperative hydrocephalus patients, and 17 postoperative hydrocephalus patients). Graph theory analysis was applied to calculate the global network measures including small-worldness, normalized clustering coefficients, normalized characteristic path length, global efficiency, and modularity. Abnormalities in regional network parameters, including nodal degree, local efficiency, clustering coefficient, and betweenness centrality, were also compared between the two patients groups (separately) and the controls using two tailed t-test at significance level of p < 0.05 (corrected for multiple comparison). Children with hydrocephalus in both the preoperative and postoperative groups were found to have significantly lower small-worldness and lower normalized clustering coefficient than controls. Children with hydrocephalus in the postoperative group were also found to have significantly lower normalized characteristic path length and lower modularity. At regional level, significant group differences (or differences at trend level) in regional network measures were found between hydrocephalus patients and the controls in a series of brain regions including the medial occipital gyrus, medial frontal gyrus, thalamus, cingulate gyrus, lingual gyrus, rectal gyrus, caudate, cuneus, and insular. Our data showed that structural connectivity analysis using graph theory and diffusion tensor tractography is sensitive to detect

  20. Abnormal patterns of displacement activities: a review and reinterpretation.

    PubMed

    Anselme, Patrick

    2008-09-01

    A series of important theoretical contributions flourished in the years 1950-1970 about displacement activities -- those 'out-of-context' actions expressed by organisms in stressful situations. Nothing really new has appeared thereafter. Although the models address different issues, such as causal factors of displacement, it appears obvious that they do not provide a unified (coherent) approach; they often explain the same phenomena using very different means and turn out to be contradictory on several points. In addition, some problems currently remain unsolved, especially concerning the fact that displacement activities exhibit 'abnormalities' of expression in comparison with the same activities performed in usual context. Each model is here described and criticized in order to evaluate its explanatory power and allow the identification of specific limits. A new, integrative model -- the Anticipatory Dynamics Model (or ADM) -- then attempts to overcome the failures of previous models. The ADM suggests that abnormal patterns of displacement activities result from attentional interference caused by a thwarting experience or conflicting motivations. At least one theoretical prediction of the ADM can be differentiated from that of any other model. PMID:18554824

  1. Structural abnormalities of the brain in schizophrenia: sex differences in the Cantabria First Episode of Schizophrenia Study.

    PubMed

    Vázquez-Barquero, J L; Cuesta Núñez, M J; Quintana Pando, F; de la Varga, M; Herrera Castanedo, S; Dunn, G

    1995-11-01

    This paper examines structural brain abnormalities, as evaluated by the CT scan, in first episodes of schizophrenia and their association with sociodemographic, diagnostic and clinical variables. The investigation included all patients with a first episode of schizophrenia who, over a 2-year period, made contact with any of the public mental health services of the Autonomous Region of Cantabria in Northern Spain. Diagnostic and clinical characteristics were evaluated through the use of the Spanish version of the Present State Examination (PSE-9) and the Scales for the Assessment of Positive and Negative Symptoms (SANS and SAPS respectively). The study demonstrated the presence of structural brain abnormalities in this sample of first episode schizophrenics. These abnormalities were mainly expressed in the presence of larger VBR for schizophrenic patients than in the controls, these findings being more marked in women than in men. We failed to reveal, however, any evidence of an association of these brain abnormalities with diagnostic or clinical characteristics. PMID:8637954

  2. Neural activation abnormalities during self-referential processing in schizophrenia: an fMRI study.

    PubMed

    Liu, Jiacheng; Corbera, Silvia; Wexler, Bruce Edward

    2014-06-30

    Impairments in self-awareness contribute to disability in schizophrenia. Studies have revealed activation abnormalities in schizophrenia in cortical midline structures associated with self-reference. We used functional magnetic resonance imaging to compare activation throughout the brain in people with schizophrenia and healthy controls (Kelly et al., 2002) while they indicated whether trait adjectives described attributes of themselves, their mother or a former president of the United States. Blood oxygenation level dependent signal in each condition was compared to resting fixation. Patients were less likely and slower to endorse positive self-attributes, and more likely and quicker to endorse negative self-attributes than controls. Activation abnormalities reported previously in cortical midline structures were again noted. In addition, patients showed greater signal increases in frontal, temporal gyri and insula, and smaller signal decreases in posterior regions than healthy controls when thinking about themselves. Group differences were less evident when subjects were thinking about their mothers and tended to go in the opposite direction when thinking about a president. Many of the areas showing abnormality have been shown in other studies to differ between patients and controls in structure and with other activation paradigms. We suggest that general neuropathology in schizophrenia alters the neural system configurations associated with self-representation. PMID:24795158

  3. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease

    PubMed Central

    Tian, Junzhang; Dong, Jianwei; He, Jinlong; Zhan, Wenfeng; Xu, Lijuan; Xu, Yikai; Jiang, Guihua

    2016-01-01

    Purpose To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD) and examine the relationship between brain microstructure and physiological indictors in the disease. Materials and Methods Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18–61 years) and 40 age- and gender-matched healthy controls (HCs, 32 men, 22–58 years). A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients. Results Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM) but also gray matter (GM) regions, as characterized by decreased fractional anisotropy (FA) and increased mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part) in the patients. Conclusion Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease. PMID:27227649

  4. Abnormal White Matter Blood-Oxygen-Level-Dependent Signals in Chronic Mild Traumatic Brain Injury.

    PubMed

    Astafiev, Serguei V; Shulman, Gordon L; Metcalf, Nicholas V; Rengachary, Jennifer; MacDonald, Christine L; Harrington, Deborah L; Maruta, Jun; Shimony, Joshua S; Ghajar, Jamshid; Diwakar, Mithun; Huang, Ming-Xiong; Lee, Roland R; Corbetta, Maurizio

    2015-08-15

    Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI. PMID:25758167

  5. Effects of hyperbaric oxygen on eye tracking abnormalities in males after mild traumatic brain injury.

    PubMed

    Cifu, David X; Hoke, Kathy W; Wetzel, Paul A; Wares, Joanna R; Gitchel, George; Carne, William

    2014-01-01

    The effects of hyperbaric oxygen (HBO2) on eye movement abnormalities in 60 military servicemembers with at least one mild traumatic brain injury (TBI) from combat were examined in a single-center, randomized, double-blind, sham-controlled, prospective study at the Naval Medicine Operational Training Center. During the 10 wk of the study, each subject was delivered a series of 40, once a day, hyperbaric chamber compressions at a pressure of 2.0 atmospheres absolute (ATA). At each session, subjects breathed one of three preassigned oxygen fractions (10.5%, 75%, or 100%) for 1 h, resulting in an oxygen exposure equivalent to breathing either surface air, 100% oxygen at 1.5 ATA, or 100% oxygen at 2.0 ATA, respectively. Using a standardized, validated, computerized eye tracking protocol, fixation, saccades, and smooth pursuit eye movements were measured just prior to intervention and immediately postintervention. Between and within groups testing of pre- and postintervention means revealed no significant differences on eye movement abnormalities and no significant main effect for HBO2 at either 1.5 ATA or 2.0 ATA equivalent compared with the sham-control. This study demonstrated that neither 1.5 nor 2.0 ATA equivalent HBO2 had an effect on postconcussive eye movement abnormalities after mild TBI when compared with a sham-control. PMID:25436771

  6. Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis.

    PubMed

    Plumb, Jonnie; McQuaid, Stephen; Mirakhur, Meenakshi; Kirk, John

    2002-04-01

    Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated. We investigated the possible involvement of interendothelial tight junctions (TJ) by examining the expression of TJ proteins (occludin and ZO-1 ) in blood vessels in active MS lesions from 8 cases of MS and in normal-appearing white (NAWM) matter from 6 cases. Blood vessels (10-50 per frozen section) were scanned using confocal laser scanning microscopy to acquire datasets for analysis. TJ abnormalities manifested as beading, interruption, absence or diffuse cytoplasmic localization of fluorescence, or separation of junctions (putative opening) were frequent (affecting 40% of vessels) in oil-red-O-positive active plaques but less frequent in NAWM (15%), and in normal (< 2%) and neurological controls (6%). Putatively "open" junctions were seen in vessels in active lesions and in microscopically inflamed vessels in NAWM. Dual fluorescence revealed abnormal TJs in vessels with pre-mortem serum protein leakage. Abnormal or open TJs, associated with inflammation may contribute to BBB leakage in enhancing MRI lesions and may also be involved in subtle leakage in non-enhancing focal and diffuse lesions in NAWM. BBB disruption due to tight junctional pathology should be regarded as a significant form of tissue injury in MS, alongside demyelination and axonopathy. PMID:11958369

  7. The nature of white matter abnormalities in blast-related mild traumatic brain injury

    PubMed Central

    Hayes, Jasmeet P.; Miller, Danielle R.; Lafleche, Ginette; Salat, David H.; Verfaellie, Mieke

    2015-01-01

    Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having

  8. The nature of white matter abnormalities in blast-related mild traumatic brain injury.

    PubMed

    Hayes, Jasmeet P; Miller, Danielle R; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

    2015-01-01

    Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having

  9. Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

    PubMed Central

    Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

    2013-01-01

    Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

  10. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

    PubMed Central

    Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

    2016-01-01

    Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

  11. Multicenter Study of Brain Volume Abnormalities in Children and Adolescent-Onset Psychosis

    PubMed Central

    Reig, Santiago; Parellada, Mara; Castro-Fornieles, Josefina; Janssen, Joost; Moreno, Dolores; Baeza, Inmaculada; Bargalló, Nuria; González-Pinto, Ana; Graell, Montserrat; Ortuño, Felipe; Otero, Soraya; Arango, Celso; Desco, Manuel

    2011-01-01

    The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of “schizophrenia” or “other psychosis” showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents. PMID:20478821

  12. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice.

    PubMed

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-04-14

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  13. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice

    PubMed Central

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-01-01

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  14. Multidimensional morphometric 3D MRI analyses for detecting brain abnormalities in children: impact of control population.

    PubMed

    Wilke, Marko; Rose, Douglas F; Holland, Scott K; Leach, James L

    2014-07-01

    Automated morphometric approaches are used to detect epileptogenic structural abnormalities in 3D MR images in adults, using the variance of a control population to obtain z-score maps in an individual patient. Due to the substantial changes the developing human brain undergoes, performing such analyses in children is challenging. This study investigated six features derived from high-resolution T1 datasets in four groups: normal children (1.5T or 3T data), normal clinical scans (3T data), and patients with structural brain lesions (3T data), with each n = 10. Normative control data were obtained from the NIH study on normal brain development (n = 401). We show that control group size substantially influences the captured variance, directly impacting the patient's z-scores. Interestingly, matching on gender does not seem to be beneficial, which was unexpected. Using data obtained at higher field scanners produces slightly different base rates of suprathreshold voxels, as does using clinically derived normal studies, suggesting a subtle but systematic effect of both factors. Two approaches for controlling suprathreshold voxels in a multidimensional approach (combining features and requiring a minimum cluster size) were shown to be substantial and effective in reducing this number. Finally, specific strengths and limitations of such an approach could be demonstrated in individual cases. PMID:25050423

  15. Oseltamivir reduces hippocampal abnormal EEG activities after a virus infection (influenza) in isoflurane-anesthetized rats

    PubMed Central

    Cissé, Youssouf; Inoue, Isao; Kido, Hiroshi

    2012-01-01

    Background Oseltamivir phosphate (OP, Tamiflu®) is a widely used drug in the treatment of influenza with fever. However, case reports have associated OP intake with sudden abnormal behaviors. In rats infected by the influenza A virus (IAV), the electroencephalogram (EEG) displayed abnormal high-voltage amplitudes with spikes and theta oscillations at a core temperature of 39.9°C to 41°C. Until now, there has been no information describing the effect of OP on intact brain hippocampal activity of IAV-infected animals during hyperthermia. Objective The aim of the present study was to examine the effect of OP on abnormal EEG activities in the hippocampus using the rat model of influenza-associated encephalopathy. Methods Male Wistar rats aged 3 to 4 weeks were used for the study. Influenza A/WSN/33 strain (1 × 105 plaque forming unit in PBS, 60 µL) was applied intranasally to the rats. To characterize OP effects on the IAV-infected rats, EEG activity was studied more particularly in isoflurane-anesthetized IAV-infected rats during hyperthermia. Results We found that the hippocampal EEG of the OP-administered (10 mg/kg) IAV-infected rats showed significant reduction of the high-voltage amplitudes and spikes, but the theta oscillations, which had been observed only at >40°C in OP non-administered rats, appeared at 38°C core temperature. Atropine (30 mg/kg) blocked the theta oscillations. Conclusion Our data suggest that OP efficiently reduces the abnormal EEG activities after IAV infection during hyperthermia. However, OP administration may stimulate ACh release in rats at normal core temperature.

  16. Neonatal brain abnormalities associated with autism spectrum disorder in children born very preterm.

    PubMed

    Ure, Alexandra M; Treyvaud, Karli; Thompson, Deanne K; Pascoe, Leona; Roberts, Gehan; Lee, Katherine J; Seal, Marc L; Northam, Elisabeth; Cheong, Jeanie L; Hunt, Rod W; Inder, Terrie; Doyle, Lex W; Anderson, Peter J

    2016-05-01

    Very preterm (VP) survivors are at increased risk of autism spectrum disorder (ASD) compared with term-born children. This study explored whether neonatal magnetic resonance (MR) brain features differed in VP children with and without ASD at 7 years. One hundred and seventy-two VP children (<30 weeks' gestation or <1250 g birth weight) underwent structural brain MR scans at term equivalent age (TEA; 40 weeks' gestation ±2 weeks) and were assessed for ASD at 7 years of age. The presence and severity of white matter, cortical gray matter, deep nuclear gray matter, and cerebellar abnormalities were assessed, and total and regional brain volumes were measured. ASD was diagnosed using a standardized parent report diagnostic interview and confirmed via an independent assessment. Eight VP children (4.7%) were diagnosed with ASD. Children with ASD had more cystic lesions in the cortical white matter at TEA compared with those without ASD (odds ratio [OR] 8.7, 95% confidence interval [CI] 1.5, 51.3, P = 0.02). There was also some evidence for smaller cerebellar volumes in children with ASD compared with those without ASD (OR = 0.82, CI = 0.66, 1.00, P = 0.06). Overall, the results suggest that VP children with ASD have different brain structure in the neonatal period compared with those who do not have ASD. Autism Res 2016, 9: 543-552. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID:26442616

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

    PubMed Central

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

    2015-01-01

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

  18. Working Memory Encoding and Maintenance Deficits in Schizophrenia: Neural Evidence for Activation and Deactivation Abnormalities

    PubMed Central

    Anticevic, Alan; Repovs, Grega; Barch, Deanna M.

    2013-01-01

    Substantial evidence implicates working memory (WM) as a core deficit in schizophrenia (SCZ), purportedly due to primary deficits in dorsolateral prefrontal cortex functioning. Recent findings suggest that SCZ is also associated with abnormalities in suppression of certain regions during cognitive engagement—namely the default mode system—that may further contribute to WM pathology. However, no study has systematically examined activation and suppression abnormalities across both encoding and maintenance phases of WM in SCZ. Twenty-eight patients and 24 demographically matched healthy subjects underwent functional magnetic resonance imaging at 3T while performing a delayed match-to-sample WM task. Groups were accuracy matched to rule out performance effects. Encoding load was identical across subjects to facilitate comparisons across WM phases. We examined activation differences using an assumed model approach at the whole-brain level and within meta-analytically defined WM areas. Despite matched performance, we found regions showing less recruitment during encoding and maintenance for SCZ subjects. Furthermore, we identified 2 areas closely matching the default system, which SCZ subjects failed to deactivate across WM phases. Lastly, activation in prefrontal regions predicted the degree of deactivation for healthy but not SCZ subjects. Current results replicate and extend prefrontal recruitment abnormalities across WM phases in SCZ. Results also indicate deactivation abnormalities across WM phases, possibly due to inefficient prefrontal recruitment. Such regional deactivation may be critical for suppressing sources of interference during WM trace formation. Thus, deactivation deficits may constitute an additional source of impairments, which needs to be further characterized for a complete understanding of WM pathology in SCZ. PMID:21914644

  19. Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and molecular aspects.

    PubMed

    Fernandes, Marilyse B L; Maximino, Luciana P; Perosa, Gimol B; Abramides, Dagma V M; Passos-Bueno, Maria Rita; Yacubian-Fernandes, Adriano

    2016-06-01

    Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain-of-function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain-of-function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940-2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS). © 2016 Wiley Periodicals, Inc. PMID:27028366

  20. Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP.

    PubMed

    Hu, Bo; Arpag, Sezgi; Zhang, Xuebao; Möbius, Wiebke; Werner, Hauke; Sosinsky, Gina; Ellisman, Mark; Zhang, Yang; Hamilton, Audra; Chernoff, Jonathan; Li, Jun

    2016-09-01

    Schwann cells in the peripheral nervous systems extend their membranes to wrap axons concentrically and form the insulating sheath, called myelin. The spaces between layers of myelin are sealed by myelin junctions. This tight insulation enables rapid conduction of electric impulses (action potentials) through axons. Demyelination (stripping off the insulating sheath) has been widely regarded as one of the most important mechanisms altering the action potential propagation in many neurological diseases. However, the effective nerve conduction is also thought to require a proper myelin seal through myelin junctions such as tight junctions and adherens junctions. In the present study, we have demonstrated the disruption of myelin junctions in a mouse model (Pmp22+/-) of hereditary neuropathy with liability to pressure palsies (HNPP) with heterozygous deletion of Pmp22 gene. We observed a robust increase of F-actin in Pmp22+/- nerve regions where myelin junctions were disrupted, leading to increased myelin permeability. These abnormalities were present long before segmental demyelination at the late phase of Pmp22+/- mice. Moreover, the increase of F-actin levels correlated with an enhanced activity of p21-activated kinase (PAK1), a molecule known to regulate actin polymerization. Pharmacological inhibition of PAK normalized levels of F-actin, and completely prevented the progression of the myelin junction disruption and nerve conduction failure in Pmp22+/- mice. Our findings explain how abnormal myelin permeability is caused in HNPP, leading to impaired action potential propagation in the absence of demyelination. We call it "functional demyelination", a novel mechanism upstream to the actual stripping of myelin that is relevant to many demyelinating diseases. This observation also provides a potential therapeutic approach for HNPP. PMID:27583434

  1. Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia.

    PubMed

    Belton, Emma; Salmond, Claire H; Watkins, Kate E; Vargha-Khadem, Faraneh; Gadian, David G

    2003-03-01

    The KE family is a large three-generational pedigree in which half of the members suffer from a verbal and orofacial dyspraxia in association with a point mutation in the FOXP2 gene. This report extends previous voxel-based morphometric analyses of magnetic resonance imaging (MRI) scans (Watkins et al. [2002] Brain 125:465-478) using a bilateral conjunction analysis. This searches specifically for areas of grey matter density that differ bilaterally in the affected members compared with both matched controls and the unaffected family members. 3-D T1-weighted MRI datasets of 17 family members (10 affected, 7 unaffected) and matched controls were compared. The most significant findings were reduced grey matter density bilaterally in the caudate nucleus, the cerebellum, and the left and right inferior frontal gyrus in the affected members. In addition, increased grey matter density was found bilaterally in the planum temporale. These results confirm that a point mutation in FOXP2 is associated with several bilateral grey matter abnormalities in both motor and language related regions. The results also demonstrate the advantages of using a conjunction analysis when bilateral abnormalities are suspected. PMID:12599277

  2. Mathematical Difficulties and White Matter Abnormalities in Subacute Pediatric Mild Traumatic Brain Injury.

    PubMed

    Van Beek, Leen; Ghesquière, Pol; Lagae, Lieven; De Smedt, Bert

    2015-10-15

    Mathematical difficulties have been documented following pediatric mild traumatic brain injury (mTBI), yet a precise characterization of these impairments and their neural correlates is currently unavailable. We aimed to characterize these impairments by comparing behavioral and neuroimaging (i.e., diffusion tensor imaging [DTI]) outcomes from children with subacute mTBI to typically-developing controls. Twenty subacute pediatric mTBI patients and 20 well-matched controls underwent cognitive assessment and DTI examination. DTI tractography was used to detect white matter abnormalities in the corpus callosum (CC) and superior and inferior longitudinal fasciculi; these tracts are involved in mathematical performance and they are often damaged after mTBI. Behavioral results revealed that children with mTBI performed significantly more poorly on rapid apprehension of small numbers of objects (or "subitizing"), processing of non-symbolic numerosities, and procedural problem solving. These group differences were explained by differences in visuospatial working memory, which suggests that the observed mathematical difficulties may be a consequence of impairments in visuospatial abilities. DTI analysis revealed subtle group differences in the CC genu and splenium (i.e., higher fractional anisotropy and lower mean and radial diffusivity in children with mTBI) but the observed white matter abnormalities of the CC were not significantly associated with the observed mathematical difficulties in the mTBI patients. PMID:25915107

  3. C21orf5, a human candidate gene for brain abnormalities and mental retardation in Down syndrome.

    PubMed

    Rachidi, M; Lopes, C; Delezoide, A-L; Delabar, J M

    2006-01-01

    Mental retardation represents the more invalidating pathological aspect of trisomy 21 and has a hard impact on public health. The dosage imbalance of chromosome 21 genes could be the cause of neurological alterations and mental retardation seen in Down syndrome. We studied C21orf5 that we have demonstrated to be overexpressed in Down syndrome tissues, as a candidate gene for trisomy 21. A new optical technology (Rachidi et al., 2000) was used to compare signal intensity and cell density in presumptive embryonic brain compartments, at their boundaries and in higher specialized brain centres during fetal lifespan. We showed a developmentally regulated transcriptional activity of C21orf5 and a regional and cellular specific distribution of gene transcripts during human embryonic and fetal development. A wide but differential expression was detected in the nervous system during embryogenesis with a relatively lower level in the forebrain than in the midbrain and hindbrain and the highest transcription intensity in the future cerebellum. This developmentally regulated expression is maintained during post-embryogenesis and evolves selectively in fetal cerebral, hippocampal and cerebellar areas. Differential and cellular specificity were detected in hippocampus with higher C21orf5 mRNA level in the pyramidal cells compared to granular cells of the dentate gyrus. The expression pattern detected in cortical and cerebellar structures correlates well to the altered cortical lamination and to the lower size of the cerebellum observed in Down syndrome patients. In addition, the patterned differential expression detected in the medial temporal-lobe system, including hippocampal formation and perirhinal cortex, working as control centres of the memory circuits and involved in cognitive processes and memory storage, also corresponds to abnormal brain regions seen in Down syndrome patients. The C21orf5 selective expression in the key brain structures for learning and memory

  4. Right Brain Activities to Improve Analytical Thinking.

    ERIC Educational Resources Information Center

    Lynch, Marion E.

    Schools tend to have a built-in bias toward left brain activities (tasks that are linear and sequential in nature), so the introduction of right brain activities (functions related to music, rhythm, images, color, imagination, daydreaming, dimensions) brings a balance into the classroom and helps those students who may be right brain oriented. To…

  5. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    SciTech Connect

    Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  6. Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia.

    PubMed

    Schiffer, Boris; Peschel, Thomas; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Krueger, Tillmann H C

    2007-11-01

    Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive-compulsive spectrum disorders. PMID:16876824

  7. Docosahexaenoic acid reduces ER stress and abnormal protein accumulation and improves neuronal function following traumatic brain injury.

    PubMed

    Begum, Gulnaz; Yan, Hong Q; Li, Liaoliao; Singh, Amneet; Dixon, C Edward; Sun, Dandan

    2014-03-01

    In this study, we investigated the development of endoplasmic reticulum (ER) stress after traumatic brain injury (TBI) and the efficacy of post-TBI administration of docosahexaenoic acid (DHA) in reducing ER stress. TBI was induced by cortical contusion injury in Sprague-Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered intraperitoneally at 5 min after TBI, followed by a daily dose for 3-21 d. TBI triggered sustained expression of the ER stress marker proteins including phosphorylated eukaryotic initiation factor-2α, activating transcription factor 4, inositol requiring kinase 1, and C/EBP homologous protein in the ipsilateral cortex at 3-21 d after TBI. The prolonged ER stress was accompanied with an accumulation of abnormal ubiquitin aggregates and increased expression of amyloid precursor protein (APP) and phosphorylated tau (p-Tau) in the frontal cortex after TBI. The ER stress marker proteins were colocalized with APP accumulation in the soma. Interestingly, administration of DHA attenuated all ER stress marker proteins and reduced the accumulation of both ubiquitinated proteins and APP/p-Tau proteins. In addition, the DHA-treated animals exhibited early recovery of their sensorimotor function after TBI. In summary, our study demonstrated that TBI induces a prolonged ER stress, which is positively correlated with abnormal APP accumulation. The sustained ER stress may play a role in chronic neuronal damage after TBI. Our findings illustrate that post-TBI administration of DHA has therapeutic potentials in reducing ER stress, abnormal protein accumulation, and neurological deficits. PMID:24599472

  8. Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia

    PubMed Central

    Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

    2016-01-01

    Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states. PMID:26708106

  9. Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

    PubMed

    Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

    2016-07-01

    Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states. PMID:26708106

  10. Abnormal fast activity in infancy with paroxysmal downwards gaze.

    PubMed

    Yoshinaga, Harumi; Kobayashi, Katsuhiro; Endo, Fumika; Ishizaki, Yumiko; Wakai, Mari; Ohtsuka, Yoko

    2009-06-01

    We report here on 8 infants who showed paroxysmal downwards gaze (PDG). The time of initial appearance of PDG ranged from one month to five months (mean: 2.7 months) of corrected age. Seven out of eight patients showed interictal spikes in EEG, so they were started on prophylactic therapy with antiepileptic drugs. In five of the eight patients, PDG ceased, either spontaneously or with antiepileptic drug treatment, by four to eight months of corrected age. Six out of eight patients showed localized spikes and peculiar abnormal fast activity (AFA) in the occipital area and five of these patients later developed West syndrome. These AFA were observed on EEGs recorded at the time of initial PDG appearance, before hypsarrhythmia was observed and before tonic spasms appeared. We were able to exclude the possibility that PDG was a subtle epileptic seizure by confirming the temporal discordance between individual episodes of PDG and AFA with video-EEG monitoring. Yet topographic data showed that AFA in these patients was characteristically located in the occipital area, with a distribution similar to that of the fast activity which accompanied the tonic spasms that later developed in these patients. As a risk factor for developing WS, we propose the clinical symptom of PDG with characteristic occipital AFA visible in the EEG, both of which represent damage to the occipital region including the optic radiation. PMID:18804928

  11. Cross-Sectional and Longitudinal Abnormalities in Brain Structure in Children with Severe Mood Dysregulation or Bipolar Disorder

    ERIC Educational Resources Information Center

    Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

    2012-01-01

    Background: There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time.…

  12. Brain Gray Matter Abnormalities in First-Episode, Treatment-Naive Children with Obsessive-Compulsive Disorder

    PubMed Central

    Cheng, Bochao; Cai, Wu; Wang, Xiuli; Lei, Du; Guo, Yingkun; Yang, Xun; Wu, Qizhu; Gong, Jianping; Gong, Qiyong; Ning, Gang

    2016-01-01

    Although several magnetic resonance imaging (MRI) studies have been conducted in children with obsessive-compulsive disorder (OCD), the brain structural abnormalities in OCD, especially in children, are not yet well characterized. We aimed to identify gray matter (GM) abnormalities in the early stage of pediatric OCD and examine the relationship between these structural abnormalities with clinical characteristics. Examinations of 30 first-episode, treatment-naive pediatric OCD patients without any comorbidities and 30 matched healthy controls (HCs) were performed with 3.0 T magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) following Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL) was used to conduct voxel-wise tests for group differences in regional gray matter volume (GMV). Compared to HCs, the patient group exhibited more GMV in the bilateral putamen and left orbitofrontal cortex (OFC) and less GMV in the left inferior parietal lobule (IPL). The GMV alternation in the right putamen of OCD patients was positively correlated with Hamilton Anxiety Rating Scale (HAM-A) scores, while the GMV alternation in the left IPL exhibited a trend to negatively correlate with HAM-A scores. Our current results suggest that the GM abnormalities were defined in the early stage of pediatric OCD. Moreover, these findings provided further evidence of brain GM abnormalities that are not only present in the classical fronto–striatal–thalamic circuit but also in the default mode network (DMN), which may represent the interaction of abnormally functional organization of both network in pediatric OCD. PMID:27445736

  13. Brain Gray Matter Abnormalities in First-Episode, Treatment-Naive Children with Obsessive-Compulsive Disorder.

    PubMed

    Cheng, Bochao; Cai, Wu; Wang, Xiuli; Lei, Du; Guo, Yingkun; Yang, Xun; Wu, Qizhu; Gong, Jianping; Gong, Qiyong; Ning, Gang

    2016-01-01

    Although several magnetic resonance imaging (MRI) studies have been conducted in children with obsessive-compulsive disorder (OCD), the brain structural abnormalities in OCD, especially in children, are not yet well characterized. We aimed to identify gray matter (GM) abnormalities in the early stage of pediatric OCD and examine the relationship between these structural abnormalities with clinical characteristics. Examinations of 30 first-episode, treatment-naive pediatric OCD patients without any comorbidities and 30 matched healthy controls (HCs) were performed with 3.0 T magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) following Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL) was used to conduct voxel-wise tests for group differences in regional gray matter volume (GMV). Compared to HCs, the patient group exhibited more GMV in the bilateral putamen and left orbitofrontal cortex (OFC) and less GMV in the left inferior parietal lobule (IPL). The GMV alternation in the right putamen of OCD patients was positively correlated with Hamilton Anxiety Rating Scale (HAM-A) scores, while the GMV alternation in the left IPL exhibited a trend to negatively correlate with HAM-A scores. Our current results suggest that the GM abnormalities were defined in the early stage of pediatric OCD. Moreover, these findings provided further evidence of brain GM abnormalities that are not only present in the classical fronto-striatal-thalamic circuit but also in the default mode network (DMN), which may represent the interaction of abnormally functional organization of both network in pediatric OCD. PMID:27445736

  14. Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities

    PubMed Central

    Lyons, W. Ernest; Mamounas, Laura A.; Ricaurte, George A.; Coppola, Vincenzo; Reid, Susan W.; Bora, Susan H.; Wihler, Cornelia; Koliatsos, Vassilis E.; Tessarollo, Lino

    1999-01-01

    Brain-derived neurotrophic factor (BDNF) has trophic effects on serotonergic (5-HT) neurons in the central nervous system. However, the role of endogenous BDNF in the development and function of these neurons has not been established in vivo because of the early postnatal lethality of BDNF null mice. In the present study, we use heterozygous BDNF+/− mice that have a normal life span and show that these animals develop enhanced intermale aggressiveness and hyperphagia accompanied by significant weight gain in early adulthood; these behavioral abnormalities are known to correlate with 5-HT dysfunction. Forebrain 5-HT levels and fiber density in BDNF+/− mice are normal at an early age but undergo premature age-associated decrements. However, young adult BDNF+/− mice show a blunted c-fos induction by the specific serotonin releaser-uptake inhibitor dexfenfluramine and alterations in the expression of several 5-HT receptors in the cortex, hippocampus, and hypothalamus. The heightened aggressiveness can be ameliorated by the selective serotonin reuptake inhibitor fluoxetine. Our results indicate that endogenous BDNF is critical for the normal development and function of central 5-HT neurons and for the elaboration of behaviors that depend on these nerve cells. Therefore, BDNF+/− mice may provide a useful model to study human psychiatric disorders attributed to dysfunction of serotonergic neurons. PMID:10611369

  15. Brain structural abnormalities in patients with major depression with or without generalized anxiety disorder comorbidity.

    PubMed

    Canu, Elisa; Kostić, Milutin; Agosta, Federica; Munjiza, Ana; Ferraro, Pilar M; Pesic, Danilo; Copetti, Massimiliano; Peljto, Amir; Lecic Tosevski, Dusica; Filippi, Massimo

    2015-05-01

    An overlap frequently occurs between major depression disorder (MDD) and generalized anxiety disorder (GAD). Aim of this study was to assess cortical and white matter (WM) alterations in MDD patients with or without GAD comorbidity. Seventy-one MDD patients and 71 controls were recruited. All subjects underwent T1-weighted and diffusion tensor (DT)/MRI. MRI metrics of cortical thickness and WM integrity were obtained from atlas-based cortical regions and the interhemispheric and major long association WM tracts. Between-group MRI comparisons and multiple regressions with clinical scale scores were performed. Compared to controls, both MDD and MDD-GAD patients showed a cortical thinning of the middle frontal cortex bilaterally, left medial frontal gyrus and frontal pole. Compared to controls and MDD patients, MDD-GAD cases also showed a thinning of the right medial orbitofrontal and fusiform gyri, and left temporal pole and lateral occipital cortices. Compared to controls, MDD patients showed DT MRI abnormalities of the right parahippocampal tract and superior longitudinal fasciculus bilaterally, while no WM alterations were found in MDD-GAD. In all patients, brain abnormalities were related with symptom severity. MDD and MDD-GAD share a common pattern of cortical alterations located in the frontal regions. However, while both the cortex and WM integrity are affected in MDD, only the former is affected in MDD-GAD. These findings support the notion of MDD-GAD as a distinct clinical entity, providing insights into patient vulnerability for specific networks as well as into patient resilience factors reflected by the integrity of other cerebral circuits. PMID:25794861

  16. Sensory neuron-specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis

    NASA Astrophysics Data System (ADS)

    Black, Joel A.; Dib-Hajj, Sulayman; Baker, David; Newcombe, Jia; Cuzner, M. Louise; Waxman, Stephen G.

    2000-10-01

    Clinical abnormalities in multiple sclerosis (MS) have classically been considered to be caused by demyelination and/or axonal degeneration; the possibility of molecular changes in neurons, such as the deployment of abnormal repertoires of ion channels that would alter neuronal electrogenic properties, has not been considered. Sensory Neuron-Specific sodium channel SNS displays a depolarized voltage dependence, slower activation and inactivation kinetics, and more rapid recovery from inactivation than classical "fast" sodium channels. SNS is selectively expressed in spinal sensory and trigeminal ganglion neurons within the peripheral nervous system and is not expressed within the normal brain. Here we show that sodium channel SNS mRNA and protein, which are not present within the cerebellum of control mice, are expressed within cerebellar Purkinje cells in a mouse model of MS, chronic relapsing experimental allergic encephalomyelitis. We also demonstrate SNS mRNA and protein expression within Purkinje cells from tissue obtained postmortem from patients with MS, but not in control subjects with no neurological disease. These results demonstrate a change in sodium channel expression in neurons within the brain in an animal model of MS and in humans with MS and suggest that abnormal patterns of neuronal ion channel expression may contribute to clinical abnormalities such as ataxia in these disorders.

  17. Abnormal Subcortical Brain Morphology in Patients with Knee Osteoarthritis: A Cross-sectional Study

    PubMed Central

    Mao, Cui Ping; Bai, Zhi Lan; Zhang, Xiao Na; Zhang, Qiu Juan; Zhang, Lei

    2016-01-01

    Despite the involvement of subcortical brain structures in the pathogenesis of chronic pain and persistent pain as the defining symptom of knee osteoarthritis (KOA), little attention has been paid to the morphometric measurements of these subcortical nuclei in patients with KOA. The purpose of this study is to explore the potential morphological abnormalities of subcortical brain structures in patients with KOA as compared to the healthy control subjects by using high-resolution MRI. Structural MR data were acquired from 26 patients with KOA and 31 demographically similar healthy individuals. The MR data were analyzed by using FMRIB’s integrated registration and segmentation tool. Both volumetric analysis and surface-based shape analysis were performed to characterize the subcortical morphology. The normalized volumes of bilateral caudate nucleus were significantly smaller in the KOA group than in the control group (P = 0.004). There was also a trend toward smaller volume of the hippocampus in KOA as compared to the control group (P = 0.027). Detailed surface analyses further localized these differences with a greater involvement of the left hemisphere (P < 0.05, corrected) for the caudate nucleus. Hemispheric asymmetry (right larger than left) of the caudate nucleus was found in both KOA and control groups. Besides, no significant correlation was found between the structural data and pain intensities. Our results indicated that patients with KOA had statistically significant smaller normalized volumes of bilateral caudate nucleus and a trend toward smaller volume of the hippocampus as compared to the control subjects. Further investigations are necessary to characterize the role of caudate nucleus in the course of chronicity of pain associated with KOA. PMID:26834629

  18. Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

    2015-03-01

    Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

  19. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium.

    PubMed

    van Erp, T G M; Hibar, D P; Rasmussen, J M; Glahn, D C; Pearlson, G D; Andreassen, O A; Agartz, I; Westlye, L T; Haukvik, U K; Dale, A M; Melle, I; Hartberg, C B; Gruber, O; Kraemer, B; Zilles, D; Donohoe, G; Kelly, S; McDonald, C; Morris, D W; Cannon, D M; Corvin, A; Machielsen, M W J; Koenders, L; de Haan, L; Veltman, D J; Satterthwaite, T D; Wolf, D H; Gur, R C; Gur, R E; Potkin, S G; Mathalon, D H; Mueller, B A; Preda, A; Macciardi, F; Ehrlich, S; Walton, E; Hass, J; Calhoun, V D; Bockholt, H J; Sponheim, S R; Shoemaker, J M; van Haren, N E M; Hulshoff Pol, H E; Pol, H E H; Ophoff, R A; Kahn, R S; Roiz-Santiañez, R; Crespo-Facorro, B; Wang, L; Alpert, K I; Jönsson, E G; Dimitrova, R; Bois, C; Whalley, H C; McIntosh, A M; Lawrie, S M; Hashimoto, R; Thompson, P M; Turner, J A

    2016-04-01

    The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness. PMID:26033243

  20. Abnormal brain function of the rat neonate in a prenatal 5-bromo-2'-deoxyuridine (BrdU)-induced developmental disorder model.

    PubMed

    Ogawa, Tetsuo; Kuwagata, Makiko; Muneoka, Katsumasa; Wakai, Chizu; Senuma, Mika; Kubo, Hiroko; Shioda, Seiji

    2012-10-01

    Neonatal brain function was investigated in a prenatal BrdU-induced developmental disorder model, which has been reported to exhibit behavioral abnormalities such as locomotor hyperactivity, impaired learning and memory, and lower anxiety in offspring. After 1h home cage deprivation we observed an increase in the number of c-Fos (neuronal activity marker) immunoreactive cells in several brain regions of the olfactory and stress-related areas in normal neonates at 11 days. Next, pregnant rats were exposed to 50mg/kg of BrdU from gestation days 9-15, and their offspring at 11 days were home-cage deprived. Compared to vehicle control, the number of c-Fos immunoreactive cells in BrdU group was found to be decreased in the piriform cortex and locus coeruleus, which are known to play an important role in neonatal learning and memory. We also analyzed Pearson product-moment correlation coefficient of the number of c-Fos immunoreactive cells, focusing on the piriform cortex and locus coeruleus versus numerous other brain areas (11 areas including amygdala). Numerous significant correlations were observed in the vehicle control group, however, correlations of the locus coeruleus disappeared in the BrdU group. By observing c-Fos immunoreactivity after home cage deprivation our study uncovers abnormal brain functions as early as postnatal day 11 in this disorder model. Based on these results, we propose a new histological approach for functional characterization of developmental disorder models. PMID:22609825

  1. Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS)

    PubMed Central

    2011-01-01

    Background Bardet-Biedl syndrome (BBS) is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems. Methods A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures. Results All 21 patients with BBS were found to have statistically significant region- and tissue-specific patterns of brain abnormalities. There was 1) normal intracranial volume; 2) reduced white matter in all regions of the brain, but most in the occipital region; 3) preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4) reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5) increased cerebrospinal fluid volume. Conclusions There are distinct and characteristic abnormalities in tissue- and region- specific volumes of the brain in patients

  2. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    PubMed Central

    Hermes, Gretchen; Ajioka, James W; Kelly, Krystyna A; Mui, Ernest; Roberts, Fiona; Kasza, Kristen; Mayr, Thomas; Kirisits, Michael J; Wollmann, Robert; Ferguson, David JP; Roberts, Craig W; Hwang, Jong-Hee; Trendler, Toria; Kennan, Richard P; Suzuki, Yasuhiro; Reardon, Catherine; Hickey, William F; Chen, Lieping; McLeod, Rima

    2008-01-01

    , CD4+ and CD8+ T cells, and activated microglia in perivascular areas and brain parenchyma. Genetically resistant, chronically infected mice had substantially less inflammation. Conclusion In outbred mice, chronic, adult acquired T. gondii infection causes neurologic and behavioral abnormalities secondary to inflammation and loss of brain parenchyma. Perivascular inflammation is prominent particularly contiguous to the aqueduct of Sylvius and hippocampus. Even resistant mice have perivascular inflammation. This mouse model of chronic T. gondii infection raises questions of whether persistence of this parasite in brain can cause inflammation or neurodegeneration in genetically susceptible hosts. PMID:18947414

  3. Abnormal Brain Dynamics Underlie Speech Production in Children with Autism Spectrum Disorder.

    PubMed

    Pang, Elizabeth W; Valica, Tatiana; MacDonald, Matt J; Taylor, Margot J; Brian, Jessica; Lerch, Jason P; Anagnostou, Evdokia

    2016-02-01

    A large proportion of children with autism spectrum disorder (ASD) have speech and/or language difficulties. While a number of structural and functional neuroimaging methods have been used to explore the brain differences in ASD with regards to speech and language comprehension and production, the neurobiology of basic speech function in ASD has not been examined. Magnetoencephalography (MEG) is a neuroimaging modality with high spatial and temporal resolution that can be applied to the examination of brain dynamics underlying speech as it can capture the fast responses fundamental to this function. We acquired MEG from 21 children with high-functioning autism (mean age: 11.43 years) and 21 age- and sex-matched controls as they performed a simple oromotor task, a phoneme production task and a phonemic sequencing task. Results showed significant differences in activation magnitude and peak latencies in primary motor cortex (Brodmann Area 4), motor planning areas (BA 6), temporal sequencing and sensorimotor integration areas (BA 22/13) and executive control areas (BA 9). Our findings of significant functional brain differences between these two groups on these simple oromotor and phonemic tasks suggest that these deficits may be foundational and could underlie the language deficits seen in ASD. PMID:26363154

  4. Brain metabolite abnormalities in ventromedial prefrontal cortex are related to duration of hypercortisolism and anxiety in patients with Cushing's syndrome.

    PubMed

    Crespo, Iris; Santos, Alicia; Gómez-Ansón, Beatriz; López-Mourelo, Olga; Pires, Patricia; Vives-Gilabert, Yolanda; Webb, Susan M; Resmini, Eugenia

    2016-09-01

    Chronic exposure to excessive glucocorticoid (GC) concentration in Cushing's syndrome (CS) can affect the brain structurally and functionally; ventromedial prefrontal cortex (vmPFC) is rich in GC receptors and therefore particularly vulnerable to excessive GC concentration. Proton magnetic resonance spectroscopy ((1)H-MRS) is a sensitive, non-invasive imaging technique that provides information on brain metabolites in vivo. Our aim was to investigate metabolite concentrations in vmPFC of CS patients and their relationship with clinical outcome. Twenty-two right-handed CS patients (7 active/15 in remission, 19 females, 41.6 ± 12.3 years) and 22 right-handed healthy controls (14 females, 41.7 ± 11 years) underwent brain MRI and (1)H-MRS exams at 3 Tesla. Concentrations of glutamate (Glu), glutamate + glutamine (Glx), creatine (Cr), N-Acetyl-aspartate (NAA), N-Acetyl-aspartate + N-acetylaspartylglutamate (total NAA), choline-containing compounds (Cho) and myoinositol (MI) were determined. Moreover, anxiety and depressive symptoms were evaluated with the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory-II (BDI-II) test, respectively. CS patients had lower concentrations of glutamate and total NAA in the vmPFC than healthy controls (8.6 ± 1.2 vs. 9.3 ± 0.7 mmol/L, and 6.4 ± 0.8 vs. 6.8 ± 0.4 mmol/L, respectively; p < 0.05). Duration of hypercortisolism was negatively correlated with total NAA (r = -0.488, p < 0.05). Moreover, the concentration of total NAA was negatively correlated with anxiety state (r = -0.359, p < 0.05). Brain metabolites are abnormal in the vmPFC of patients with CS. Decreased total NAA and glutamate concentrations indicate neuronal dysfunction that appear to be related with duration of hypercortisolism and anxiety. PMID:27103571

  5. The restless brain: how intrinsic activity organizes brain function

    PubMed Central

    Raichle, Marcus E.

    2015-01-01

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869

  6. The restless brain: how intrinsic activity organizes brain function.

    PubMed

    Raichle, Marcus E

    2015-05-19

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869

  7. Abnormal fusiform activation during emotional-face encoding assessed with functional magnetic resonance imaging.

    PubMed

    Adleman, Nancy E; Kayser, Reilly R; Olsavsky, Aviva K; Bones, Brian L; Muhrer, Eli J; Fromm, Stephen J; Pine, Daniel S; Zarate, Carlos; Leibenluft, Ellen; Brotman, Melissa A

    2013-05-30

    This functional magnetic resonance imaging study shows that children and adults with bipolar disorder (BD), compared with healthy subjects, exhibit impaired memory for emotional faces and abnormal fusiform activation during encoding. Fusiform activation abnormalities in BD were correlated with mania severity and may therefore represent a trait and state BD biomarker. PMID:23541333

  8. Abnormal fusiform activation during emotional-face encoding in children and adults with bipolar disorder

    PubMed Central

    Adleman, Nancy E.; Kayser, Reilly R.; Olsavsky, Aviva K.; Bones, Brian L.; Muhrer, Eli J.; Fromm, Stephen J.; Pine, Daniel S.; Zarate, Carlos; Leibenluft, Ellen; Brotman, Melissa A.

    2013-01-01

    This fMRI study shows that, compared to healthy subjects, children and adults with bipolar disorder (BD) exhibit impaired memory for emotional faces and abnormal fusiform activation during encoding. Fusiform activation abnormalities in BD were correlated with mania severity and may therefore represent a trait and state BD biomarker. PMID:23541333

  9. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  10. Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection.

    PubMed

    Fennema-Notestine, Christine; Ellis, Ronald J; Archibald, Sarah L; Jernigan, Terry L; Letendre, Scott L; Notestine, Randy J; Taylor, Michael J; Theilmann, Rebecca J; Julaton, Michelle D; Croteau, David J; Wolfson, Tanya; Heaton, Robert K; Gamst, Anthony C; Franklin, Donald R; Clifford, David B; Collier, Ann C; Gelman, Benjamin B; Marra, Christina; McArthur, Justin C; McCutchan, J Allen; Morgello, Susan; Simpson, David M; Grant, Igor

    2013-08-01

    MRI alterations in the cerebral white (WM) and gray matter (GM) are common in HIV infection, even during successful combination antiretroviral therapy (CART), and their pathophysiology and clinical significance are unclear. We evaluated the association of these alterations with recovery of CD4+ T cells. Seventy-five HIV-infected (HIV+) volunteers in the CNS HIV Anti-Retroviral Therapy Effects Research study underwent brain MRI at two visits. Multi-channel morphometry yielded volumes of total cerebral WM, abnormal WM, cortical and subcortical GM, and ventricular and sulcal CSF. Multivariable linear regressions were used to predict volumetric changes with change in current CD4 and detectable HIV RNA. On average, the cohort (79 % initially on CART) demonstrated loss of total cerebral WM alongside increases in abnormal WM and ventricular volumes. A greater extent of CD4 recovery was associated with increases in abnormal WM and subcortical GM volumes. Virologic suppression was associated with increased subcortical GM volume, independent of CD4 recovery. These findings suggest a possible link between brain alterations and immune recovery, distinct from the influence of virologic suppression. The association of increasing abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggests that neuroinflammation may be one mechanism in CNS pathogenesis. PMID:23838849

  11. Conditional Tat protein brain expression in the GT-tg bigenic mouse induces cerebral fractional anisotropy abnormalities

    PubMed Central

    Carey, Amanda N.; Liu, Xiaoxu; Mintzopoulos, Dionyssios; Paris, Jason J.; McLaughlin, Jay P.; Kaufman, Marc J.

    2015-01-01

    Cerebral white matter changes including tissue water diffusion abnormalities detected with diffusion tensor magnetic resonance imaging (DTI) are commonly found in humans with Human Immunodeficiency Virus (HIV) infection, as well as in animal models of the disorder. The severities of some of these abnormalities have been reported to correlate with measures of disease progression or severity, or with the degree of cognitive dysfunction. Accordingly, DTI may be a useful translational biomarker. HIV-Tat protein appears to be an important factor in the viral pathogenesis of HIV-associated neurotoxicity. We previously reported cerebral gray matter density reductions in the GT-tg bigenic mouse treated with doxycycline (Dox) to conditionally induce Tat protein expression. Presently, we administered intraperitoneal (i.p.) Dox (100 mg/kg/day) for 7 days to GT-tg mice to determine whether induction of conditional Tat expression led to the development of cerebral DTI abnormalities. Perfused and fixed brains from eight GT-tg mice administered Dox and eight control mice administered saline i.p. were extracted and underwent DTI scans on a 9.4 Tesla scanner. A whole brain analysis detected fractional anisotropy (FA) reductions in several areas including insular and endopiriform regions, as well as within the dorsal striatum. These findings suggest that exposure to Tat protein is sufficient to induce FA abnormalities, and further support the use of the GT-tg mouse to model some effects of HIV. PMID:25619988

  12. [Brain, psyche and physical activity].

    PubMed

    Hollmann, W; Strüder, H K

    2000-11-01

    Modern technical and biochemical methods allow investigation of hemodynamic and metabolic responses of the human brain during muscular work. Following a general introduction to the topic results from selected studies on endogenous opioid peptides, pain sensitivity and psyche, regional cerebral blood flow and cerebral glucose metabolism, amino acid transport across the blood-brain barrier, impact of physical work on the serotonergic system, influence of oxygen partial pressure on neurotransmitters and hormones during exercise, role of the brain as performance limiting factor as well as age-related changes in cerebral blood flow and hypothalamo-pituitary-adrenal/-gonadal axis function will be presented. PMID:11149280

  13. Active tactile exploration using a brain-machine-brain interface.

    PubMed

    O'Doherty, Joseph E; Lebedev, Mikhail A; Ifft, Peter J; Zhuang, Katie Z; Shokur, Solaiman; Bleuler, Hannes; Nicolelis, Miguel A L

    2011-11-10

    Brain-machine interfaces use neuronal activity recorded from the brain to establish direct communication with external actuators, such as prosthetic arms. It is hoped that brain-machine interfaces can be used to restore the normal sensorimotor functions of the limbs, but so far they have lacked tactile sensation. Here we report the operation of a brain-machine-brain interface (BMBI) that both controls the exploratory reaching movements of an actuator and allows signalling of artificial tactile feedback through intracortical microstimulation (ICMS) of the primary somatosensory cortex. Monkeys performed an active exploration task in which an actuator (a computer cursor or a virtual-reality arm) was moved using a BMBI that derived motor commands from neuronal ensemble activity recorded in the primary motor cortex. ICMS feedback occurred whenever the actuator touched virtual objects. Temporal patterns of ICMS encoded the artificial tactile properties of each object. Neuronal recordings and ICMS epochs were temporally multiplexed to avoid interference. Two monkeys operated this BMBI to search for and distinguish one of three visually identical objects, using the virtual-reality arm to identify the unique artificial texture associated with each. These results suggest that clinical motor neuroprostheses might benefit from the addition of ICMS feedback to generate artificial somatic perceptions associated with mechanical, robotic or even virtual prostheses. PMID:21976021

  14. Alteration of spontaneous brain activity in COPD patients

    PubMed Central

    Zhang, Jiaxing; Chen, Ji; Yu, Qian; Fan, Cunxiu; Zhang, Ran; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2016-01-01

    Background and objective Airflow limitation in chronic obstructive pulmonary disease (COPD) results in a decrease in oxygen transport to the brain. The aim of the present study was to explore the alteration of spontaneous brain activity induced by hypoxia in patients with COPD. Patients and methods Twenty-five stable patients with COPD and 25 matching healthy volunteers were investigated. Amplitude of low-frequency fluctuation (ALFF) of blood oxygenation level-dependent signal at resting state in the brain was analyzed using functional magnetic resonance imaging. Results Whole-brain analysis using functional magnetic resonance imaging revealed significant decreases in ALFF in the bilateral posterior cingulate gyri and right lingual gyrus and an increase in ALFF in the left postcentral gyrus of patients with COPD. After controlling for SaO2, patients with COPD only showed an increase in ALFF in the left postcentral gyrus. Region of interest analysis showed a decrease in ALFF in the left precentral gyrus and an increase in ALFF in the left caudate nucleus of patients with COPD. In all subjects, ALFF in the bilateral posterior cingulate gyri and right lingual gyrus showed positive correlations with visual reproduction. Conclusion We demonstrated abnormal spontaneous brain activity of patients with COPD, which may have a pathophysiologic meaning. PMID:27555761

  15. Recording of brain activity across spatial scales.

    PubMed

    Lewis, C M; Bosman, C A; Fries, P

    2015-06-01

    Brain activity reveals exquisite coordination across spatial scales, from local microcircuits to brain-wide networks. Understanding how the brain represents, transforms and communicates information requires simultaneous recordings from distributed nodes of whole brain networks with single-cell resolution. Realizing multi-site recordings from communicating populations is hampered by the need to isolate clusters of interacting cells, often on a day-to-day basis. Chronic implantation of multi-electrode arrays allows long-term tracking of activity. Lithography on thin films provides a means to produce arrays of variable resolution, a high degree of flexibility, and minimal tissue displacement. Sequential application of surface arrays to monitor activity across brain-wide networks and subsequent implantation of laminar arrays to target specific populations enables continual refinement of spatial scale while maintaining coverage. PMID:25544724

  16. Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice.

    PubMed

    Li, Qi; Chan, Siu Yuen; Wong, Kwun K; Wei, Ran; Leung, Yu On; Ding, Abby Y; Hui, Tomy C K; Cheung, Charlton; Chua, Siew E; Sham, Pak C; Wu, Ed X; McAlonan, Grainne M

    2016-07-01

    Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more 'sensitive' to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits. PMID:26826030

  17. Deficiency of the chromatin regulator BRPF1 causes abnormal brain development.

    PubMed

    You, Linya; Zou, Jinfeng; Zhao, Hong; Bertos, Nicholas R; Park, Morag; Wang, Edwin; Yang, Xiang-Jiao

    2015-03-13

    Epigenetic mechanisms are important in different neurological disorders, and one such mechanism is histone acetylation. The multivalent chromatin regulator BRPF1 (bromodomain- and plant homeodomain-linked (PHD) zinc finger-containing protein 1) recognizes different epigenetic marks and activates three histone acetyltransferases, so it is both a reader and a co-writer of the epigenetic language. The three histone acetyltransferases are MOZ, MORF, and HBO1, which are also known as lysine acetyltransferase 6A (KAT6A), KAT6B, and KAT7, respectively. The MORF gene is mutated in four neurodevelopmental disorders sharing the characteristic of intellectual disability and frequently displaying callosal agenesis. Here, we report that forebrain-specific inactivation of the mouse Brpf1 gene caused early postnatal lethality, neocortical abnormalities, and partial callosal agenesis. With respect to the control, the mutant forebrain contained fewer Tbr2-positive intermediate neuronal progenitors and displayed aberrant neurogenesis. Molecularly, Brpf1 loss led to decreased transcription of multiple genes, such as Robo3 and Otx1, important for neocortical development. Surprisingly, elevated expression of different Hox genes and various other transcription factors, such as Lhx4, Foxa1, Tbx5, and Twist1, was also observed. These results thus identify an important role of Brpf1 in regulating forebrain development and suggest that it acts as both an activator and a silencer of gene expression in vivo. PMID:25568313

  18. Deficiency of the Chromatin Regulator Brpf1 Causes Abnormal Brain Development*

    PubMed Central

    You, Linya; Zou, Jinfeng; Zhao, Hong; Bertos, Nicholas R.; Park, Morag; Wang, Edwin; Yang, Xiang-Jiao

    2015-01-01

    Epigenetic mechanisms are important in different neurological disorders, and one such mechanism is histone acetylation. The multivalent chromatin regulator BRPF1 (bromodomain- and plant homeodomain-linked (PHD) zinc finger-containing protein 1) recognizes different epigenetic marks and activates three histone acetyltransferases, so it is both a reader and a co-writer of the epigenetic language. The three histone acetyltransferases are MOZ, MORF, and HBO1, which are also known as lysine acetyltransferase 6A (KAT6A), KAT6B, and KAT7, respectively. The MORF gene is mutated in four neurodevelopmental disorders sharing the characteristic of intellectual disability and frequently displaying callosal agenesis. Here, we report that forebrain-specific inactivation of the mouse Brpf1 gene caused early postnatal lethality, neocortical abnormalities, and partial callosal agenesis. With respect to the control, the mutant forebrain contained fewer Tbr2-positive intermediate neuronal progenitors and displayed aberrant neurogenesis. Molecularly, Brpf1 loss led to decreased transcription of multiple genes, such as Robo3 and Otx1, important for neocortical development. Surprisingly, elevated expression of different Hox genes and various other transcription factors, such as Lhx4, Foxa1, Tbx5, and Twist1, was also observed. These results thus identify an important role of Brpf1 in regulating forebrain development and suggest that it acts as both an activator and a silencer of gene expression in vivo. PMID:25568313

  19. Understanding the brain by controlling neural activity

    PubMed Central

    Krug, Kristine; Salzman, C. Daniel; Waddell, Scott

    2015-01-01

    Causal methods to interrogate brain function have been employed since the advent of modern neuroscience in the nineteenth century. Initially, randomly placed electrodes and stimulation of parts of the living brain were used to localize specific functions to these areas. Recent technical developments have rejuvenated this approach by providing more precise tools to dissect the neural circuits underlying behaviour, perception and cognition. Carefully controlled behavioural experiments have been combined with electrical devices, targeted genetically encoded tools and neurochemical approaches to manipulate information processing in the brain. The ability to control brain activity in these ways not only deepens our understanding of brain function but also provides new avenues for clinical intervention, particularly in conditions where brain processing has gone awry. PMID:26240417

  20. Persistent frontal P300 brain potential suggests abnormal processing of auditory information in distractible children.

    PubMed

    Kilpeläinen, R; Luoma, L; Herrgård, E; Yppärilä, H; Partanen, J; Karhu, J

    1999-11-01

    The P300 event-related potential (ERP) was studied at the beginning, in the middle, and at the end of an auditory stimulus discrimination task in 70 normal 9-year-old children. Easily distractible children showed frontally a short-latency P300 response to target stimuli throughout the task, whereas in the non-distractible children the corresponding response was distinctly smaller and also showed a tendency to decrease in size towards the end of the task. The short-latency frontal P300 response reflects activation of the brain's orienting networks, and it normally decreases in size when stimuli lose their 'novelty value' with stimulus repetition. Persistent frontal P300 suggest that distractible children continued to show enhanced orienting to stimuli that should have already been well encoded and/or categorized. PMID:10599853

  1. Annual Research Review: Growth connectomics – the organization and reorganization of brain networks during normal and abnormal development

    PubMed Central

    Vértes, Petra E; Bullmore, Edward T

    2015-01-01

    Background We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). Synthesis We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. Conclusions We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. PMID:25441756

  2. Circulating Omega‐3 Polyunsaturated Fatty Acids and Subclinical Brain Abnormalities on MRI in Older Adults: The Cardiovascular Health Study

    PubMed Central

    Virtanen, Jyrki K.; Siscovick, David S.; Lemaitre, Rozenn N.; Longstreth, William T.; Spiegelman, Donna; Rimm, Eric B.; King, Irena B.; Mozaffarian, Dariush

    2013-01-01

    Background Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega‐3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI. Methods and Results In the community‐based Cardiovascular Health Study, 3660 participants aged ≥65 underwent brain MRI in 1992–1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992–1993 and related to cross‐sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest long‐chain omega‐3 PUFA quartile. Higher long‐chain omega‐3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate‐chain omega‐3 PUFA alpha‐linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha‐linolenic acid intake. Conclusions Among older adults, higher phospholipid long‐chain omega‐3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long‐chain omega‐3 PUFAs, on brain health in later life. The role of plant‐derived alpha‐linolenic acid in brain health requires further investigation. PMID:24113325

  3. Intrinsic brain activity as a diagnostic biomarker in children with benign epilepsy with centrotemporal spikes.

    PubMed

    Zhu, Yihong; Yu, Yang; Shinkareva, Svetlana V; Ji, Gong-Jun; Wang, Jue; Wang, Zhong-Jin; Zang, Yu-Feng; Liao, Wei; Tang, Ye-Lei

    2015-10-01

    Benign epilepsy with centrotemporal spikes (BECTS) is often associated with neural circuit dysfunction, particularly during the transient active state characterized by interictal epileptiform discharges (IEDs). Little is known, however, about the functional neural circuit abnormalities in BECTS without IEDs, or if such abnormalities could be used to differentiate BECTS patients without IEDs from healthy controls (HCs) for early diagnosis. To this end, we conducted resting-state functional magnetic resonance imaging (RS-fMRI) and simultaneous Electroencephalogram (EEG) in children with BECTS (n = 43) and age-matched HC (n = 28). The simultaneous EEG recordings distinguished BECTS with IEDs (n = 20) from without IEDs (n = 23). Intrinsic brain activity was measured in all three groups using the amplitude of low frequency fluctuation at rest. Compared to HC, BECTS patients with IEDs exhibited an intrinsic activity abnormality in the thalamus, suggesting that thalamic dysfunction could contribute to IED emergence while patients without IEDs exhibited intrinsic activity abnormalities in middle frontal gyrus and superior parietal gyrus. Using multivariate pattern classification analysis, we were able to differentiate BECTS without IEDs from HCs with 88.23% accuracy. BECTS without epileptic transients can be distinguished from HC and BECTS with IEDs by unique regional abnormalities in resting brain activity. Both transient abnormalities as reflected by IEDs and chronic abnormalities as reflected by RS-fMRI may contribute to BECTS development and expression. Intrinsic brain activity and multivariate pattern classification techniques are promising tools to diagnose and differentiate BECTS syndromes. Hum Brain Mapp 36:3878-3889, 2015. © 2015 Wiley Periodicals, Inc. PMID:26173095

  4. Novel Molecular Pathways Elicited by Mutant FGFR2 May Account for Brain Abnormalities in Apert Syndrome

    PubMed Central

    Yeh, Erika; Fanganiello, Roberto D.; Sunaga, Daniele Y.; Zhou, Xueyan; Holmes, Gregory; Rocha, Katia M.; Alonso, Nivaldo; Matushita, Hamilton; Wang, Yingli; Jabs, Ethylin W.; Passos-Bueno, Maria Rita

    2013-01-01

    Apert syndrome (AS), the most severe form craniosynostosis, is characterized by premature fusion of coronal sutures. Approximately 70% of AS patients carry S252W gain-of-function mutation in FGFR2. Besides the cranial phenotype, brain dysmorphologies are present and are not seen in other FGFR2-asociated craniosynostosis, such as Crouzon syndrome (CS). Here, we hypothesized that S252W mutation leads not only to overstimulation of FGFR2 downstream pathway, but likewise induces novel pathological signaling. First, we profiled global gene expression of wild-type and S252W periosteal fibroblasts stimulated with FGF2 to activate FGFR2. The great majority (92%) of the differentially expressed genes (DEGs) were divergent between each group of cell populations and they were regulated by different transcription factors. We than compared gene expression profiles between AS and CS cell populations and did not observe correlations. Therefore, we show for the first time that S252W mutation in FGFR2 causes a unique cell response to FGF2 stimulation. Since our gene expression results suggested that novel signaling elicited by mutant FGFR2 might be associated with central nervous system (CNS) development and maintenance, we next investigated if DEGs found in AS cells were also altered in the CNS of an AS mouse model. Strikingly, we validated Strc (stereocilin) in newborn Fgfr2S252W/+ mouse brain. Moreover, immunostaining experiments suggest a role for endothelial cells and cerebral vasculature in the establishment of characteristic CNS dysmorphologies in AS that has not been proposed by previous literature. Our approach thus led to the identification of new target genes directly or indirectly associated with FGFR2 which are contributing to the pathophysiology of AS. PMID:23593218

  5. An Abnormal Nitric Oxide Metabolism Contributes to Brain Oxidative Stress in the Mouse Model for the Fragile X Syndrome, a Possible Role in Intellectual Disability

    PubMed Central

    Lima-Cabello, Elena; Garcia-Guirado, Francisco; Calvo-Medina, Rocio; el Bekay, Rajaa; Perez-Costillas, Lucia; Quintero-Navarro, Carolina; Sanchez-Salido, Lourdes

    2016-01-01

    Background. Fragile X syndrome is the most common genetic cause of mental disability. Although many research has been performed, the mechanism underlying the pathogenesis is unclear and needs further investigation. Oxidative stress played major roles in the syndrome. The aim was to investigate the nitric oxide metabolism, protein nitration level, the expression of NOS isoforms, and furthermore the activation of the nuclear factor NF-κB-p65 subunit in different brain areas on the fragile X mouse model. Methods. This study involved adult male Fmr1-knockout and wild-type mice as controls. We detected nitric oxide metabolism and the activation of the nuclear factor NF-κBp65 subunit, comparing the mRNA expression and protein content of the three NOS isoforms in different brain areas. Results. Fmr1-KO mice showed an abnormal nitric oxide metabolism and increased levels of protein tyrosine nitrosylation. Besides that, nuclear factor NF-κB-p65 and inducible nitric oxide synthase appeared significantly increased in the Fmr1-knockout mice. mRNA and protein levels of the neuronal nitric oxide synthase appeared significantly decreased in the knockout mice. However, the epithelial nitric oxide synthase isoform displayed no significant changes. Conclusions. These data suggest the potential involvement of an abnormal nitric oxide metabolism in the pathogenesis of the fragile X syndrome. PMID:26788253

  6. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

    PubMed Central

    Huang, Ming-Xiong; Nichols, Sharon; Baker, Dewleen G.; Robb, Ashley; Angeles, Annemarie; Yurgil, Kate A.; Drake, Angela; Levy, Michael; Song, Tao; McLay, Robert; Theilmann, Rebecca J.; Diwakar, Mithun; Risbrough, Victoria B.; Ji, Zhengwei; Huang, Charles W.; Chang, Douglas G.; Harrington, Deborah L.; Muzzatti, Laura; Canive, Jose M.; Christopher Edgar, J.; Chen, Yu-Han; Lee, Roland R.

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1–4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1–4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI. PMID:25009772

  7. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury.

    PubMed

    Huang, Ming-Xiong; Nichols, Sharon; Baker, Dewleen G; Robb, Ashley; Angeles, Annemarie; Yurgil, Kate A; Drake, Angela; Levy, Michael; Song, Tao; McLay, Robert; Theilmann, Rebecca J; Diwakar, Mithun; Risbrough, Victoria B; Ji, Zhengwei; Huang, Charles W; Chang, Douglas G; Harrington, Deborah L; Muzzatti, Laura; Canive, Jose M; Christopher Edgar, J; Chen, Yu-Han; Lee, Roland R

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1-4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1-4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI. PMID:25009772

  8. Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms.

    PubMed

    Bearden, Carrie E; van Erp, Theo G M; Monterosso, John R; Simon, Tony J; Glahn, David C; Saleh, Peter A; Hill, Nicole M; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Cannon, Tyrone D

    2004-06-01

    Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships. PMID:15788257

  9. An a contrario approach for the detection of patient-specific brain perfusion abnormalities with arterial spin labelling.

    PubMed

    Maumet, Camille; Maurel, Pierre; Ferré, Jean-Christophe; Barillot, Christian

    2016-07-01

    In this paper, we introduce a new locally multivariate procedure to quantitatively extract voxel-wise patterns of abnormal perfusion in individual patients. This a contrario approach uses a multivariate metric from the computer vision community that is suitable to detect abnormalities even in the presence of closeby hypo- and hyper-perfusions. This method takes into account local information without applying Gaussian smoothing to the data. Furthermore, to improve on the standard a contrario approach, which assumes white noise, we introduce an updated a contrario approach that takes into account the spatial coherency of the noise in the probability estimation. Validation is undertaken on a dataset of 25 patients diagnosed with brain tumours and 61 healthy volunteers. We show how the a contrario approach outperforms the massively univariate general linear model usually employed for this type of analysis. PMID:27039702

  10. Whole-brain activity mapping onto a zebrafish brain atlas.

    PubMed

    Randlett, Owen; Wee, Caroline L; Naumann, Eva A; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E; Portugues, Ruben; Lacoste, Alix M B; Riegler, Clemens; Engert, Florian; Schier, Alexander F

    2015-11-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal–regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors. PMID:26778924

  11. Whole-brain activity mapping onto a zebrafish brain atlas

    PubMed Central

    Randlett, Owen; Wee, Caroline L.; Naumann, Eva A.; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E.; Portugues, Ruben; Lacoste, Alix M.B.; Riegler, Clemens; Engert, Florian; Schier, Alexander F.

    2015-01-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open source atlas containing molecular labels and anatomical region definitions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated-Extracellular signal-regulated kinase (ERK/MAPK) as a readout of neural activity, we have developed a system to create and contextualize whole brain maps of stimulus- and behavior-dependent neural activity. This MAP-Mapping (Mitogen Activated Protein kinase – Mapping) assay is technically simple, fast, inexpensive, and data analysis is completely automated. Since MAP-Mapping is performed on fish that are freely swimming, it is applicable to nearly any stimulus or behavior. We demonstrate the utility of our high-throughput approach using hunting/feeding, pharmacological, visual and noxious stimuli. The resultant maps outline hundreds of areas associated with behaviors. PMID:26778924

  12. Cardiac repolarization abnormalities and increased sympathetic activity in scleroderma.

    PubMed Central

    Ciftci, Orcun; Onat, Ahmet Mesut; Yavuz, Bunyamin; Akdogan, Ali; Aytemir, Kudret; Tokgozoglu, Lale; Sahiner, Levent; Deniz, Ali; Ureten, Kemal; Kizilca, Guler; Calguneri, Meral; Oto, Ali

    2007-01-01

    BACKGROUND: Cardiac involvement in scleroderma is a poor prognostic sign and is usually underdiagnosed, particularly in asymptomatic patient. This paper focuses on QT dynamicity and heart rate variability (HRV) in patients with scleroderma and controls in an attempt to investigate the cardiac autonomic system and ventricular repolarization. METHODS: Sixty patients with scleroderma and 30 age- and sex-matched healthy controls who had no cardiovascular risk factors were included in this study. All patients and the controls underwent a 24-hour holter recording as well as a transthoracic echocardiography. HRV and QT dynamicity parameters were calculated. RESULTS: In HRV analysis, autonomic balance was changed in favor of the sympathetic system in patients with diffuse scleroderma. In QT dynamicity analysis, QT/RR slopes were significantly steeper in patients with diffuse scleroderma compared to patients with limited scleroderma and controls (QTapex/RR: 0.24 +/- 0.16, 0.15 +/- 0.03, 0.14 +/- 0.03 respectively p < 0.001; QTend/RR: 0.26 +/- 0.17, 0.14 +/- 0.04, 0.13 +/- 0.05, respectively p < 0.001). CONCLUSIONS: Patients with diffuse scleroderma may have asymptomatic cardiac repolarization abnormalities and autonomic dysfunction. Our results may indicate that QT dynamicity and HRV can be useful noninvasive methods that may detect impaired state of autonomic balance and cardiac repolarization in patients with diffuse scleroderma. PMID:17393947

  13. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    USGS Publications Warehouse

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

  14. Red-Backed Vole Brain Promotes Highly Efficient In Vitro Amplification of Abnormal Prion Protein from Macaque and Human Brains Infected with Variant Creutzfeldt-Jakob Disease Agent

    PubMed Central

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in vCJD-infected human

  15. Cortico-striato-thalamo-cortical circuit abnormalities in obsessive-compulsive disorder: A voxel-based morphometric and fMRI study of the whole brain.

    PubMed

    Tang, Wenxin; Zhu, Qifeng; Gong, Xiangyang; Zhu, Cheng; Wang, Yiquan; Chen, Shulin

    2016-10-15

    The primary aim of this study was to identify structural and functional abnormalities in the brains of obsessive-compulsive disorder (OCD) patients. Another aim was to assess the effect of serotonin selective reuptake inhibitors (SSRIs) on brain structure of OCD patients. All subjects underwent brain magnetic resonance imaging (MRI) and resting functional MRI (fMRI). High-resolution three-dimensional images were processed using the voxel-based morphometry (VBM) method. The final analysis included 18 OCD patients and 16 healthy controls. In the OCD patients there was a decrease in gray matter volume in the bilateral cingulate cortex and bilateral striatum. In some cortical structures including the cerebellar anterior lobe, left orbital frontal gyrus, right middle frontal gyrus, left middle temporal gyrus, precentral gyrus, and postcentral gyrus, there was an increase in gray matter volume. On fMRI the OCD patients had overactivation of the right cerebellum and right parietal lobe and reduced activation of the left cingulate gyrus, putamen, and caudate nucleus. Eleven OCD patients who improved during 12 weeks of drug treatment with sertraline hydrochloride had a significant increase in gray matter volume in several brain structures but no significant differences were found on resting fMRI. The results indicated a consistent trend between structural and functional images. Higher cortical structures showed increased gray matter volume and increased activation as did the cerebellum whereas subcortical structures showed decreased gray matter volume and decreased activation. And brain structure improvement consisted with symptom improvement after SSRIs treatment in OCD patients. PMID:27388149

  16. High Incidence of Progressive Postnatal Cerebellar Enlargement in Costello Syndrome: Brain Overgrowth Associated with HRAS Mutations as the Likely Cause of Structural Brain and Spinal Cord Abnormalities

    PubMed Central

    Gripp, Karen W.; Hopkins, Elisabeth; Doyle, Daniel; Dobyns, William B.

    2010-01-01

    Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS. Its presentation includes failure-to-thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. In a systematic review we found absolute or relative macrocephaly (100%), ventriculomegaly (50%), and other abnormalities on brain and spinal cord imaging studies in 27/28 individuals. Posterior fossa crowding with cerebellar tonsillar herniation (CBTH) was noted in 27/28 (96%), and in 10/17 (59%) with serial studies posterior fossa crowding progressed. Sequelae of posterior fossa crowding and CBTH included hydrocephalus requiring shunt or ventriculostomy (25%), Chiari 1 malformation (32%) and syrinx formation (25%). Our data reveal macrocephaly with progressive frontal bossing and CBTH, documenting an ongoing process rather than a static congenital anomaly. Comparison of images obtained in young infants to subsequent studies demonstrated postnatal development of posterior fossa crowding. This process of evolving megalencephaly and cerebellar enlargement is in keeping with mouse model data, delineating abnormal genesis of neurons and glia, resulting in an increased number of astrocytes and enlarged brain volume. In Costello syndrome and macrocephaly-capillary malformation syndrome disproportionate brain growth is the main factor resulting in postnatal CBTH and Chiari 1 malformation. PMID:20425820

  17. Physical activity, brain plasticity, and Alzheimer's disease.

    PubMed

    Erickson, Kirk I; Weinstein, Andrea M; Lopez, Oscar L

    2012-11-01

    In this review we summarize the epidemiological, cross-sectional, and interventional studies examining the association between physical activity and brain volume, function, and risk for Alzheimer's disease. The epidemiological literature provides compelling evidence that greater amounts of physical activity are associated with a reduced risk of dementia in late life. In addition, randomized interventions using neuroimaging tools have reported that participation in physical activity increases the size of prefrontal and hippocampal brain areas, which may lead to a reduction in memory impairments. Consistent with these findings, longitudinal studies using neuroimaging tools also find that the volume of prefrontal and hippocampal brain areas are larger in individuals who engaged in more physical activity earlier in life. We conclude from this review that there is convincing evidence that physical activity has a consistent and robust association with brain regions implicated in age-related cognitive decline and Alzheimer's disease. In addition to summarizing this literature we provide recommendations for future research on physical activity and brain health. PMID:23085449

  18. Abnormal Ventral and Dorsal Attention Network Activity during Single and Dual Target Detection in Schizophrenia

    PubMed Central

    Jimenez, Amy M.; Lee, Junghee; Wynn, Jonathan K.; Cohen, Mark S.; Engel, Stephen A.; Glahn, David C.; Nuechterlein, Keith H.; Reavis, Eric A.; Green, Michael F.

    2016-01-01

    Early visual perception and attention are impaired in schizophrenia, and these deficits can be observed on target detection tasks. These tasks activate distinct ventral and dorsal brain networks which support stimulus-driven and goal-directed attention, respectively. We used single and dual target rapid serial visual presentation (RSVP) tasks during fMRI with an ROI approach to examine regions within these networks associated with target detection and the attentional blink (AB) in 21 schizophrenia outpatients and 25 healthy controls. In both tasks, letters were targets and numbers were distractors. For the dual target task, the second target (T2) was presented at three different lags after the first target (T1) (lag1 = 100 ms, lag3 = 300 ms, lag7 = 700ms). For both single and dual target tasks, patients identified fewer targets than controls. For the dual target task, both groups showed the expected AB effect with poorer performance at lag 3 than at lags 1 or 7, and there was no group by lag interaction. During the single target task, patients showed abnormally increased deactivation of the temporo-parietal junction (TPJ), a key region of the ventral network. When attention demands were increased during the dual target task, patients showed overactivation of the posterior intraparietal cortex, a key dorsal network region, along with failure to deactivate TPJ. Results suggest inefficient and faulty suppression of salience-oriented processing regions, resulting in increased sensitivity to stimuli in general, and difficulty distinguishing targets from non-targets. PMID:27014135

  19. Abnormal Resting State fMRI Activity Predicts Processing Speed Deficits in First-Episode Psychosis

    PubMed Central

    Argyelan, Miklos; Gallego, Juan A; Robinson, Delbert G; Ikuta, Toshikazu; Sarpal, Deepak; John, Majnu; Kingsley, Peter B; Kane, John; Malhotra, Anil K; Szeszko, Philip R

    2015-01-01

    Little is known regarding the neuropsychological significance of resting state functional magnetic resonance imaging (rs-fMRI) activity early in the course of psychosis. Moreover, no studies have used different approaches for analysis of rs-fMRI activity and examined gray matter thickness in the same cohort. In this study, 41 patients experiencing a first-episode of psychosis (including N=17 who were antipsychotic drug-naive at the time of scanning) and 41 individually age- and sex-matched healthy volunteers completed rs-fMRI and structural MRI exams and neuropsychological assessments. We computed correlation matrices for 266 regions-of-interest across the brain to assess global connectivity. In addition, independent component analysis (ICA) was used to assess group differences in the expression of rs-fMRI activity within 20 predefined publicly available templates. Patients demonstrated lower overall rs-fMRI global connectivity compared with healthy volunteers without associated group differences in gray matter thickness assessed within the same regions-of-interest used in this analysis. Similarly, ICA revealed worse rs-fMRI expression scores across all 20 networks in patients compared with healthy volunteers, with posthoc analyses revealing significant (p<0.05; corrected) abnormalities within the caudate nucleus and planum temporale. Worse processing speed correlated significantly with overall lower global connectivity using the region-of-interest approach and lower expression scores within the planum temporale using ICA. Our findings implicate dysfunction in rs-fMRI activity in first-episode psychosis prior to extensive antipsychotic treatment using different analytic approaches (in the absence of concomitant gray matter structural differences) that predict processing speed. PMID:25567423

  20. Nanotools for Neuroscience and Brain Activity Mapping

    PubMed Central

    Alivisatos, A. Paul; Andrews, Anne M.; Boyden, Edward S.; Chun, Miyoung; Church, George M.; Deisseroth, Karl; Donoghue, John P.; Fraser, Scott E.; Lippincott-Schwartz, Jennifer; Looger, Loren L.; Masmanidis, Sotiris; McEuen, Paul L.; Nurmikko, Arto V.; Park, Hongkun; Peterka, Darcy S.; Reid, Clay; Roukes, Michael L.; Scherer, Axel; Schnitzer, Mark; Sejnowski, Terrence J.; Shepard, Kenneth L.; Tsao, Doris; Turrigiano, Gina; Weiss, Paul S.; Xu, Chris; Yuste, Rafael; Zhuang, Xiaowei

    2013-01-01

    Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function. PMID:23514423

  1. Telomerase activity in 144 brain tumours.

    PubMed Central

    Sano, T.; Asai, A.; Mishima, K.; Fujimaki, T.; Kirino, T.

    1998-01-01

    Unlimited proliferation in immortalized cells is believed to be highly dependent on the activity of telomerase, a ribonucleoprotein that synthesizes telomeric repeats onto chromosome ends. Using a polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay, we analysed telomerase activity in 99 benign and 45 malignant brain tumours. The TRAP assay results were quantitated by normalizing the telomerase activity of each specimen to that of human glioma cell line T98G to obtain the relative telomerase activity. Telomerase activity was also assessed visually from the autoradiograms as being positive or negative. One hundred and sixteen tumours with negative telomerase activity had null relative telomerase activity, whereas 28 tumours with positive telomerase activity had relative telomerase activities of 12-84.3% (mean 0% vs 36.1 +/- 19.3%, P < 0.0001). Thus, quantification of telomerase activity confirmed the results of the visual evaluation of telomerase activity on autoradiograms. Based on the assessment, malignant brain tumours had a higher positive rate of telomerase activity than benign tumours (57.8% vs 2.0%, P < 0.001). These data indicate that positive telomerase activity is strongly associated with malignant brain tumours and is rather rare in benign tumours, such as neurinomas or meningiomas. Images Figure 2 PMID:9635839

  2. Glucose Metabolism during Resting State Reveals Abnormal Brain Networks Organization in the Alzheimer’s Disease and Mild Cognitive Impairment

    PubMed Central

    Martínez-Montes, Eduardo

    2013-01-01

    This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network’s attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI. PMID:23894356

  3. Brain MRI abnormalities in the adult form of myotonic dystrophy type 1: A longitudinal case series study.

    PubMed

    Conforti, Renata; de Cristofaro, Mario; Cristofano, Adriana; Brogna, Barbara; Sardaro, Angela; Tedeschi, Gioacchino; Cirillo, Sossio; Di Costanzo, Alfonso

    2016-02-01

    This study aimed to verify whether brain abnormalities, previously described in patients with myotonic dystrophy type 1 (DM1) by magnetic resonance imaging (MRI), progressed over time and, if so, to characterize their progression. Thirteen DM1 patients, who had at least two MRI examinations, were retrospectively evaluated and included in the study. The mean duration (± standard deviation) of follow-up was 13.4 (±3.8) years, over a range of 7-20 years. White matter lesions (WMLs) were rated by semi-quantitative method, the signal intensity of white matter poster-superior to trigones (WMPST) by reference to standard images and brain atrophy by ventricular/brain ratio (VBR). At the end of MRI follow-up, the scores relative to lobar, temporal and periventricular WMLs, to WMPST signal intensity and to VBR were significantly increased compared to baseline, and MRI changes were more evident in some families than in others. No correlation was found between the MRI changes and age, onset, disease duration, muscular involvement, CTG repetition and follow-up duration. These results demonstrated that white matter involvement and brain atrophy were progressive in DM1 and suggested that progression rate varied from patient to patient, regardless of age, disease duration and genetic defect. PMID:26755488

  4. Heritability of working memory brain activation.

    PubMed

    Blokland, Gabriëlla A M; McMahon, Katie L; Thompson, Paul M; Martin, Nicholas G; de Zubicaray, Greig I; Wright, Margaret J

    2011-07-27

    Although key to understanding individual variation in task-related brain activation, the genetic contribution to these individual differences remains largely unknown. Here we report voxel-by-voxel genetic model fitting in a large sample of 319 healthy, young adult, human identical and fraternal twins (mean ± SD age, 23.6 ± 1.8 years) who performed an n-back working memory task during functional magnetic resonance imaging (fMRI) at a high magnetic field (4 tesla). Patterns of task-related brain response (BOLD signal difference of 2-back minus 0-back) were significantly heritable, with the highest estimates (40-65%) in the inferior, middle, and superior frontal gyri, left supplementary motor area, precentral and postcentral gyri, middle cingulate cortex, superior medial gyrus, angular gyrus, superior parietal lobule, including precuneus, and superior occipital gyri. Furthermore, high test-retest reliability for a subsample of 40 twins indicates that nongenetic variance in the fMRI brain response is largely due to unique environmental influences rather than measurement error. Individual variations in activation of the working memory network are therefore significantly influenced by genetic factors. By establishing the heritability of cognitive brain function in a large sample that affords good statistical power, and using voxel-by-voxel analyses, this study provides the necessary evidence for task-related brain activation to be considered as an endophenotype for psychiatric or neurological disorders, and represents a substantial new contribution to the field of neuroimaging genetics. These genetic brain maps should facilitate discovery of gene variants influencing cognitive brain function through genome-wide association studies, potentially opening up new avenues in the treatment of brain disorders. PMID:21795540

  5. Memory activation enhances EEG abnormality in mild cognitive impairment.

    PubMed

    van der Hiele, K; Vein, A A; Kramer, C G S; Reijntjes, R H A M; van Buchem, M A; Westendorp, R G J; Bollen, E L E M; van Dijk, J G; Middelkoop, H A M

    2007-01-01

    This exploratory study investigated EEG power changes during memory activation in patients with amnestic mild cognitive impairment (MCI). Twelve MCI patients and 16 age-matched controls underwent EEG registration during two conventional EEG conditions ('eyes closed' and 'eyes open') and three memory conditions ('word memory', 'picture memory' and 'animal fluency'). For all conditions, EEG power in the theta (4-8 Hz), lower alpha (8-10.5 Hz) and upper alpha (10.5-13 Hz) bands were expressed as percentile changes compared to 'eyes closed'. MCI patients showed significantly less decrease in the lower alpha band than controls (p=0.04) during picture memory activation. The word memory task showed a trend towards a similar effect (p=0.09). This study suggests that memory activation reveals EEG differences between MCI patients and controls while conventional EEG conditions do not. PMID:16406153

  6. Abnormal neurological exam findings in individuals with mild traumatic brain injury (mTBI) versus psychiatric and healthy controls.

    PubMed

    Silva, Marc A; Donnell, Alison J; Kim, Michelle S; Vanderploeg, Rodney D

    2012-01-01

    In those with a history of mild traumatic brain injury (mTBI), cognitive and emotional disturbances are often misattributed to that preexisting injury. However, causal determinations of current symptoms cannot be conclusively determined because symptoms are often nonspecific to etiology and offer virtually no differential diagnostic value in postacute or chronic phases. This population-based study examined whether the presence of abnormalities during neurological examination would distinguish between mTBI (in the chronic phase), healthy controls, and selected psychiatric conditions. Retrospective analysis of data from 4462 community-dwelling Army veterans was conducted. Diagnostically unique groups were compared on examination of cranial nerve function and other neurological signs. Results demonstrated that individuals with mTBI were no more likely than those with a major depressive disorder, generalized anxiety disorder, posttraumatic stress disorder, or somatoform disorder to show any abnormality. Thus, like self-reported cognitive and emotional symptoms, the presence of cranial nerve or other neurological abnormalities offers no differential diagnostic value. Clinical implications and study limitations are presented. PMID:23020281

  7. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

    PubMed

    Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Ontiveros, Esperanza; Gómez-Garza, Gilberto; Barragán-Mejía, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R; Henríquez-Roldán, Carlos; Pérez-Guillé, Beatriz; Torres-Jardón, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C; Engle, Randall W

    2008-11-01

    Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children. PMID:18550243

  8. Comparison of nine tractography algorithms for detecting abnormal structural brain networks in Alzheimer’s disease

    PubMed Central

    Zhan, Liang; Zhou, Jiayu; Wang, Yalin; Jin, Yan; Jahanshad, Neda; Prasad, Gautam; Nir, Talia M.; Leonardo, Cassandra D.; Ye, Jieping; Thompson, Paul M.; for the Alzheimer’s Disease Neuroimaging Initiative

    2015-01-01

    Alzheimer’s disease (AD) involves a gradual breakdown of brain connectivity, and network analyses offer a promising new approach to track and understand disease progression. Even so, our ability to detect degenerative changes in brain networks depends on the methods used. Here we compared several tractography and feature extraction methods to see which ones gave best diagnostic classification for 202 people with AD, mild cognitive impairment or normal cognition, scanned with 41-gradient diffusion-weighted magnetic resonance imaging as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) project. We computed brain networks based on whole brain tractography with nine different methods – four of them tensor-based deterministic (FACT, RK2, SL, and TL), two orientation distribution function (ODF)-based deterministic (FACT, RK2), two ODF-based probabilistic approaches (Hough and PICo), and one “ball-and-stick” approach (Probtrackx). Brain networks derived from different tractography algorithms did not differ in terms of classification performance on ADNI, but performing principal components analysis on networks helped classification in some cases. Small differences may still be detectable in a truly vast cohort, but these experiments help assess the relative advantages of different tractography algorithms, and different post-processing choices, when used for classification. PMID:25926791

  9. Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke

    PubMed Central

    Liu, Shuang; Guo, Jie; Meng, Jiayuan; Wang, Zhijun; Yao, Yang; Yang, Jiajia; Qi, Hongzhi; Ming, Dong

    2016-01-01

    Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID:27403202

  10. Deletion in the N-terminal half of olfactomedin 1 modifies its interaction with synaptic proteins and causes brain dystrophy and abnormal behavior in mice.

    PubMed

    Nakaya, Naoki; Sultana, Afia; Munasinghe, Jeeva; Cheng, Aiwu; Mattson, Mark P; Tomarev, Stanislav I

    2013-12-01

    Olfactomedin 1 (Olfm1) is a secreted glycoprotein that is preferentially expressed in neuronal tissues. Here we show that deletion of exons 4 and 5 from the Olfm1 gene, which encodes a 52 amino acid long region in the N-terminal part of the protein, increased neonatal death and reduced body weight of surviving homozygous mice. Magnetic resonance imaging analyses revealed reduced brain volume and attenuated size of white matter tracts such as the anterior commissure, corpus callosum, and optic nerve. Adult Olfm1 mutant mice demonstrated abnormal behavior in several tests including reduced marble digging, elevated plus maze test, nesting activity and latency on balance beam tests as compared with their wild-type littermates. The olfactory system was both structurally and functionally disturbed by the mutation in the Olfm1 gene as shown by functional magnetic resonance imaging analysis and a smell test. Deficiencies of the olfactory system may contribute to the neonatal death and loss of body weight of Olfm1 mutant. Shotgun proteomics revealed 59 candidate proteins that co-precipitated with wild-type or mutant Olfm1 proteins in postnatal day 1 brain. Olfm1-binding targets included GluR2, Cav2.1, teneurin-4 and Kidins220. Modified interaction of Olfm1 with binding targets led to an increase in intracellular Ca(2+) concentration and activation of ERK1/2, MEK1 and CaMKII in the hippocampus and olfactory bulb of Olfm1 mutant mice compared with their wild-type littermates. Excessive activation of the CaMKII and Ras-ERK pathways in the Olfm1 mutant olfactory bulb and hippocampus by elevated intracellular calcium may contribute to the abnormal behavior and olfactory activity of Olfm1 mutant mice. PMID:24095980

  11. Deletion in the N-terminal Half of Olfactomedin 1 Modifies Its Interaction with Synaptic Proteins and Causes Brain Dystrophy and Abnormal Behavior in Mice

    PubMed Central

    Nakaya, Naoki; Sultana, Afia; Munasinghe, Jeeva; Cheng, Aiwu; Mattson, Mark P.; Tomarev, Stanislav I.

    2013-01-01

    Olfactomedin 1 (Olfm1) is a secreted glycoprotein that is preferentially expressed in neuronal tissues. Here we show that deletion of exons 4 and 5 from the Olfm1 gene, which encodes a 52 amino acid long region in the N-terminal part of the protein, increased neonatal death and reduced body weight of surviving homozygous mice. Magnetic resonance imaging analyses revealed reduced brain volume and attenuated size of white matter tracts such as the anterior commissure, corpus callosum, and optic nerve. Adult Olfm1 mutant mice demonstrated abnormal behavior in several tests including reduced marble digging, elevated plus maze test, nesting activity and latency on balance beam tests as compared with their wild-type littermates. The olfactory system was both structurally and functionally disturbed by the mutation in the Olfm1 gene as shown by functional magnetic resonance imaging analysis and a smell test. Deficiencies of the olfactory system may contribute to the neonatal death and loss of body weight of Olfm1 mutant. Shotgun proteomics revealed 59 candidate proteins that co-precipitated with wild-type or mutant Olfm1 proteins in postnatal day 1 brain. Olfm1-binding targets included GluR2, Cav2.1, Teneurin-4 and Kidins220. Modified interaction of Olfm1 with binding targets led to an increase in intracellular Ca2+ concentration and activation of ERK1/2, MEK1 and CaMKII in the hippocampus and olfactory bulb of Olfm1 mutant mice compared with their wild-type littermates. Excessive activation of the CaMKII and Ras-ERK pathways in the Olfm1 mutant olfactory bulb and hippocampus by elevated intracellular calcium may contribute to the abnormal behavior and olfactory activity of Olfm1 mutant mice. PMID:24095980

  12. [Synchronized, oscillatory brain activity in visual perception].

    PubMed

    Braunitzer, Gábor

    2008-09-30

    The present study investigates one of the most promising developments of the brain-mind question, namely the possible links between synchronized oscillatory brain activity and certain (visual) perceptual processes. Through a review of the relevant literature, the author introduces the reader to the most important theories of coherent perception ('binding'), and makes an attempt to show how synchronization of EEG-registrable oscillatory activities from various frequency bands might explain binding. Finally, a number of clinical problems are also mentioned, regarding which the presented theoretical framework might deserve further consideration. PMID:18841649

  13. Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

    PubMed Central

    Chen, Lizhou; Huang, Xiaoqi; Lei, Du; He, Ning; Hu, Xinyu; Chen, Ying; Li, Yuanyuan; Zhou, Jinbo; Guo, Lanting; Kemp, Graham J.; Gong, Qiyong

    2015-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. Methods We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. Results Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. Limitations This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. Conclusion Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD. PMID:25853285

  14. 3D PATTERN OF BRAIN ABNORMALITIES IN WILLIAMS SYNDROME VISUALIZED USING TENSOR-BASED MORPHOMETRY

    PubMed Central

    Chiang, Ming-Chang; Reiss, Allan L.; Lee, Agatha D.; Bellugi, Ursula; Galaburda, Albert M.; Korenberg, Julie R.; Mills, Debra L.; Toga, Arthur W.; Thompson, Paul M.

    2009-01-01

    Williams syndrome (WS) is a neurodevelopmental disorder associated with deletion of ~20 contiguous genes in chromosome band 7q11.23. Individuals with WS exhibit mild to moderate mental retardation, but are relatively more proficient in specific language and musical abilities. We used tensor-based morphometry (TBM) to visualize the complex pattern of gray/white matter reductions in WS, based on fluid registration of structural brain images. Methods 3D T1-weighted brain MRIs of 41 WS subjects (age: 29.2±9.2SD years; 23F/18M) and 39 age-matched healthy controls (age: 27.5±7.4 years; 23F/16M) were fluidly registered to a minimum deformation target. Fine-scale volumetric differences were mapped between diagnostic groups. Local regions were identified where regional structure volumes were associated with diagnosis, and with intelligence quotient (IQ) scores. Brain asymmetry was also mapped and compared between diagnostic groups. Results WS subjects exhibited widely distributed brain volume reductions (~10–15% reduction; P < 0.0002, permutation test). After adjusting for total brain volume, the frontal lobes, anterior cingulate, superior temporal gyrus, amygdala, fusiform gyrus and cerebellum were found to be relatively preserved in WS, but parietal and occipital lobes, thalamus and basal ganglia, and midbrain were disproportionally decreased in volume (P < 0.0002). These regional volumes also correlated positively with performance IQ in adult WS subjects (age ≥ 30 years, P = 0.038). Conclusion TBM facilitates 3D visualization of brain volume reductions in WS. Reduced parietal/occipital volumes may be associated with visuospatial deficits in WS. By contrast, frontal lobes, amygdala, and cingulate gyrus are relatively preserved or even enlarged, consistent with unusual affect regulation and language production in WS. PMID:17512756

  15. Predictors of Abnormal Neuroimaging of the Brain in Children With Epilepsy Aged 1 Month to 2 Years: Useful Clues in a Resource-Limited Setting.

    PubMed

    Sanmaneechai, Oranee; Danchaivijitr, Nasuda; Likasitwattanakul, Surachai

    2015-10-01

    Neuroimaging should be performed on infants with seizure. However, there are economic limitations in performing neuroimaging in a resource-limited setting. The younger the age, the higher the risk of having abnormal neuroimaging. The aim was to determine frequency and predictors of abnormal neuroimaging in children with epilepsy aged 1 month to 2 years. History, physical examination, electroencephalogram (EEG), and neuroimaging were reviewed. Thirty-seven of 49 (76%) had neuroimaging studies; 19 computed tomography (CT), 14 magnetic resonance imaging (MRI), and 4 had both. Abnormal neuroimaging was found in 19 (51%). Predictors of abnormal neuroimages are developmental delay, abnormal head circumference, and abnormal neurologic examination. Eight children (21%) had lesions on neuroimaging studies that altered or influenced management. Of 8 patients with normal examination and EEG, 1 had a brain tumor and another had arteriovenous malformation. Neuroimaging should be considered as an essential aid in the evaluation of infants with epilepsy, even in a resource-limited setting. PMID:25792429

  16. White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

    PubMed

    Miller, Danielle R; Hayes, Jasmeet P; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS. PMID:26497829

  17. Diagnostic yield and accuracy of postmortem cytological sampling from the brain surface of animals with neurological abnormalities.

    PubMed

    Wünsche, S; Rosati, M; Matiasek, K

    2016-05-01

    Clarification of central nervous system (CNS) disorders frequently requires pathological investigation via brain biopsy or postmortem examination. The use of cytology is usually restricted to diagnosis of mass lesions and septic meningitis. The value of brain cytology at postmortem examination has not been explored sufficiently. This study aimed to clarify the diagnostic value of meningeal imprint cytology at postmortem brain examination. Samples were taken from cerebrum and cerebellum and stained with the modified Wright stain and with haematoxylin-eosin. The slides were evaluated and findings were compared to brain histopathology with respect to resemblance, discrepancy and diagnostic validity. The study included 169 cases involving multiple animal species. Histopathology identified inflammatory disorders in 60/135 (44.4%) cases, neoplasia in 19/135 (14.1%) and non-infiltrative diseases in 56/135 (41.5%). Cytology revealed pathological changes in 79/135 (58.5%) of these cases. The histopathological diagnosis was reproduced in 57/135 (42.2%) cases, 43/57 (75.4%) of which were inflammatory. Non-diagnostic cases included 16/135 (11.9%) with sub-diagnostic cytological features and 3/135 (2.2%) with unclear phenomena. In 55/135 (40.7%) of brains with histological lesions, cytology proved inferior, providing negative results, including 40/55 (72.7%) cases with non-infiltrative diseases, 12/55 (21.8%) with inflammation and 3/55 (5.5%) with neoplasia. Conversely, 3/34 (8.8%) of controls showed cytological abnormalities. Cytological sampling from CNS adds to the sensitivity of neuropathological investigations, even if restricted to non-invasive surface imprints. The diagnostic accuracy exceeds 40%, with infiltrative diseases being five times more likely to be detected than non-infiltrative diseases. PMID:27009475

  18. Abnormal Functional MRI BOLD Contrast in the Vegetative State after Severe Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Heelmann, Volker

    2010-01-01

    For the rehabilitation process, the treatment of patients surviving brain injury in a vegetative state is still a serious challenge. The aim of this study was to investigate patients exhibiting severely disturbed consciousness using functional magnetic resonance imaging. Five cases of posttraumatic vegetative state and one with minimal…

  19. Tobacco Smoking and MRI/MRS Brain Abnormalities Compared to Nonsmokers

    PubMed Central

    Domino, E.F.

    2008-01-01

    This mini review emphasizes the fact that tobacco smoking causes small but real biologic brain changes that need to be studied in depth. A crucial question is whether these anatomical/chemical changes reverse toward normal when smokers quit. This review is presented to stimulate further research to answer this question. PMID:18817837

  20. Air Pollution, Cognitive Deficits and Brain Abnormalities: A Pilot Study with Children and Dogs

    ERIC Educational Resources Information Center

    Calderon-Garciduenas, Lilian; Mora-Tiscareno, Antonieta; Ontiveros, Esperanza; Gomez-Garza, Gilberto; Barragan-Mejia, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R.; Henriquez-Roldan, Carlos; Perez-Guille, Beatriz; Torres-Jardon, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E.; Gonzalez-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C.; Engle, Randall W.

    2008-01-01

    Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n:55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic…

  1. Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment

    ERIC Educational Resources Information Center

    Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

  2. Brief Report: Abnormal Association between the Thalamus and Brain Size in Asperger's Disorder

    ERIC Educational Resources Information Center

    Hardan, Antonio Y.; Girgis, Ragy R.; Adams, Jason; Gilbert, Andrew R.; Melhem, Nadine M.; Keshavan, Matcheri S.; Minshew, Nancy J.

    2008-01-01

    The objective of this study was to examine the relationship between thalamic volume and brain size in individuals with Asperger's disorder (ASP). Volumetric measurements of the thalamus were performed on MRI scans obtained from 12 individuals with ASP (age range: 10-35 years) and 12 healthy controls (age range: 9-33 years). A positive correlation…

  3. Brain metabolite concentrations are associated with illness severity scores and white matter abnormalities in very preterm infants

    PubMed Central

    Card, Dallas; Nossin-Manor, Revital; Moore, Aideen M.; Raybaud, Charles; Sled, John G.; Taylor, Margot J.

    2016-01-01

    Background Magnetic resonance spectroscopy allows for the noninvasive study of brain metabolism and therefore may provide useful information about brain injuries. We examined the associations of brain metabolite ratios in very preterm infants with white matter lesions and overall health status at birth. Methods Spectroscopy data were obtained from 99 very preterm infants (born ≤32wk gestation) imaged shortly after birth and from 67 of these infants at term-equivalent age. These data were processed using LC Model. Multiple regression was used to examine the association of metabolite ratios with focal non cystic white matter lesions visible on conventional magnetic resonance imaging (MRI) and with at-birth illness severity scores. Results Within 2wk of birth, the ratio of N-acetylaspartate + N-acetylaspartylglutamate to creatine + phosphocreatine was significantly lower in those infants showing white matter abnormalities on conventional MRI. Increased lactate to creatine + phosphocreatine and lactate to glycerophosphocholine + phosphocholine ratios were significantly associated with increasing severity of Clinical Risk Index for Babies II and Apgar scores taken at 1 and 5min after birth. Conclusion Both overall health status at birth and white matter injury in preterm neonates are reflected in metabolite ratios measured shortly after birth. Long-term follow-up will provide additional insight into the prognostic value of these measures. PMID:23575877

  4. Structural and functional brain abnormalities place phenocopy frontotemporal dementia (FTD) in the FTD spectrum

    PubMed Central

    Steketee, Rebecca M.E.; Meijboom, Rozanna; Bron, Esther E.; Osse, Robert Jan; de Koning, Inge; Jiskoot, Lize C.; Klein, Stefan; de Jong, Frank Jan; van der Lugt, Aad; van Swieten, John C.; Smits, Marion

    2016-01-01

    Purpose ‘Phenocopy’ frontotemporal dementia (phFTD) patients may clinically mimic the behavioral variant of FTD (bvFTD), but do not show functional decline or abnormalities upon visual inspection of routine neuroimaging. We aimed to identify abnormalities in gray matter (GM) volume and perfusion in phFTD and to assess whether phFTD belongs to the FTD spectrum. We compared phFTD patients with both healthy controls and bvFTD patients. Materials & methods Seven phFTD and 11 bvFTD patients, and 20 age-matched controls underwent structural T1-weighted magnetic resonance imaging (MRI) and 3D pseudo-continuous arterial spin labeling (pCASL) at 3T. Normalized GM (nGM) volumes and perfusion, corrected for partial volume effects, were quantified regionally as well as in the entire supratentorial cortex, and compared between groups taking into account potential confounding effects of gender and scanner. Results PhFTD patients showed cortical atrophy, most prominently in the right temporal lobe. Apart from this regional atrophy, GM volume was generally not different from either controls or from bvFTD. BvFTD however showed extensive frontotemporal atrophy. Perfusion was increased in the left prefrontal cortex compared to bvFTD and to a lesser extent to controls. Conclusion PhFTD and bvFTD show overlapping cortical structural abnormalities indicating a continuum of changes especially in the frontotemporal regions. Together with functional changes suggestive of a compensatory response to incipient pathology in the left prefrontal regions, these findings are the first to support a possible neuropathological etiology of phFTD and suggest that phFTD may be a neurodegenerative disease on the FTD spectrum. PMID:27222795

  5. Modulation of Brain Activity during Phonological Familiarization

    ERIC Educational Resources Information Center

    Majerus, S.; Van der Linden, M.; Collette, F.; Laureys, S.; Poncelet, M.; Degueldre, C.; Delfiore, G.; Luxen, A.; Salmon, E.

    2005-01-01

    We measured brain activity in 12 adults for the repetition of auditorily presented words and nonwords, before and after repeated exposure to their phonological form. The nonword phoneme combinations were either of high (HF) or low (LF) phonotactic frequency. After familiarization, we observed, for both word and nonword conditions, decreased…

  6. Altered Spontaneous Brain Activity in Betel Quid Dependence

    PubMed Central

    Liu, Tao; Li, Jian-jun; Zhao, Zhong-yan; Yang, Guo-shuai; Pan, Meng-jie; Li, Chang-qing; Pan, Su-yue; Chen, Feng

    2016-01-01

    Abstract It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate. In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate. The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals. PMID

  7. Brain gene expression differences are associated with abnormal tail biting behavior in pigs.

    PubMed

    Brunberg, E; Jensen, P; Isaksson, A; Keeling, L J

    2013-03-01

    Knowledge about gene expression in animals involved in abnormal behaviors can contribute to the understanding of underlying biological mechanisms. This study aimed to explore the motivational background to tail biting, an abnormal injurious behavior and severe welfare problem in pig production. Affymetrix microarrays were used to investigate gene expression differences in the hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving bites to the tail and neutral pigs who were not involved in the behavior. In the hypothalamus, 32 transcripts were differentially expressed (P < 0.05) when tail biters were compared with neutral pigs, 130 when comparing receiver pigs with neutrals, and two when tail biters were compared with receivers. In the prefrontal cortex, seven transcripts were differently expressed in tail biters when compared with neutrals, seven in receivers vs. neutrals and none in the tail biters vs. receivers. In total, 19 genes showed a different expression pattern in neutral pigs when compared with both performers and receivers. This implies that the functions of these may provide knowledge about why the neutral pigs are not involved in tail biting behavior as performers or receivers. Among these 19 transcripts were genes associated with production traits in pigs (PDK4), sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These are in line with hypotheses linking tail biting with reduced back fat thickness and explorative behavior. PMID:23146156

  8. Electromagnetic imaging of dynamic brain activity

    SciTech Connect

    Mosher, J.; Leahy, R. . Dept. of Electrical Engineering); Lewis, P.; Lewine, J.; George, J. ); Singh, M. . Dept. of Radiology)

    1991-01-01

    Neural activity in the brain produces weak dynamic electromagnetic fields that can be measured by an array of sensors. Using a spatio-temporal modeling framework, we have developed a new approach to localization of multiple neural sources. This approach is based on the MUSIC algorithm originally developed for estimating the direction of arrival of signals impinging on a sensor array. We present applications of this technique to magnetic field measurements of a phantom and of a human evoked somatosensory response. The results of the somatosensory localization are mapped onto the brain anatomy obtained from magnetic resonance images.

  9. Electromagnetic imaging of dynamic brain activity

    SciTech Connect

    Mosher, J.; Leahy, R.; Lewis, P.; Lewine, J.; George, J.; Singh, M.

    1991-12-31

    Neural activity in the brain produces weak dynamic electromagnetic fields that can be measured by an array of sensors. Using a spatio-temporal modeling framework, we have developed a new approach to localization of multiple neural sources. This approach is based on the MUSIC algorithm originally developed for estimating the direction of arrival of signals impinging on a sensor array. We present applications of this technique to magnetic field measurements of a phantom and of a human evoked somatosensory response. The results of the somatosensory localization are mapped onto the brain anatomy obtained from magnetic resonance images.

  10. Complex networks in brain electrical activity

    NASA Astrophysics Data System (ADS)

    Ray, C.; Ruffini, G.; Marco-Pallarés, J.; Fuentemilla, L.; Grau, C.

    2007-08-01

    This letter reports a method to extract a functional network of the human brain from electroencephalogram measurements. A network analysis was performed on the resultant network and the statistics of the cluster coefficient, node degree, path length, and physical distance of the links, were studied. Even given the low electrode count of the experimental data the method was able to extract networks with network parameters that clearly depend on the type of stimulus presented to the subject. This type of analysis opens a door to studying the cerebral networks underlying brain electrical activity, and links the fields of complex networks and cognitive neuroscience.

  11. Abnormal Cortical Development after Premature Birth Shown by Altered Allometric Scaling of Brain Growth

    PubMed Central

    Kapellou, Olga; Counsell, Serena J; Kennea, Nigel; Dyet, Leigh; Saeed, Nadeem; Stark, Jaroslav; Maalouf, Elia; Duggan, Philip; Ajayi-Obe, Morenike; Hajnal, Jo; Allsop, Joanna M; Boardman, James; Rutherford, Mary A; Cowan, Frances; Edwards, A. David

    2006-01-01

    Background We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment. Methods and Findings We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25–1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth. Conclusions Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery. PMID:16866579

  12. Cross-sectional and longitudinal abnormalities in brain structure in children with severe mood dysregulation or bipolar disorder

    PubMed Central

    Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

    2012-01-01

    Background There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in bipolar disorder (BD) have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time. Furthermore, the developmental trajectories of structural abnormalities in BD or SMD are unknown. This study provides such data in BD, SMD, and HV. Methods An optimized, modulated voxel-based morphometry (VBM) analysis was conducted on structural MRI scans from 201 children (78 SMD, 55 BD, and 68 HV). Additionally, 92 children (31 SMD, 34 BD, and 27 HV) were re-scanned after two years (mean interval 1.99 ± 0.94 years), to compare time-related changes among the three groups. Results Cross-sectionally, the groups differed in gray matter (GM) volume in pre-supplementary motor area (pre-SMA), dorsolateral prefrontal cortex (DLPFC), insula, and globus pallidus. The cortical differences were driven mainly by increased GM volume in HV compared to BD and SMD. In globus pallidus, there was increased GM in BD compared to HV and SMD. Longitudinally, group-by-time interactions were evident in two clusters in the superior/inferior parietal lobule (R SPL/IPL) and in the precuneus. In both clusters, the interactions were driven by an abnormal increase in volume in BD. Conclusions Cross-sectionally, both BD and SMD are associated with structural abnormalities in frontal cortex, insula, and basal ganglia. While some of these deficits overlap (insula and DLPFC), others differentiate SMD and BD (pre-SMA and globus pallidus). Abnormal developmental trajectories in lateral parietal cortex and precuneus are present in, and unique to, BD. Because of the high proportion of co-occurring ADHD in the SMD subjects, we could not separate effects of ADHD from those of SMD, and future research including a non-irritable ADHD group must

  13. Quantitative observation and study on rhythmic abnormalities of activities in animals prior to earthquakes

    NASA Astrophysics Data System (ADS)

    Feng, Chungao; Jiang, Jinchang

    1992-11-01

    In this paper, the normal daily activities and abnormal activities related to earthquake premonitory information are given by a quantitative observation and analysis of activities in the sparrow (SR, Passer montanus), budgerigar (BG, Melopsittacus undulatus) and rat (RT, Rattus norvegicus). The results show that the quantitative observation of habitual abnormalities in animals may provide some cues for the short-term earthquake prediction. The normal activity rhythms for the SR and BG are similar, and both present M mode. The high activities occurs during 07h 10h and 15h 16h, respectively, the low activities occurs during 12h 13h, and at night both birds are basically silent. For the RT, the normal rhythmic activity has the middle magnitude during 07h 10h and 17h 18h, the low and high magnitudes occur during 11h 16h and from 19h to 06h at the next day. For the SR, BG and RT, observable abnormal changes of the normal activity rhythm were found before earthquakes. The night activities of the SR and BG were increased noticeably. For the RT the activities during the low magnitude of activities at the day time were also increased. They both are about 300 times greater than the normal activity value. Moreover, the total activity values per day were increased, and were about 2 times of the normal value. The x 2-test shows that the abnormalities of the daily activity rhythm and following increase of the daily activity events are significantly correlated with earthquakes of magnitude over 4.3 in Tangshan seismic area within the region of 200 km distance from the observation station.

  14. Differential Impact of Hyponatremia and Hepatic Encephalopathy on Health-Related Quality of Life and Brain Metabolite Abnormalities in Cirrhosis

    PubMed Central

    Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, HoChong; Heuman, Douglas M; Bajaj, Jasmohan S

    2013-01-01

    Background Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality-of-life (HRQOL) and cognition in cirrhosis. Aim To study effect of hyponatremia on cognition, HRQOL and brain MR spectroscopy (MRS) independent of HE. Methods Four cirrhotic groups(no HE/HN, HE alone, HN alone (sodium<130mEq/L),HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psycho-social and physical sub-scores) and brain MRS (myoinositol(mI) and glutamate+glutamine(Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. Results 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN and 10 HN, MELD 12, 63% Hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN:3, HN:3.5, HE:6.5,HE+HN:7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP(p<0.0001, all comparisons). Brain MRS showed lowest Glx in HN and highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE,HE+HN and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psycho-social SIP scores. Conclusions Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. PMID:23665182

  15. Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter.

    PubMed Central

    DeCarli, C; Grady, C L; Clark, C M; Katz, D A; Brady, D R; Murphy, D G; Haxby, J V; Salerno, J A; Gillette, J A; Gonzalez-Aviles, A; Rapoport, S I

    1996-01-01

    OBJECTIVES--To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). METHODS--Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. RESULTS--Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no

  16. Regional homogeneity of resting-state brain abnormalities in violent juvenile offenders: a biomarker of brain immaturity?

    PubMed

    Chen, Chen; Zhou, Jiansong; Liu, Chunhong; Witt, Katrina; Zhang, Yingdong; Jing, Bin; Li, Chun; Wang, Xiaoping; Li, Lingjiang

    2015-01-01

    The authors investigated whether male violent juvenile offenders demonstrate any differences in local functional connectivity indicative of delayed maturation of the brain that may serve as a biomarker of violence. Twenty-nine violent juvenile offenders and 28 age-matched controls were recruited. Regional homogeneity (ReHo) method was used to analyze resting-state magnetic resonance images. Violent offenders showed significantly lower ReHo values in the right caudate, right medial prefrontal cortex, and left precuneus, and higher values in the right supramarginal gyrus than the controls. These regions had both high sensitivity and specificity in distinguishing between the two groups suggesting that dysfunction in these regions can be used to correctly classify those individuals who are violent. Dysfunction in the right medial prefrontal-caudate circuit may, therefore, represent an important biomarker of violence juvenile males. PMID:25716485

  17. Asymmetric Di-methyl Arginine is Strongly Associated with Cognitive Dysfunction and Brain MR Spectroscopic Abnormalities in Cirrhosis

    PubMed Central

    Bajaj, Jasmohan S; Ahluwalia, Vishwadeep; Wade, James B; Sanyal, Arun J; White, Melanie B; Noble, Nicole A; Monteith, Pamela; Fuchs, Michael; Sterling, Richard K; Luketic, Velimir; Bouneva, Iliana; Stravitz, Richard T; Puri, Puneet; Kraft, Kenneth A; Gilles, HoChong; Heuman, Douglas M

    2012-01-01

    Background Asymmetric di-methyl arginine (ADMA) is an inhibitor of nitric oxide synthase that accumulates in liver disease and may contribute to hepatic encephalopathy(HE). Aim To evaluate the association of ADMA with cognition and brain MR spectroscopy(MRS) in cirrhosis. Methods Cirrhotic patients with/without prior HE and non-cirrhotic controls underwent cognitive testing and ADMA determination. A subgroup underwent brain MRS [Glutamine/glutamate(Glx), myoinositol(mI), N-acetyl-aspartate(NAA) in parietal white, occipital gray and anterior cingulate(ACC)]. We also tested cognition and ADMA in a cirrhotic subgroup before and 1 month after transjugular intrahepatic portosystemic shunting (TIPS). Cognition and MRS values were correlated with ADMA and compared between groups using multi-variable regression. ADMA levels were compared between those who did/did not develop post-TIPS HE. Results 90 cirrhotics (MELD13, 54 prior HE) and 16 controls were included. Controls had better cognition and lower ADMA, Glx and higher mI compared to cirrhotics. Prior HE patients had worse cognition, higher ADMA and Glx and lower mI compared to non-HE cirrhotics. ADMA was positively correlated with MELD (r=0.58,p<0.0001), abnormal cognitive test number(r=0.66,p<0.0001) and Glx and NAAA (white matter,ACC) and negatively with mI. On regression, ADMA predicted number of abnormal tests and mean Z-score independent of prior HE and MELD. 12 patients underwent TIPS;7 developed HE post-TIPS. ADMA increased post-TIPS in patients who developed HE(p=0.019) but not in others(p=0.89). Conclusions A strong association of ADMA with cognition and prior HE was found independent of MELD score in cirrhosis. PMID:22889958

  18. Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance.

    PubMed

    Minkova, Lora; Eickhoff, Simon B; Abdulkadir, Ahmed; Kaller, Christoph P; Peter, Jessica; Scheller, Elisa; Lahr, Jacob; Roos, Raymund A; Durr, Alexandra; Leavitt, Blair R; Tabrizi, Sarah J; Klöppel, Stefan

    2016-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel-based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre-specified motor, working memory, cognitive flexibility, and social-affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre-HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre-HD were observed, but increased positive correlations were evident for mHD, relative to pre-HD and HC. These findings could be explained by a HD-related neuronal loss heterogeneously affecting the examined network at the pre-HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow-up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs. PMID:26453902

  19. Apathy is associated with white matter abnormalities in anterior, medial brain regions in persons with HIV infection

    PubMed Central

    Kamat, Rujvi; Brown, Gregory G.; Bolden, Khalima; Fennema-Notestine, Christine; Archibald, Sarah; Marcotte, Thomas D.; Letendre, Scott L.; Ellis, Ronald J.; Woods, Steven Paul; Grant, Igor; Heaton, Robert K.

    2015-01-01

    Apathy is a relatively common psychiatric syndrome in HIV infection, but little is known about its neural correlates. In the present study, we examined the associations between apathy and diffusion tensor imaging (DTI) indices in key frontal white matter regions in the thalamocorticostriatal circuit that has been implicated in the expression of apathy. Nineteen participants with HIV infection and 19 demographically comparable seronegative comparison subjects completed the Apathy subscale of the Frontal Systems Behavioral Scale as a part of a comprehensive neuropsychiatric research evaluation. When compared to the seronegative participants, the HIV+ group had significantly more frontal white matter abnormalities. Within HIV+ persons, and as predicted, higher ratings of apathy were associated with greater white matter alterations in the anterior corona radiata, genu, and orbital medial prefrontal cortex. The associations between white matter alterations and apathy were independent of depression and were stronger among participants with lower current CD4 counts. All told, these findings indicate that apathy is independently associated with white matter abnormalities in anterior, medial brain regions in persons infected with HIV, particularly in the setting of lower current immune functioning, which may have implications for antiretroviral therapy. PMID:25275424

  20. Steroid abnormalities and the developing brain: Declarative memory for emotionally arousing and neutral material in children with congenital adrenal hyperplasia

    PubMed Central

    Maheu, Françoise S.; Merke, Deborah P.; Schroth, Elizabeth A.; Keil, Margaret F.; Hardin, Julie; Poeth, Kaitlin; Pine, Daniel S.; Ernst, Monique

    2008-01-01

    Summary Steroid hormones modulate memory in animals and human adults. Little is known on the developmental effect of these hormones on the neural networks underlying memory. Using Congenital Adrenal Hyperplasia (CAH) as a naturalistic model of early steroid abnormalities, this study examines the consequences of CAH on memory and its neural correlates for emotionally arousing and neutral material in children. Seventeen patients with CAH and 17 age- and sex-matched healthy children (ages 12 to 14 years) completed the study. Subjects were presented positive, negative and neutral pictures. Memory recall occurred about 30 minutes after viewing the pictures. Children with CAH showed memory deficits for negative pictures compared to healthy children (p < 0.01). There were no group differences on memory performance for either positive or neutral pictures (p’s >0.1). In patients, 24h urinary-free cortisol levels (reflecting glucocorticoid replacement therapy) and testosterone levels were not associated with memory performance. These findings suggest that early steroid imbalances affect memory for negative material in children with CAH. Such memory impairments may result from abnormal brain organization and function following hormonal dysfunction during critical periods of development. PMID:18162329

  1. Intracranial Intra-arachnoid Diverticula and Cyst-like Abnormalities of the Brain.

    PubMed

    Platt, Simon; Hicks, Jill; Matiasek, Lara

    2016-03-01

    Primary intracranial cystic or cyst-like lesions include intra-arachnoid, epidermoid, dermoid, and choroid plexus cysts. Differentiation of these cystic lesions can usually be accomplished by imaging studies alone; however, some cysts are similar in appearance and require histopathology for definitive diagnosis. Clinical signs often reflect the location of the cysts within the intracranial cavity rather than the type of cyst. If clinical signs are significant and progressive, surgical removal is warranted and may be successful, although cystic contents could be harmful if allowed to contact surrounding brain parenchyma or meninges. PMID:26704659

  2. Post mTBI fatigue is associated with abnormal brain functional connectivity

    PubMed Central

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants’ fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject’s fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  3. Post mTBI fatigue is associated with abnormal brain functional connectivity.

    PubMed

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  4. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. PMID:26796967

  5. Values-Oriented Public Policy Forums: Active Learning in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Hevern, Vincent W.

    Students in an undergraduate course in abnormal psychology annually employ a cooperative active learning model to conduct a 4- to 6-day, values-oriented public policy forum (PPF) within the class itself on a general topic of concern to the field of mental health. A comprehensive and structured five-phase model for a PPF is detailed for course…

  6. A small number of abnormal brain connections predicts adult autism spectrum disorder

    PubMed Central

    Yahata, Noriaki; Morimoto, Jun; Hashimoto, Ryuichiro; Lisi, Giuseppe; Shibata, Kazuhisa; Kawakubo, Yuki; Kuwabara, Hitoshi; Kuroda, Miho; Yamada, Takashi; Megumi, Fukuda; Imamizu, Hiroshi; Náñez Sr, José E.; Takahashi, Hidehiko; Okamoto, Yasumasa; Kasai, Kiyoto; Kato, Nobumasa; Sasaki, Yuka; Watanabe, Takeo; Kawato, Mitsuo

    2016-01-01

    Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum. PMID:27075704

  7. A small number of abnormal brain connections predicts adult autism spectrum disorder.

    PubMed

    Yahata, Noriaki; Morimoto, Jun; Hashimoto, Ryuichiro; Lisi, Giuseppe; Shibata, Kazuhisa; Kawakubo, Yuki; Kuwabara, Hitoshi; Kuroda, Miho; Yamada, Takashi; Megumi, Fukuda; Imamizu, Hiroshi; Náñez, José E; Takahashi, Hidehiko; Okamoto, Yasumasa; Kasai, Kiyoto; Kato, Nobumasa; Sasaki, Yuka; Watanabe, Takeo; Kawato, Mitsuo

    2016-01-01

    Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum. PMID:27075704

  8. Face inversion superiority in a case of prosopagnosia following congenital brain abnormalities: what can it tell us about the specificity and origin of face-processing mechanisms?

    PubMed

    Schmalzl, Laura; Palermo, Romina; Harris, Irina M; Coltheart, Max

    2009-05-01

    In the current study we describe J.M., a 15-year-old boy with a history of congenital brain abnormalities and concomitant visual-processing impairments. J.M.'s most prominent deficit is his impaired face recognition, but formal testing also revealed deficits in other domains of visual processing. One aspect that emerged from J.M.'s visual-processing assessment was a tendency to focus on local features and to rely on them for the encoding and identification of visual stimuli including geometric figures, objects, words, and inverted faces. In spite of this general tendency, he was impaired on tasks requiring the encoding of local features in upright faces. Moreover, his ability to distinguish between features in upright faces was significantly worse than that for inverted faces, the opposite pattern to that typically found in normal participants. What is it that keeps J.M. from applying his otherwise intact feature-based processing to upright faces? As proposed in previous reports of face inversion superiority in individuals with acquired face recognition impairments, we suggest that J.M.'s "inverted-face inversion effect" speaks for a specialized cognitive system that is mandatorily engaged by upright (but not inverted) faces, even when it is impaired and therefore maladaptive. In addition, since J.M. suffered from congenital brain abnormalities affecting the normal development of his face-processing skills, his performance suggests that specialized and mandatorily activated face-processing mechanisms are not entirely experience dependent, and that they can remain modular during development even if they don't function properly and are therefore maladaptive. PMID:19657795

  9. Facial emotion recognition impairments are associated with brain volume abnormalities in individuals with HIV.

    PubMed

    Clark, Uraina S; Walker, Keenan A; Cohen, Ronald A; Devlin, Kathryn N; Folkers, Anna M; Pina, Matthew J; Tashima, Karen T

    2015-04-01

    Impaired facial emotion recognition abilities in HIV+ patients are well documented, but little is known about the neural etiology of these difficulties. We examined the relation of facial emotion recognition abilities to regional brain volumes in 44 HIV-positive (HIV+) and 44 HIV-negative control (HC) adults. Volumes of structures implicated in HIV-associated neuropathology and emotion recognition were measured on MRI using an automated segmentation tool. Relative to HC, HIV+ patients demonstrated emotion recognition impairments for fearful expressions, reduced anterior cingulate cortex (ACC) volumes, and increased amygdala volumes. In the HIV+ group, fear recognition impairments correlated significantly with ACC, but not amygdala volumes. ACC reductions were also associated with lower nadir CD4 levels (i.e., greater HIV-disease severity). These findings extend our understanding of the neurobiological substrates underlying an essential social function, facial emotion recognition, in HIV+ individuals and implicate HIV-related ACC atrophy in the impairment of these abilities. PMID:25744868

  10. Myoinositol and glutamate complex neurometabolite abnormality after mild traumatic brain injury

    PubMed Central

    Kierans, Andrea S.; Kirov, Ivan I.; Gonen, Oded; Haemer, Gillian; Nisenbaum, Eric; Babb, James S.; Grossman, Robert I.

    2014-01-01

    Objective: To obtain quantitative neurometabolite measurements, specifically myoinositol (mI) and glutamate plus glutamine (Glx), markers of glial and neuronal excitation, in deep gray matter structures after mild traumatic brain injury (mTBI) using proton magnetic resonance spectroscopy (1H-MRS) and to compare these measurements against normal healthy control subjects. Methods: This study approved by the institutional review board is Health Insurance Portability and Accountability Act compliant. T1-weighted MRI and multi-voxel 1H-MRS imaging were acquired at 3 tesla from 26 patients with mTBI an average of 22 days postinjury and from 13 age-matched healthy controls. Two-way analysis of variance was used to compare patients and controls for mean N-acetylaspartate, choline, creatine (Cr), Glx, and mI levels as well as the respective ratios to Cr within the caudate, globus pallidus, putamen, and thalamus. Results: Quantitative putaminal mI was higher in patients with mTBI compared with controls (p = 0.02). Quantitative neurometabolite ratios of putaminal mI and Glx relative to Cr, mI/Cr, and Glx/Cr were also higher among patients with mTBI compared with controls (p = 0.01 and 0.02, respectively). No other differences in neurometabolite levels or ratios were observed in any other brain region evaluated. Conclusion: Increased putaminal mI, mI/Cr, and Glx/Cr in patients after mTBI compared with control subjects supports the notion of a complex glial and excitatory response to injury without concomitant neuronal loss, evidenced by preserved N-acetylaspartate levels in this region. PMID:24401686

  11. Abnormal regional cerebral blood flow found by technetium-99m ethyl cysteinate dimer brain single photon emission computed tomography in systemic lupus erythematosus patients with normal brain MRI findings.

    PubMed

    Chen, J J-H; Yen, R-F; Kao, A; Lin, C-C; Lee, C-C

    2002-11-01

    In this study, technetium-(99m) ethyl cysteinate dimer ((99m)Tc ECD) brain single photon emission computed tomography (SPECT) was used to detect regional cerebral blood flow (rCBF) of the brain in SLE patients with normal brain magnetic resonance imaging (MRI) findings. Twenty female SLE patients were enrolled in this study, divided into two groups. Group 1 consisted of 10 patients with neuropsychiatric manifestations. Group 2 consisted of 10 patients without neuropsychiatric manifestations. All patients had normal brain MRI findings. Another 10 SLE patients with abnormal MRI findings were included as group 3 for comparison. Meanwhile, 10 healthy female volunteers also underwent brain MRI and (99m)Tc ECD brain SPECT for comparison. The scans revealed hypoperfusion lesions in 9/20 (45%) SLE patients, including 7/10 (70%) cases in group 1 and 2/10 (20%) cases in group 2. In contrast, all 10 patients (100%) in group 3 had abnormal (99m)Tc ECD brain SPECT findings. The parietal lobes were the most commonly involved areas. We conclude that (99m)Tc ECD brain SPECT is more sensitive for detecting rCBF changes than is brain MRI in detecting the brain anatomic changes, and may have a diagnostic value in lupus cerebral involvement. However, (99m)Tc ECD brain SPECT may not be indicated for SLE patients with normal MRI and mild neuropsychiatric symptoms/signs, such headaches and dizziness. PMID:12447638

  12. Left Atrial Volumes and Reservoir Function Are Associated With Subclinical Cerebrovascular Disease: The Cardiovascular Abnormalities and Brain Lesions (CABL) Study

    PubMed Central

    Russo, Cesare; Jin, Zhezhen; Liu, Rui; Iwata, Shinichi; Tugcu, Aylin; Yoshita, Mitsuhiro; Homma, Shunichi; Elkind, Mitchell S.V.; Rundek, Tatjana; DeCarli, Charles; Wright, Clinton B.; Sacco, Ralph L.; Di Tullio, Marco R.

    2013-01-01

    Objectives To assess the relationship of left atrial (LA) phasic volumes and LA reservoir function with subclinical cerebrovascular disease in a stroke-free community-based cohort. Background An increase in LA size is associated with cardiovascular events including stroke. However, it is not known whether LA phasic volumes and reservoir function are associated with subclinical cerebrovascular disease. Methods LA minimum (LAVmin) and maximum (LAVmax) volumes, and LA reservoir function, measured as total emptying volume (LAEV) and total emptying fraction (LAEF), were assessed by real-time three-dimensional echocardiography in 455 stroke-free participants from the community-based Cardiovascular Abnormalities and Brain Lesions (CABL) study. Subclinical cerebrovascular disease was assessed as silent brain infarcts (SBI) and white matter hyperintensity volume (WMHV) by brain magnetic resonance imaging (MRI). Results SBI prevalence was 15.4%; mean WMHV was 0.66±0.92%. Participants with SBI showed greater LAVmin (17.1±9.3 vs. 12.5±5.6 ml/m2, p<0.01) and LAVmax (26.6±8.8 vs. 23.3±7.0 ml/m2, p<0.01) compared to those without SBI. LAEV (9.5±3.4 vs. 10.8±3.9 ml/m2, p<0.01) and LAEF (38.7±14.7% vs. 47.0±11.9%, p<0.01) were also reduced in participants with SBI. In univariate analyses, greater LA volumes and smaller reservoir function were significantly associated with greater WMHV. In multivariate analyses, LAVmin remained significantly associated with SBI [adjusted odds ratio (OR) per SD increase: 1.37, 95% confidence intervals (CI) 1.04–1.80, p<0.05] and with WMHV (β=0.12, p<0.01), whereas LAVmax was not independently associated with either. Smaller LAEF was independently associated with SBI (adjusted OR=0.67, 95% CI 0.50–0.90, p<0.01) and WMHV (β=−0.09, p<0.05). Conclusions Greater LA volumes and reduced LA reservoir function are associated with subclinical cerebrovascular disease detected by brain MRI in subjects without history of stroke. LAVmin and LAEF

  13. Targeted training modifies oscillatory brain activity in schizophrenia patients

    PubMed Central

    Popov, Tzvetan G.; Carolus, Almut; Schubring, David; Popova, Petia; Miller, Gregory A.; Rockstroh, Brigitte S.

    2015-01-01

    Effects of both domain-specific and broader cognitive remediation protocols have been reported for neural activity and overt performance in schizophrenia (SZ). Progress is limited by insufficient knowledge of relevant neural mechanisms. Addressing neuronal signal resolution in the auditory system as a mechanism contributing to cognitive function and dysfunction in schizophrenia, the present study compared effects of two neuroplasticity-based training protocols targeting auditory–verbal or facial affect discrimination accuracy and a standard rehabilitation protocol on magnetoencephalographic (MEG) oscillatory brain activity in an auditory paired-click task. SZ were randomly assigned to either 20 daily 1-hour sessions over 4 weeks of auditory–verbal training (N = 19), similarly intense facial affect discrimination training (N = 19), or 4 weeks of treatment as usual (TAU, N = 19). Pre-training, the 57 SZ showed smaller click-induced posterior alpha power modulation than did 28 healthy comparison participants, replicating Popov et al. (2011b). Abnormally small alpha decrease 300–800 ms around S2 improved more after targeted auditory–verbal training than after facial affect training or TAU. The improvement in oscillatory brain dynamics with training correlated with improvement on a measure of verbal learning. Results replicate previously reported effects of neuroplasticity-based psychological training on oscillatory correlates of auditory stimulus differentiation, encoding, and updating and indicate specificity of cortical training effects. PMID:26082889

  14. Physical activity, air pollution and the brain.

    PubMed

    Bos, Inge; De Boever, Patrick; Int Panis, Luc; Meeusen, Romain

    2014-11-01

    This review introduces an emerging research field that is focused on studying the effect of exposure to air pollution during exercise on cognition, with specific attention to the impact on concentrations of brain-derived neurotrophic factor (BDNF) and inflammatory markers. It has been repeatedly demonstrated that regular physical activity enhances cognition, and evidence suggests that BDNF, a neurotrophin, plays a key role in the mechanism. Today, however, air pollution is an environmental problem worldwide and the high traffic density, especially in urban environments and cities, is a major cause of this problem. During exercise, the intake of air pollution increases considerably due to an increased ventilation rate and particle deposition fraction. Recently, air pollution exposure has been linked to adverse effects on the brain such as cognitive decline and neuropathology. Inflammation and oxidative stress seem to play an important role in inducing these health effects. We believe that there is a need to investigate whether the well-known benefits of regular physical activity on the brain also apply when physical activity is performed in polluted air. We also report our findings about exercising in an environment with ambient levels of air pollutants. Based on the latter results, we hypothesize that traffic-related air pollution exposure during exercise may inhibit the positive effect of exercise on cognition. PMID:25119155

  15. Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

    PubMed

    Shoemaker, Ritchie C; House, Dennis; Ryan, James C

    2014-01-01

    Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation

  16. Using Brain Electrical Activity Mapping to Diagnose Learning Disabilities.

    ERIC Educational Resources Information Center

    Torello, Michael, W.; Duffy, Frank H.

    1985-01-01

    Cognitive neuroscience assumes that measurement of brain electrical activity should relate to cognition. Brain Electrical Activity Mapping (BEAM), a non-invasive technique, is used to record changes in activity from one brain area to another and is 80 to 90 percent successful in classifying subjects as dyslexic or normal. (MT)

  17. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia

    PubMed Central

    Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

    2015-01-01

    The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. PMID:26508861

  18. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia.

    PubMed

    Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

    2015-01-01

    The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. PMID:26508861

  19. Solar activity cycle and the incidence of foetal chromosome abnormalities detected at prenatal diagnosis

    NASA Astrophysics Data System (ADS)

    Halpern, Gabrielle J.; Stoupel, Eliahu G.; Barkai, Gad; Chaki, Rina; Legum, Cyril; Fejgin, Moshe D.; Shohat, Mordechai

    1995-06-01

    We studied 2001 foetuses during the period of minimal solar activity of solar cycle 21 and 2265 foetuses during the period of maximal solar activity of solar cycle 22, in all women aged 37 years and over who underwent free prenatal diagnosis in four hospitals in the greater Tel Aviv area. There were no significant differences in the total incidence of chromosomal abnormalities or of trisomy between the two periods (2.15% and 1.8% versus 2.34% and 2.12%, respectively). However, the trend of excessive incidence of chromosomal abnormalities in the period of maximal solar activity suggests that a prospective study in a large population would be required to rule out any possible effect of extreme solar activity.

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

    PubMed

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

    1977-01-01

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

  1. Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL study

    PubMed Central

    Umeda, Satoshi; Harrison, Neil A.; Gray, Marcus A.; Mathias, Christopher J.; Critchley, Hugo D.

    2015-01-01

    Postural tachycardia syndrome (PoTS), a form of dysautonomia, is characterized by orthostatic intolerance, and is frequently accompanied by a range of symptoms including palpitations, lightheadedness, clouding of thought, blurred vision, fatigue, anxiety, and depression. Although the estimated prevalence of PoTS is approximately 5–10 times as common as the better-known condition orthostatic hypotension, the neural substrates of the syndrome are poorly characterized. In the present study, we used magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) applying the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure to examine variation in regional brain structure associated with PoTS. We recruited 11 patients with established PoTS and 23 age-matched normal controls. Group comparison of gray matter volume revealed diminished gray matter volume within the left anterior insula, right middle frontal gyrus and right cingulate gyrus in the PoTS group. We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and post-central gyrus, paracentral lobule and superior frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and depression scores. Together, these findings of structural differences, particularly within insular and cingulate components of the salience network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic control (and interoceptive representation) and increased vulnerability to psychiatric symptoms in PoTS patients. PMID:25852449

  2. Automated Detection of Brain Abnormalities in Neonatal Hypoxia Ischemic Injury from MR Images

    PubMed Central

    Ghosh, Nirmalya; Sun, Yu; Bhanu, Bir; Ashwal, Stephen; Obenaus, Andre

    2014-01-01

    We compared the efficacy of three automated brain injury detection methods, namely symmetry-integrated region growing (SIRG), hierarchical region splitting (HRS) and modified watershed segmentation (MWS) in human and animal magnetic resonance imaging (MRI) datasets for the detection of hypoxic ischemic injuries (HII). Diffusion weighted imaging (DWI, 1.5T) data from neonatal arterial ischemic stroke (AIS) patients, as well as T2-weighted imaging (T2WI, 11.7T, 4.7T) at seven different time-points (1, 4, 7, 10, 17, 24 and 31 days post HII) in rat-pup model of hypoxic ischemic injury were used to check the temporal efficacy of our computational approaches. Sensitivity, specificity, similarity were used as performance metrics based on manual (‘gold standard’) injury detection to quantify comparisons. When compared to the manual gold standard, automated injury location results from SIRG performed the best in 62% of the data, while 29% for HRS and 9% for MWS. Injury severity detection revealed that SIRG performed the best in 67% cases while HRS for 33% data. Prior information is required by HRS and MWS, but not by SIRG. However, SIRG is sensitive to parameter-tuning, while HRS and MWS are not. Among these methods, SIRG performs the best in detecting lesion volumes; HRS is the most robust, while MWS lags behind in both respects. PMID:25000294

  3. The neurological significance of abnormal natural killer cell activity in chronic toxigenic mold exposures.

    PubMed

    Anyanwu, Ebere; Campbell, Andrew W; Jones, Joseph; Ehiri, John E; Akpan, Akpan I

    2003-11-13

    Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC) activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40 degrees C (104 degrees F), cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide range

  4. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model

    PubMed Central

    Takeda, Atsushi; Tamano, Haruna; Nishio, Ryusuke; Murakami, Taku

    2016-01-01

    Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer’s disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency. PMID:27438830

  5. Behavioral Abnormality Induced by Enhanced Hypothalamo-Pituitary-Adrenocortical Axis Activity under Dietary Zinc Deficiency and Its Usefulness as a Model.

    PubMed

    Takeda, Atsushi; Tamano, Haruna; Nishio, Ryusuke; Murakami, Taku

    2016-01-01

    Dietary zinc deficiency increases glucocorticoid secretion from the adrenal cortex via enhanced hypothalamo-pituitary-adrenocortical (HPA) axis activity and induces neuropsychological symptoms, i.e., behavioral abnormality. Behavioral abnormality is due to the increase in glucocorticoid secretion rather than disturbance of brain zinc homeostasis, which occurs after the increase in glucocorticoid secretion. A major target of glucocorticoids is the hippocampus and their actions are often associated with disturbance of glutamatergic neurotransmission, which may be linked to behavioral abnormality, such as depressive symptoms and aggressive behavior under zinc deficiency. Glucocorticoid-mediated disturbance of glutamatergic neurotransmission in the hippocampus is also involved in the pathophysiology of, not only psychiatric disorders, such as depression, but also neurodegenerative disorders, e.g., Alzheimer's disease. The evidence suggests that zinc-deficient animals are models for behavioral and psychological symptoms of dementia (BPSD), as well as depression. To understand validity to apply zinc-deficient animals as a behavioral abnormality model, this paper deals with the effect of antidepressive drugs and herbal medicines on hippocampal dysfunctions and behavioral abnormality, which are induced by enhanced HPA axis activity under dietary zinc deficiency. PMID:27438830

  6. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    PubMed

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing. PMID:26966964

  7. Brain-specific transcriptional regulator T-brain-1 controls brain wiring and neuronal activity in autism spectrum disorders

    PubMed Central

    Huang, Tzyy-Nan; Hsueh, Yi-Ping

    2015-01-01

    T-brain-1 (TBR1) is a brain-specific T-box transcription factor. In 1995, Tbr1 was first identified from a subtractive hybridization that compared mouse embryonic and adult telencephalons. Previous studies of Tbr1−∕− mice have indicated critical roles for TBR1 in the development of the cerebral cortex, amygdala, and olfactory bulb. Neuronal migration and axonal projection are two important developmental features controlled by TBR1. Recently, recurrent de novo disruptive mutations in the TBR1 gene have been found in patients with autism spectrum disorders (ASDs). Human genetic studies have identified TBR1 as a high-confidence risk factor for ASDs. Because only one allele of the TBR1 gene is mutated in these patients, Tbr1+∕− mice serve as a good genetic mouse model to explore the mechanism by which de novo TBR1 mutation leads to ASDs. Although neuronal migration and axonal projection defects of cerebral cortex are the most prominent phenotypes in Tbr1−∕− mice, these features are not found in Tbr1+∕− mice. Instead, inter- and intra-amygdalar axonal projections and NMDAR expression and activity in amygdala are particularly susceptible to Tbr1 haploinsufficiency. The studies indicated that both abnormal brain wiring (abnormal amygdalar connections) and excitation/inhibition imbalance (NMDAR hypoactivity), two prominent models for ASD etiology, are present in Tbr1+∕− mice. Moreover, calcium/calmodulin-dependent serine protein kinase (CASK) was found to interact with TBR1. The CASK–TBR1 complex had been shown to directly bind the promoter of the Grin2b gene, which is also known as Nmdar2b, and upregulate Grin2b expression. This molecular function of TBR1 provides an explanation for NMDAR hypoactivity in Tbr1+∕− mice. In addition to Grin2b, cell adhesion molecules—including Ntng1, Cdh8, and Cntn2—are also regulated by TBR1 to control axonal projections of amygdala. Taken together, the studies of Tbr1 provide an integrated picture of ASD

  8. Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2-3 Years Old Toddlers

    ERIC Educational Resources Information Center

    Xiao, Zhou; Qiu, Ting; Ke, Xiaoyan; Xiao, Xiang; Xiao, Ting; Liang, Fengjing; Zou, Bing; Huang, Haiqing; Fang, Hui; Chu, Kangkang; Zhang, Jiuping; Liu, Yijun

    2014-01-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships…

  9. A case of ataxic diplegia, mental retardation, congenital nystagmus and abnormal auditory brain stem responses showing only waves I and II.

    PubMed

    Aiba, K; Yokochi, K; Ishikawa, T

    1986-01-01

    A three-year-old boy who had ataxic diplegia, mental retardation, horizontal pendular nystagmus with head nodding and abnormal auditory brain stem responses showing only waves I and II was presented. His clinical features coincided with recent reports in the Japanese literature of cases of a new syndrome that is congenital in origin and seen only in boys. PMID:3826555

  10. Clinical manifestations that predict abnormal brain computed tomography (CT) in children with minor head injury

    PubMed Central

    Alharthy, Nesrin; Al Queflie, Sulaiman; Alyousef, Khalid; Yunus, Faisel

    2015-01-01

    Background: Computed tomography (CT) used in pediatric pediatrics brain injury (TBI) to ascertain neurological manifestations. Nevertheless, this practice is associated with adverse effects. Reports in the literature suggest incidents of morbidity and mortality in children due to exposure to radiation. Hence, it is found imperative to search for a reliable alternative. Objectives: The aim of this study is to find a reliable clinical alternative to detect an intracranial injury without resorting to the CT. Materials and Methods: Retrospective cross-sectional study was undertaken in patients (1-14 years) with blunt head injury and having a Glasgow Coma Scale (GCS) of 13-15 who had CT performed on them. Using statistical analysis, the correlation between clinical examination and positive CT manifestation is analyzed for different age-groups and various mechanisms of injury. Results: No statistically significant association between parameteres such as Loss of Consciousness, ‘fall’ as mechanism of injury, motor vehicle accidents (MVA), more than two discrete episodes of vomiting and the CT finding of intracranial injury could be noted. Analyzed data have led to believe that GCS of 13 at presentation is the only important clinical predictor of intracranial injury. Conclusion: Retrospective data, small sample size and limited number of factors for assessing clinical manifestation might present constraints on the predictive rule that was derived from this review. Such limitations notwithstanding, the decision to determine which patients should undergo neuroimaging is encouraged to be based on clinical judgments. Further analysis with higher sample sizes may be required to authenticate and validate findings. PMID:25949038