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Sample records for specific brain functions

  1. Human brain networks function in connectome-specific harmonic waves.

    PubMed

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-01

    A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In this new frequency-specific representation of cortical activity, that we call 'connectome harmonics', oscillatory networks of the human brain at rest match harmonic wave patterns of certain frequencies. We demonstrate a neural mechanism behind the self-organization of connectome harmonics with a continuous neural field model of excitatory-inhibitory interactions on the connectome. Remarkably, the critical relation between the neural field patterns and the delicate excitation-inhibition balance fits the neurophysiological changes observed during the loss and recovery of consciousness. PMID:26792267

  2. Human brain networks function in connectome-specific harmonic waves

    PubMed Central

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-01

    A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In this new frequency-specific representation of cortical activity, that we call ‘connectome harmonics', oscillatory networks of the human brain at rest match harmonic wave patterns of certain frequencies. We demonstrate a neural mechanism behind the self-organization of connectome harmonics with a continuous neural field model of excitatory–inhibitory interactions on the connectome. Remarkably, the critical relation between the neural field patterns and the delicate excitation–inhibition balance fits the neurophysiological changes observed during the loss and recovery of consciousness. PMID:26792267

  3. Task-Specific Functional Brain Geometry from Model Maps

    PubMed Central

    Langs, Georg; Samaras, Dimitris; Paragios, Nikos; Honorio, Jean; Alia-Klein, Nelly; Tomasi, Dardo; Volkow, Nora D.; Goldstein, Rita Z.

    2016-01-01

    In this paper we propose model maps to derive and represent the intrinsic functional geometry of a brain from functional magnetic resonance imaging (fMRI) data for a specific task. Model maps represent the coherence of behavior of individual fMRI-measurements for a set of observations, or a time sequence. The maps establish a relation between individual positions in the brain by encoding the blood oxygen level dependent (BOLD) signal over a time period in a Markov chain. They represent this relation by mapping spatial positions to a new metric space, the model map. In this map the Euclidean distance between two points relates to the joint modeling behavior of their signals and thus the co-dependencies of the corresponding signals. The map reflects the functional as opposed to the anatomical geometry of the brain. It provides a quantitative tool to explore and study global and local patterns of resource allocation in the brain. To demonstrate the merit of this representation, we report quantitative experimental results on 29 fMRI time sequences, each with sub-sequences corresponding to 4 different conditions for two groups of individuals. We demonstrate that drug abusers exhibit lower differentiation in brain interactivity between baseline and reward related tasks, which could not be quantified until now. PMID:18979834

  4. 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…

  5. Electro-acupuncture at different acupoints modulating the relative specific brain functional network

    NASA Astrophysics Data System (ADS)

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

    2010-11-01

    Objective: The specific brain effects of acupoint are important scientific concern in acupuncture. However, previous acupuncture fMRI studies focused on acupoints in muscle layer on the limb. Therefore, researches on acupoints within connective tissue at trunk are warranted. Material and Methods: Brain effects of acupuncture on abdomen at acupoints Guanyuan (CV4) and Zhongwan (CV12) were tested using fMRI on 21 healthy volunteers. The data acquisition was performed at resting state, during needle retention, electroacupuncture (EA) and post-EA resting state. Needling sensations were rated after every electroacupuncture (EA) procedure. The needling sensations and the brain functional activity and connectivity were compared between CV4 and CV12 using SPSS, SPM2 and the local and remote connectivity maps. Results and conclusion: EA at CV4 and CV12 induced apparent deactivation effects in the limbic-paralimbic-neocortical network. The default mode of the brain was modified by needle retention and EA, respectively. The functional brain network was significantly changed post EA. However, the minor differences existed between these two acupoints. The results demonstrated similarity between functional brain network mode of acupuncture modulation and functional circuits of emotional and cognitive regulation. Acupuncture may produce analgesia, anti-anxiety and anti-depression via the limbic-paralimbic-neocortical network (LPNN).

  6. Functional specificity for high-level linguistic processing in the human brain

    PubMed Central

    Fedorenko, Evelina; Behr, Michael K.; Kanwisher, Nancy

    2011-01-01

    Neuroscientists have debated for centuries whether some regions of the human brain are selectively engaged in specific high-level mental functions or whether, instead, cognition is implemented in multifunctional brain regions. For the critical case of language, conflicting answers arise from the neuropsychological literature, which features striking dissociations between deficits in linguistic and nonlinguistic abilities, vs. the neuroimaging literature, which has argued for overlap between activations for linguistic and nonlinguistic processes, including arithmetic, domain general abilities like cognitive control, and music. Here, we use functional MRI to define classic language regions functionally in each subject individually and then examine the response of these regions to the nonlinguistic functions most commonly argued to engage these regions: arithmetic, working memory, cognitive control, and music. We find little or no response in language regions to these nonlinguistic functions. These data support a clear distinction between language and other cognitive processes, resolving the prior conflict between the neuropsychological and neuroimaging literatures. PMID:21885736

  7. Non-verbal emotion communication training induces specific changes in brain function and structure

    PubMed Central

    Kreifelts, Benjamin; Jacob, Heike; Brück, Carolin; Erb, Michael; Ethofer, Thomas; Wildgruber, Dirk

    2013-01-01

    The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure. PMID:24146641

  8. Frequency-specific Alterations of Large-scale Functional Brain Networks in Patients with Alzheimer's Disease

    PubMed Central

    Qin, Yuan-Yuan; Li, Ya-Peng; Zhang, Shun; Xiong, Ying; Guo, Lin-Ying; Yang, Shi-Qi; Yao, Yi-Hao; Li, Wei; Zhu, Wen-Zhen

    2015-01-01

    Background: Previous studies have indicated that the cognitive deficits in patients with Alzheimer's disease (AD) may be due to topological deteriorations of the brain network. However, whether the selection of a specific frequency band could impact the topological properties is still not clear. Our hypothesis is that the topological properties of AD patients are also frequency-specific. Methods: Resting state functional magnetic resonance imaging data from 10 right-handed moderate AD patients (mean age: 64.3 years; mean mini mental state examination [MMSE]: 18.0) and 10 age and gender-matched healthy controls (mean age: 63.6 years; mean MMSE: 28.2) were enrolled in this study. The global efficiency, the clustering coefficient (CC), the characteristic path length (CpL), and “small-world” property were calculated in a wide range of thresholds and averaged within each group, at three different frequency bands (0.01–0.06 Hz, 0.06–0.11 Hz, and 0.11–0.25 Hz). Results: At lower-frequency bands (0.01–0.06 Hz, 0.06–0.11 Hz), the global efficiency, the CC and the “small-world” properties of AD patients decreased compared to controls. While at higher-frequency bands (0.11–0.25 Hz), the CpL was much longer, and the “small-world” property was disrupted in AD, particularly at a higher threshold. The topological properties changed with different frequency bands, suggesting the existence of disrupted global and local functional organization associated with AD. Conclusions: This study demonstrates that the topological alterations of large-scale functional brain networks in AD patients are frequency dependent, thus providing fundamental support for optimal frequency selection in future related research. PMID:25698190

  9. Microglia Determine Brain Region-Specific Neurotoxic Responses to Chemically Functionalized Carbon Nanotubes.

    PubMed

    Bussy, Cyrill; Al-Jamal, Khuloud T; Boczkowski, Jorge; Lanone, Sophie; Prato, Maurizio; Bianco, Alberto; Kostarelos, Kostas

    2015-08-25

    Surface tunability and their ability to translocate plasma membranes make chemically functionalized carbon nanotubes (f-CNTs) promising intracellular delivery systems for therapeutic or diagnostic purposes in the central nervous system (CNS). The present study aimed to determine the biological impact of different types of multiwalled CNTs (MWNTs) on primary neuronal and glial cell populations isolated from fetal rat frontal cortex (FCO) and striatum (ST). Neurons from both brain regions were generally not affected by exposure to MWNTs as determined by a modified LDH assay. In contrast, the viability of mixed glia was reduced in ST-derived mixed glial cultures, but not in FCO-derived ones. Cytotoxicity was independent of MWNT type or dose, suggesting an inherent sensitivity to CNTs. Characterization of the cell populations in mixed glial cultures prior to nanotube exposure showed higher number of CD11b/c positive cells in the ST-derived mixed glial cultures. After exposure to MWNTs, CNT were uptaken more effectively by CD11b/c positive cells (microglia), compared to GFAP positive cells (astrocytes). When exposed to conditioned media from microglia enriched cultures exposed to MWNTs, ST-derived glial cultures secreted more NO than FCO-derived cells. These results suggested that the more significant cytotoxic response obtained from ST-derived mixed glia cultures was related to the higher number of microglial cells in this brain region. Our findings emphasize the role that resident macrophages of the CNS play in response to nanomaterials and the need to thoroughly investigate the brain region-specific effects toward designing implantable devices or delivery systems to the CNS. PMID:26043308

  10. GISP: a novel brain-specific protein that promotes surface expression and function of GABAB receptors

    PubMed Central

    Kantamneni, Sriharsha; Corrêa, Sônia A. L.; Hodgkinson, Gina K.; Meyer, Guido; Vinh, Ngoc Nga; Henley, Jeremy M.; Nishimune, Atsushi

    2012-01-01

    Synaptic transmission depends on the regulated surface expression of neurotransmitter receptors, but many of the cellular processes required to achieve this remain poorly understood. To better define specific mechanisms for the GABAB receptor (GABABR) trafficking, we screened for proteins that bind to the carboxy-terminus of the GABAB1 subunit. We report the identification and characterization of a novel 130-kDa protein, GPCR interacting scaffolding protein (GISP), that interacts directly with the GABAB1 subunit via a coiled-coil domain. GISP co-fractionates with GABABR and with the postsynaptic density and co-immunoprecipitates with GABAB1 and GABAB2 from rat brain. In cultured hippocampal neurons, GISP displays a punctate dendritic distribution and has an overlapping localization with GABABRs. When co-expressed with GABABRs in human embryonic kidney cells, GISP promotes GABABR surface expression and enhances both baclofen-evoked extracellular signal-regulated kinase (ERK) phosphorylation and G-protein inwardly rectifying potassium channel (GIRK) currents. These results suggest that GISP is involved in the forward trafficking and stabilization of functional GABABRs. PMID:17241134

  11. Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)

    ERIC Educational Resources Information Center

    de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

    2011-01-01

    Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

  12. Neurotransmitter Specific, Cellular-Resolution Functional Brain Mapping Using Receptor Coated Nanoparticles: Assessment of the Possibility

    PubMed Central

    Forati, Ebrahim; Sabouni, Abas; Ray, Supriyo; Head, Brian; Schoen, Christian; Sievenpiper, Dan

    2015-01-01

    Receptor coated resonant nanoparticles and quantum dots are proposed to provide a cellular-level resolution image of neural activities inside the brain. The functionalized nanoparticles and quantum dots in this approach will selectively bind to different neurotransmitters in the extra-synaptic regions of neurons. This allows us to detect neural activities in real time by monitoring the nanoparticles and quantum dots optically. Gold nanoparticles (GNPs) with two different geometries (sphere and rod) and quantum dots (QDs) with different sizes were studied along with three different neurotransmitters: dopamine, gamma-Aminobutyric acid (GABA), and glycine. The absorption/emission spectra of GNPs and QDs before and after binding of neurotransmitters and their corresponding receptors are reported. The results using QDs and nanorods with diameter 25nm and aspect rations larger than three were promising for the development of the proposed functional brain mapping approach. PMID:26717196

  13. Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

    PubMed

    Wang, Yi-Feng; Long, Zhiliang; Cui, Qian; Liu, Feng; Jing, Xiu-Juan; Chen, Heng; Guo, Xiao-Nan; Yan, Jin H; Chen, Hua-Fu

    2016-01-01

    Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (<1 Hz). However, it is difficult to determine the frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities. PMID:26512872

  14. Is the self a higher-order or fundamental function of the brain? The "basis model of self-specificity" and its encoding by the brain's spontaneous activity.

    PubMed

    Northoff, Georg

    2016-01-01

    What is the self? This is a question that has long been discussed in (Western) philosophy where the self is traditionally conceived a higher-order function at the apex or pinnacle of all functions. This tradition has been transferred to recent neuroscience where the self is often considered to be a higher-order cognitive function reflected in memory and other high-level judgements. However, other lines of research demonstrate a close and intimate relationship between self-specificity and more basic functions like perceptions, emotions and reward. This paper focuses on the relationship between self-specificity and other basic functions relating to emotions, reward and perception. I propose the basis model that conceives self-specificity as a fundamental feature of the brain's spontaneous activity. This is supported by recent findings showing rest-self overlap in midline regions as well as findings demonstrating that the resting state can predict subsequent degrees of self-specificity. I conclude that such self-specificity in the brain's spontaneous activity may be central in linking the self to either internal or external stimuli. This may also provide the basis for coding the self as subject in relation to internal (i.e., self-consciousness) or external (i.e., phenomenal consciousness) mental events. PMID:26505808

  15. Brain imaging and brain function

    SciTech Connect

    Sokoloff, L.

    1985-01-01

    This book is a survey of the applications of imaging studies of regional cerebral blood flow and metabolism to the investigation of neurological and psychiatric disorders. Contributors review imaging techniques and strategies for measuring regional cerebral blood flow and metabolism, for mapping functional neural systems, and for imaging normal brain functions. They then examine the applications of brain imaging techniques to the study of such neurological and psychiatric disorders as: cerebral ischemia; convulsive disorders; cerebral tumors; Huntington's disease; Alzheimer's disease; depression and other mood disorders. A state-of-the-art report on magnetic resonance imaging of the brain and central nervous system rounds out the book's coverage.

  16. Sex-Specific Patterns of Aberrant Brain Function in First-Episode Treatment-Naive Patients with Schizophrenia

    PubMed Central

    Lei, Wei; Li, Mingli; Deng, Wei; Zhou, Yi; Ma, Xiaohong; Wang, Qiang; Guo, Wanjun; Li, Yinfei; Jiang, Lijun; Han, Yuanyuan; Huang, Chaohua; Hu, Xun; Li, Tao

    2015-01-01

    Male and female patients with schizophrenia show significant differences in a number of important clinical features, yet the neural substrates of these differences are still poorly understood. Here we explored the sex differences in the brain functional aberrations in 124 treatment-naïve patients with first-episode schizophrenia (61 males), compared with 102 age-matched healthy controls (50 males). Maps of degree centrality (DC) and amplitude of low-frequency fluctuations (ALFF) were constructed using resting-state functional magnetic resonance imaging data and compared between groups. We found that: (1) Selective DC reduction was observed in the right putamen (Put_R) in male patients and the left middle frontal gyrus (MFG) in female patients; (2) Functional connectivity analysis (using Put_R and MFG as seeds) found that male and female patients have disturbed functional integration in two separate networks, i.e., the sensorimotor network and the default mode network; (3) Significant ALFF alterations were also observed in these two networks in both genders; (4) Sex specific brain functional alterations were associated with various symptoms in patients. These results suggested that sex-specific patterns of functional aberration existed in schizophrenia, and these patterns were associated with the clinical features both in male and female patients. PMID:26193256

  17. Specificity of Hemodynamic Brain Responses to Painful Stimuli: A functional near-infrared spectroscopy study

    PubMed Central

    Yücel, Meryem A.; Aasted, Christopher M.; Petkov, Mihayl P.; Borsook, David; Boas, David A.; Becerra, Lino

    2015-01-01

    Assessing pain in individuals not able to communicate (e.g. infants, under surgery, or following stroke) is difficult due to the lack of non-verbal objective measures of pain. Near-infrared spectroscopy (NIRS) being a portable, non-invasive and inexpensive method of monitoring cerebral hemodynamic activity has the potential to provide such a measure. Here we used functional NIRS to evaluate brain activation to an innocuous and a noxious electrical stimulus on healthy human subjects (n = 11). For both innocuous and noxious stimuli, we observed a signal change in the primary somatosensory cortex contralateral to the stimulus. The painful and non-painful stimuli can be differentiated based on their signal size and profile. We also observed that repetitive noxious stimuli resulted in adaptation of the signal. Furthermore, the signal was distinguishable from a skin sympathetic response to pain that tended to mask it. Our results support the notion that functional NIRS has a potential utility as an objective measure of pain. PMID:25820289

  18. Blockade of the brachial plexus abolishes activation of specific brain regions by electroacupuncture at LI4: a functional MRI study

    PubMed Central

    Gu, Weidong; Jiang, Wei; He, Jingwei; Liu, Songbin; Wang, Zhaoxin

    2015-01-01

    Objective Our aim was to test the hypothesis that electroacupuncture (EA) at acupuncture point LI4 activates specific brain regions by nerve stimulation that is mediatied through a pathway involving the brachial plexus. Methods Twelve acupuncture naive right-handed volunteers were allocated to receive three sessions of EA at LI4 in a random different order (crossover): (1) EA alone (EA); EA after injection of local anaesthetics into the deltoid muscle (EA+LA); and (3) EA after blockade of the brachial plexus (EA+NB). During each session, participants were imaged in a 3 T MRI scanner. Brain regions showing change in blood oxygen level-dependent (BOLD) signal (activation) were identified. Subjective acupuncture sensation was quantified after functional MRI scanning was completed. Results were compared between the three sessions for each individual, and averaged. Results Blockade of the brachial plexus inhibited acupuncture sensation during EA. EA and EA+LA activated the bilateral thalamus, basal ganglia, cerebellum and left putamen, whilst no significant activation was observed during EA+NB. The BOLD signal of the thalamus correlated significantly with acupuncture sensation score during EA. Conclusions Blockade of the brachial plexus completely abolishes patterns of brain activation induced by EA at LI4. The results suggest that EA activates specific brain regions through stimulation of the local nerves supplying the tissues at LI4, which transmit sensory information via the brachial plexus. Trial registration number ChiCTR-OO-13003389. PMID:26464415

  19. Differences in mitochondrial function in homogenated samples from healthy and epileptic specific brain tissues revealed by high-resolution respirometry.

    PubMed

    Burtscher, Johannes; Zangrandi, Luca; Schwarzer, Christoph; Gnaiger, Erich

    2015-11-01

    Mitochondrial dysfunction and oxidative stress are strongly implicated in neurodegenerative diseases and epilepsy. Strikingly, neurodegenerative diseases show regional specificity in vulnerability and follow distinct patterns of neuronal loss. A challenge is to understand, why mitochondria fail in particular brain regions under specific pathological conditions. A potential explanation could be provided by regional or cellular specificity of mitochondrial function. We applied high-resolution respirometry to analyze the integrated Complex I- and II (CI and CII)-linked respiration, the activity of Complex IV, and the combined CI&II-linked oxidative phosphorylation (OXPHOS)- and electron-transfer system (ETS)-capacity in microsamples obtained from distinct regions of the mouse brain. We compared different approaches to assess mitochondrial density and suggest flux control ratios as a valid method to normalize respiration to mitochondrial density. This approach revealed significant differences of CI- and CII-linked OXPHOS capacity and coupling control between motor cortex, striatum, hippocampus and pons of naïve mice. CI-linked respiration was highest in motor cortex, while CII-linked respiration predominated in the striatum. To investigate if this method could also determine differences in normal and disease states within the same brain region, we compared hippocampal homogenates in a chronic epilepsy model. Three weeks after stereotaxic injection of kainate, there was a down-regulation of CI- and upregulation of CII-linked respiration in the resulting epileptic ipsilateral hippocampus compared to the contralateral one. In summary, respirometric OXPHOS analysis provides a very sensitive diagnostic approach using small amounts of distinct brain tissues. In a single assay, information is obtained on numerous OXPHOS parameters as indicators of tissue-specific mitochondrial performance. PMID:26516105

  20. Split Brain Functioning.

    ERIC Educational Resources Information Center

    Cassel, Russell N.

    1978-01-01

    Summarizing recent research, this article defines the functions performed by the left and right sides of the human brain. Attention is given to the right side, or the nondominant side, of the brain and its potential in terms of perception of the environment, music, art, geometry, and the aesthetics. (JC)

  1. COPPER AND BRAIN FUNCTION

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing evidence shows that brain development and function are impaired when the brain is deprived of copper either through dietary copper deficiency or through genetic defects in copper transport. A number of copper-dependent enzymes whose activities are lowered by copper deprivation form the ba...

  2. Lutein and Brain Function

    PubMed Central

    Erdman, John W.; Smith, Joshua W.; Kuchan, Matthew J.; Mohn, Emily S.; Johnson, Elizabeth J.; Rubakhin, Stanislav S.; Wang, Lin; Sweedler, Jonathan V.; Neuringer, Martha

    2015-01-01

    Lutein is one of the most prevalent carotenoids in nature and in the human diet. Together with zeaxanthin, it is highly concentrated as macular pigment in the foveal retina of primates, attenuating blue light exposure, providing protection from photo-oxidation and enhancing visual performance. Recently, interest in lutein has expanded beyond the retina to its possible contributions to brain development and function. Only primates accumulate lutein within the brain, but little is known about its distribution or physiological role. Our team has begun to utilize the rhesus macaque (Macaca mulatta) model to study the uptake and bio-localization of lutein in the brain. Our overall goal has been to assess the association of lutein localization with brain function. In this review, we will first cover the evolution of the non-human primate model for lutein and brain studies, discuss prior association studies of lutein with retina and brain function, and review approaches that can be used to localize brain lutein. We also describe our approach to the biosynthesis of 13C-lutein, which will allow investigation of lutein flux, localization, metabolism and pharmacokinetics. Lastly, we describe potential future research opportunities. PMID:26566524

  3. Brain Dynamics Promotes Function

    NASA Astrophysics Data System (ADS)

    Lourenço, Carlos

    Dynamical structure in the brain promotes biological function. Natural scientists look for correlations between measured electrical signals and behavior or mental states. Computational scientists have new opportunities to receive ’algorithmic’ inspiration from brain processes and propose computational paradigms. Thus a tradition which dates back to the 1940s with neural nets research is renewed. Real processes in the brain are ’complex’ and withstand trivial descriptions. However, dynamical complexity need not be at odds with a computational description of the phenomena and with the inspiration for algorithms that actually compute something in an engineering sense. We engage this complexity from a computational viewpoint, not excluding dynamical regimes that a number of authors are willing to label as chaos. The key question is: what may we be missing computation-wise if we overlook brain dynamics? At this point in brain research, we are happy if we can at least provide a partial answer.

  4. Functional Brain Basis of Hypnotizability

    PubMed Central

    Hoeft, Fumiko; Gabrieli, John D.E.; Whitfield-Gabrieli, Susan; Haas, Brian W.; Bammer, Roland; Menon, Vinod; Spiegel, David

    2015-01-01

    Context Focused hypnotic concentration is a model for brain control over sensation and behavior. Pain and anxiety can be effectively alleviated by hypnotic suggestion, which modulates activity in brain regions associated with focused attention, but the specific neural network underlying this phenomenon is not known. Objective The main goal of the study was to investigate the brain basis of hypnotizability. Design Cross sectional, in-vivo neuroimaging study. Setting Academic medical center at Stanford University School of Medicine. Patients 12 adults with high and 12 adults with low hypnotizability. Main Outcome Measures (1) functional MRI (fMRI) to measure functional connectivity networks at rest including default-mode, salience and executive-control networks, (2) structural T1 MRI to measure regional grey and white matter volumes, and (3) diffusion tensor imaging (DTI) to measure white matter microstructural integrity. Results High-compared to low-hypnotizable individuals showed greater functional connectivity between left dorsolateral prefrontal cortex (DLPFC), an executive-control region of the brain, and the salience network composed of the dorsal anterior cingulate cortex (dACC), anterior insula, amygdala, and ventral striatum, involved in detecting, integrating, and filtering relevant somatic, autonomic, and emotional information, using independent component analysis (ICA). Seed based analysis confirmed elevated functional coupling between the dACC and the DLPFC in high, compared to low, hypnotizables. These functional differences were not due to variation in brain structure in these regions, including regional grey and white matter volumes and white matter microstructure. Conclusions Our results provide novel evidence that altered functional connectivity in DLPFC and dACC may underlie hypnotizability. Future studies focusing on how these functional networks change and interact during hypnosis are warranted. PMID:23026956

  5. Modulating brain oscillations to drive brain function.

    PubMed

    Thut, Gregor

    2014-12-01

    Do neuronal oscillations play a causal role in brain function? In a study in this issue of PLOS Biology, Helfrich and colleagues address this long-standing question by attempting to drive brain oscillations using transcranial electrical current stimulation. Remarkably, they were able to manipulate visual perception by forcing brain oscillations of the left and right visual hemispheres into synchrony using oscillatory currents over both hemispheres. Under this condition, human observers more often perceived an inherently ambiguous visual stimulus in one of its perceptual instantiations. These findings shed light on the mechanisms underlying neuronal computation. They show that it is the neuronal oscillations that drive the visual experience, not the experience driving the oscillations. And they indicate that synchronized oscillatory activity groups brain areas into functional networks. This points to new ways for controlled experimental and possibly also clinical interventions for the study and modulation of brain oscillations and associated functions. PMID:25549340

  6. Modulating Brain Oscillations to Drive Brain Function

    PubMed Central

    Thut, Gregor

    2014-01-01

    Do neuronal oscillations play a causal role in brain function? In a study in this issue of PLOS Biology, Helfrich and colleagues address this long-standing question by attempting to drive brain oscillations using transcranial electrical current stimulation. Remarkably, they were able to manipulate visual perception by forcing brain oscillations of the left and right visual hemispheres into synchrony using oscillatory currents over both hemispheres. Under this condition, human observers more often perceived an inherently ambiguous visual stimulus in one of its perceptual instantiations. These findings shed light on the mechanisms underlying neuronal computation. They show that it is the neuronal oscillations that drive the visual experience, not the experience driving the oscillations. And they indicate that synchronized oscillatory activity groups brain areas into functional networks. This points to new ways for controlled experimental and possibly also clinical interventions for the study and modulation of brain oscillations and associated functions. PMID:25549340

  7. Dynamic neuroimaging of brain function.

    PubMed

    Simpson, G V; Pflieger, M E; Foxe, J J; Ahlfors, S P; Vaughan, H G; Hrabe, J; Ilmoniemi, R J; Lantos, G

    1995-09-01

    To fully characterize the brain processes underlying sensorimotor and cognitive function, the spatial distribution of active regions, their interconnected regions must be measured. We describe methods for imaging brain sources from surface-recorded EEG and magnetoencephalographic data, called electromagnetic source imaging (EMSI). EMSI provides brain source locations within the common framework of magnetic resonance (MR) images of brain anatomy. This allows integration of data from other functional brain imaging methods, like positron emission tomography and functional MR imaging, which can improve the accuracy of EMSI localization. EMSI also provides submillisecond temporal resolution of the dynamic processes within brain systems. Examples are given of applications to visual perceptual and attentional studies. PMID:8576389

  8. High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression.

    PubMed

    Kuhlman, Sandra J; Huang, Z Josh

    2008-01-01

    We describe a method that combines Cre-recombinase knockin mice and viral-mediated gene transfer to genetically label and functionally manipulate specific neuron types in the mouse brain. We engineered adeno-associated viruses (AAVs) that express GFP, dsRedExpress, or channelrhodopsin (ChR2) upon Cre/loxP recombination-mediated removal of a transcription-translation STOP cassette. Fluorescent labeling was sufficient to visualize neuronal structures with synaptic resolution in vivo, and ChR2 expression allowed light activation of neuronal spiking. The structural dynamics of a specific class of neocortical neuron, the parvalbumin-containing (Pv) fast-spiking GABAergic interneuron, was monitored over the course of a week. We found that although the majority of Pv axonal boutons were stable in young adults, bouton additions and subtractions on axonal shafts were readily observed at a rate of 10.10% and 9.47%, respectively, over 7 days. Our results indicate that Pv inhibitory circuits maintain the potential for structural re-wiring in post-adolescent cortex. With the generation of an increasing number of Cre knockin mice and because viral transfection can be delivered to defined brain regions at defined developmental stages, this strategy represents a general method to systematically visualize the structure and manipulate the function of different cell types in the mouse brain. PMID:18414675

  9. High-Resolution Labeling and Functional Manipulation of Specific Neuron Types in Mouse Brain by Cre-Activated Viral Gene Expression

    PubMed Central

    Kuhlman, Sandra J.; Huang, Z. Josh

    2008-01-01

    We describe a method that combines Cre-recombinase knockin mice and viral-mediated gene transfer to genetically label and functionally manipulate specific neuron types in the mouse brain. We engineered adeno-associated viruses (AAVs) that express GFP, dsRedExpress, or channelrhodopsin (ChR2) upon Cre/loxP recombination-mediated removal of a transcription-translation STOP cassette. Fluorescent labeling was sufficient to visualize neuronal structures with synaptic resolution in vivo, and ChR2 expression allowed light activation of neuronal spiking. The structural dynamics of a specific class of neocortical neuron, the parvalbumin-containing (Pv) fast-spiking GABAergic interneuron, was monitored over the course of a week. We found that although the majority of Pv axonal boutons were stable in young adults, bouton additions and subtractions on axonal shafts were readily observed at a rate of 10.10% and 9.47%, respectively, over 7 days. Our results indicate that Pv inhibitory circuits maintain the potential for structural re-wiring in post-adolescent cortex. With the generation of an increasing number of Cre knockin mice and because viral transfection can be delivered to defined brain regions at defined developmental stages, this strategy represents a general method to systematically visualize the structure and manipulate the function of different cell types in the mouse brain. PMID:18414675

  10. Evaluation of the Contribution of Signals Originating from Large Blood Vessels to Signals of Functionally Specific Brain Areas

    PubMed Central

    Chung, Jun-Young; Sung, Yul-Wan; Ogawa, Seiji

    2015-01-01

    The fusiform face area (FFA) is known to play a pivotal role in face processing. The FFA is located in the ventral region, at the base of the brain, through which large blood vessels run. The location of the FFA via functional MRI (fMRI) may be influenced by these large blood vessels. Responses of large blood vessels may not exactly correspond to neuronal activity in a target area, because they may be diluted and influenced by inflow effects. In this study, we investigated the effects of large blood vessels in the FFA, that is, whether the FFA includes large blood vessels and/or whether inflow signals contribute to fMRI signals of the FFA. For this purpose, we used susceptibility-weighted imaging (SWI) sequences to visualize large blood vessels and dual-echo gradient-echo echo-planar imaging (GE-EPI) to measure inflow effects. These results showed that the location and response signals of the FFA were not influenced by large blood vessels or inflow effects, although large blood vessels were located near the FFA. Therefore, the data from the FFA obtained by individual analysis were robust to large blood vessels but leaving a warning that the data obtained by group analysis may be prone to large blood vessels. PMID:26413511

  11. Evaluation of the Contribution of Signals Originating from Large Blood Vessels to Signals of Functionally Specific Brain Areas.

    PubMed

    Chung, Jun-Young; Sung, Yul-Wan; Ogawa, Seiji

    2015-01-01

    The fusiform face area (FFA) is known to play a pivotal role in face processing. The FFA is located in the ventral region, at the base of the brain, through which large blood vessels run. The location of the FFA via functional MRI (fMRI) may be influenced by these large blood vessels. Responses of large blood vessels may not exactly correspond to neuronal activity in a target area, because they may be diluted and influenced by inflow effects. In this study, we investigated the effects of large blood vessels in the FFA, that is, whether the FFA includes large blood vessels and/or whether inflow signals contribute to fMRI signals of the FFA. For this purpose, we used susceptibility-weighted imaging (SWI) sequences to visualize large blood vessels and dual-echo gradient-echo echo-planar imaging (GE-EPI) to measure inflow effects. These results showed that the location and response signals of the FFA were not influenced by large blood vessels or inflow effects, although large blood vessels were located near the FFA. Therefore, the data from the FFA obtained by individual analysis were robust to large blood vessels but leaving a warning that the data obtained by group analysis may be prone to large blood vessels. PMID:26413511

  12. Dynamic imaging of brain function

    PubMed Central

    Hyder, Fahmeed

    2013-01-01

    In recent years, there have been unprecedented methodological advances in the dynamic imaging of brain activities. Electrophysiological, optical, and magnetic resonance methods now allow mapping of functional activation (or deactivation) by measurement of neuronal activity (e.g., membrane potential, ion flux, neurotransmitter flux), energy metabolism (e.g., glucose consumption, oxygen consumption, creatine kinase flux), and functional hyperemia (e.g., blood oxygenation, blood flow, blood volume). Properties of the glutamatergic synapse are used as a model to reveal activities at the nerve terminal and their associated changes in energy demand and blood flow. This approach reveals that each method measures different tissue- and/or cell-specific components with specified spatiotemporal resolution. While advantages and disadvantages of different methods are apparent and often used to supersede one another in terms of specificity and/or sensitivity, no particular technique is the optimal dynamic brain imaging method because each method is unique in some respect. Because the demand for energy substrates is a fundamental requirement for function, energy-based methods may allow quantitative dynamic imaging in vivo. However there are exclusive neurobiological insights gained by combining some of these different dynamic imaging techniques. PMID:18839085

  13. BEND3 is involved in the human-specific repression of calreticulin: Implication for the evolution of higher brain functions in human.

    PubMed

    Aghajanirefah, A; Nguyen, L N; Ohadi, M

    2016-01-15

    Recent emerging evidence indicates that changes in gene expression levels are linked to human evolution. We have previously reported a human-specific nucleotide in the promoter sequence of the calreticulin (CALR) gene at position -220C, which is the site of action of valproic acid. Reversion of this nucleotide to the ancestral A-allele has been detected in patients with degrees of deficit in higher brain cognitive functions. This mutation has since been reported in the 1000 genomes database at an approximate frequency of <0.0004 in humans (rs138452745). In the study reported here, we present update on the status of rs138452745 across evolution, based on the Ensembl and NCBI databases. The DNA pulldown assay was also used to identify the proteins binding to the C- and A-alleles, using two cell lines, SK-N-BE and HeLa. Consistent with our previous findings, the C-allele is human-specific, and the A-allele is the rule across all other species (N=38). This nucleotide resides in a block of 12-nucleotides that is strictly conserved across evolution. The DNA pulldown experiments revealed that in both SK-N-BE and HeLa cells, the transcription repressor BEN domain containing 3 (BEND3) binds to the human-specific C-allele, whereas the nuclear factor I (NFI) family members, NF1A, B, C, and X, specifically bind to the ancestral A-allele. This binding pattern is consistent with a previously reported decreased promoter activity of the C-allele vs. the A-allele. We propose that there is a link between binding of BEND3 to the CALR rs138452745 C-allele and removal of NFI binding site from this nucleotide, and the evolution of human-specific higher brain functions. To our knowledge, CALR rs138452745 is the first instance of enormous nucleotide conservation across evolution, except in the human species. PMID:26481236

  14. The brain timewise: how timing shapes and supports brain function

    PubMed Central

    Hari, Riitta; Parkkonen, Lauri

    2015-01-01

    We discuss the importance of timing in brain function: how temporal dynamics of the world has left its traces in the brain during evolution and how we can monitor the dynamics of the human brain with non-invasive measurements. Accurate timing is important for the interplay of neurons, neuronal circuitries, brain areas and human individuals. In the human brain, multiple temporal integration windows are hierarchically organized, with temporal scales ranging from microseconds to tens and hundreds of milliseconds for perceptual, motor and cognitive functions, and up to minutes, hours and even months for hormonal and mood changes. Accurate timing is impaired in several brain diseases. From the current repertoire of non-invasive brain imaging methods, only magnetoencephalography (MEG) and scalp electroencephalography (EEG) provide millisecond time-resolution; our focus in this paper is on MEG. Since the introduction of high-density whole-scalp MEG/EEG coverage in the 1990s, the instrumentation has not changed drastically; yet, novel data analyses are advancing the field rapidly by shifting the focus from the mere pinpointing of activity hotspots to seeking stimulus- or task-specific information and to characterizing functional networks. During the next decades, we can expect increased spatial resolution and accuracy of the time-resolved brain imaging and better understanding of brain function, especially its temporal constraints, with the development of novel instrumentation and finer-grained, physiologically inspired generative models of local and network activity. Merging both spatial and temporal information with increasing accuracy and carrying out recordings in naturalistic conditions, including social interaction, will bring much new information about human brain function. PMID:25823867

  15. Brain foods: the effects of nutrients on brain function

    PubMed Central

    Gómez-Pinilla, Fernando

    2009-01-01

    It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators of synaptic plasticity, such as brain-derived neurotrophic factor, can function as metabolic modulators, responding to peripheral signals such as food intake. Understanding the molecular basis of the effects of food on cognition will help us to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness. PMID:18568016

  16. Magnetic Resonance, Functional (fMRI) -- Brain

    MedlinePlus

    ... thought, speech, movement and sensation, which is called brain mapping. help assess the effects of stroke, trauma or degenerative disease (such as Alzheimer's) on brain function. monitor the growth and function of brain ...

  17. Modeling of region-specific fMRI BOLD neurovascular response functions in rat brain reveals residual differences that correlate with the differences in regional evoked potentials.

    PubMed

    Pawela, Christopher P; Hudetz, Anthony G; Ward, B Douglas; Schulte, Marie L; Li, Rupeng; Kao, Dennis S; Mauck, Matthew C; Cho, Younghoon R; Neitz, Jay; Hyde, James S

    2008-06-01

    The response of the rat visual system to flashes of blue light has been studied by blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The BOLD temporal response is dependent on the number of flashes presented and demonstrates a refractory period that depends on flash frequency. Activated brain regions included the primary and secondary visual cortex, superior colliculus (SC), dorsal lateral geniculate (DLG), and lateral posterior nucleus (LP), which were found to exhibit differing temporal responses. To explain these differences, the BOLD neurovascular response function was modeled. A second-order differential equation was developed and solved numerically to arrive at region-specific response functions. Included in the model are the light input from the diode (duty cycle), a refractory period, a transient response following onset and cessation of stimulus, and a slow adjustment to changes in the average level of the signal. Constants in the differential equation were evaluated for each region by fitting the model to the experimental BOLD response from a single flash, and the equation was then solved for multiple flashes. The simulation mimics the major features of the data; however, remaining differences in the frequency dependence of the response between the cortical and subcortical regions were unexplained. We hypothesized that these discrepancies were due to regional-specific differences in neuronal response to flash frequency. To test this hypothesis, cortical visual evoked potentials (VEPs) were recorded using the same stimulation protocol as the fMRI. Cortical VEPs were more suppressed than subcortical VEPs as flash frequency increased, supporting our hypothesis. This is the first report that regional differences in neuronal activation to the same stimulus lead to differential BOLD activation. PMID:18406628

  18. [Anesthetic mechanisms revealed by functional brain imaging].

    PubMed

    Kurata, Jiro

    2011-05-01

    Recent advancement in functional brain imaging techniques has revealed much of the global effects of general anesthetics on the human brain. General anesthetics preferentially suppress specific brain areas including the parietal association cortex and the thalamus, part of which appears to mirror the default mode network. Low-level sensory areas are relatively preserved and remain activated even under deep sedation by anesthetics. Functional connectivity analysis by resting-state functional magnetic resonance imaging has shown that general anesthetics moderately suppress functional connectivity of the default mode network. Midazolam-induced loss of consciousness is associated with remarkable suppression of cortico-cortical propagation of evoked currents. Overall, those results prompt us to hypothesize that general anesthetics induce loss of consciousness by disrupting the integrative properties of the cerebral cortex. PMID:21626860

  19. Natriuretic Hormones in Brain Function

    PubMed Central

    Hodes, Anastasia; Lichtstein, David

    2014-01-01

    Natriuretic hormones (NH) include three groups of compounds: the natriuretic peptides (ANP, BNP and CNP), the gastrointestinal peptides (guanylin and uroguanylin), and endogenous cardiac steroids. These substances induce the kidney to excrete sodium and therefore participate in the regulation of sodium and water homeostasis, blood volume, and blood pressure (BP). In addition to their peripheral functions, these hormones act as neurotransmitters or neuromodulators in the brain. In this review, the established information on the biosynthesis, release and function of NH is discussed, with particular focus on their role in brain function. The available literature on the expression patterns of each of the NH and their receptors in the brain is summarized, followed by the evidence for their roles in modulating brain function. Although numerous open questions exist regarding this issue, the available data support the notion that NH participate in the central regulation of BP, neuroprotection, satiety, and various psychiatric conditions, including anxiety, addiction, and depressive disorders. In addition, the interactions between the different NH in the periphery and the brain are discussed. PMID:25506340

  20. Prospects for Optogenetic Augmentation of Brain Function.

    PubMed

    Jarvis, Sarah; Schultz, Simon R

    2015-01-01

    The ability to optically control neural activity opens up possibilities for the restoration of normal function following neurological disorders. The temporal precision, spatial resolution, and neuronal specificity that optogenetics offers is unequalled by other available methods, so will it be suitable for not only restoring but also extending brain function? As the first demonstrations of optically "implanted" novel memories emerge, we examine the suitability of optogenetics as a technique for extending neural function. While optogenetics is an effective tool for altering neural activity, the largest impediment for optogenetics in neural augmentation is our systems level understanding of brain function. Furthermore, a number of clinical limitations currently remain as substantial hurdles for the applications proposed. While neurotechnologies for treating brain disorders and interfacing with prosthetics have advanced rapidly in the past few years, partially addressing some of these critical problems, optogenetics is not yet suitable for use in humans. Instead we conclude that for the immediate future, optogenetics is the neurological equivalent of the 3D printer: its flexibility providing an ideal tool for testing and prototyping solutions for treating brain disorders and augmenting brain function. PMID:26635547

  1. Prospects for Optogenetic Augmentation of Brain Function

    PubMed Central

    Jarvis, Sarah; Schultz, Simon R.

    2015-01-01

    The ability to optically control neural activity opens up possibilities for the restoration of normal function following neurological disorders. The temporal precision, spatial resolution, and neuronal specificity that optogenetics offers is unequalled by other available methods, so will it be suitable for not only restoring but also extending brain function? As the first demonstrations of optically “implanted” novel memories emerge, we examine the suitability of optogenetics as a technique for extending neural function. While optogenetics is an effective tool for altering neural activity, the largest impediment for optogenetics in neural augmentation is our systems level understanding of brain function. Furthermore, a number of clinical limitations currently remain as substantial hurdles for the applications proposed. While neurotechnologies for treating brain disorders and interfacing with prosthetics have advanced rapidly in the past few years, partially addressing some of these critical problems, optogenetics is not yet suitable for use in humans. Instead we conclude that for the immediate future, optogenetics is the neurological equivalent of the 3D printer: its flexibility providing an ideal tool for testing and prototyping solutions for treating brain disorders and augmenting brain function. PMID:26635547

  2. Advantages in functional imaging of the brain

    PubMed Central

    Mier, Walter; Mier, Daniela

    2015-01-01

    As neuronal pathologies cause only minor morphological alterations, molecular imaging techniques are a prerequisite for the study of diseases of the brain. The development of molecular probes that specifically bind biochemical markers and the advances of instrumentation have revolutionized the possibilities to gain insight into the human brain organization and beyond this—visualize structure-function and brain-behavior relationships. The review describes the development and current applications of functional brain imaging techniques with a focus on applications in psychiatry. A historical overview of the development of functional imaging is followed by the portrayal of the principles and applications of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), two key molecular imaging techniques that have revolutionized the ability to image molecular processes in the brain. We conclude that the juxtaposition of PET and fMRI in hybrid PET/MRI scanners enhances the significance of both modalities for research in neurology and psychiatry and might pave the way for a new area of personalized medicine. PMID:26042013

  3. [Brain function and white matter].

    PubMed

    Wake, Hiroaki; Kato, Daisuke

    2015-04-01

    Accumulated evidence shows that neural information processing takes place in superficial layers of the brain called the gray matter. Synapses, which connect different neurons reside in the gray matter and are considered the major components of information processing and plasticity. On the other hand, myelinated axons lie beneath the gray matter. These bundles of cables connect neurons in the different brain regions to form functional neural circuits. Myelinated axons were of little of interest to neuroscientists and have long been ignored in the formation of functional neuronal circuits. Recent evidence shows that myelin formed by oligodendrocytes shows plastic changes depending on neuronal activity. In this issue, we discuss the plastic changes of myelin and its functional role in learning and training. PMID:25846599

  4. A Point Mutation in Translation Initiation Factor eIF2B Leads to Function- and Time-Specific Changes in Brain Gene Expression

    PubMed Central

    Marom, Liraz; Ulitsky, Igor; Cabilly, Yuval; Shamir, Ron; Elroy-Stein, Orna

    2011-01-01

    Background Mutations in eukaryotic translation initiation factor 2B (eIF2B) cause Childhood Ataxia with CNS Hypomyelination (CACH), also known as Vanishing White Matter disease (VWM), which is associated with a clinical pathology of brain myelin loss upon physiological stress. eIF2B is the guanine nucleotide exchange factor (GEF) of eIF2, which delivers the initiator tRNAMet to the ribosome. We recently reported that a R132H mutation in the catalytic subunit of this GEF, causing a 20% reduction in its activity, leads under normal conditions to delayed brain development in a mouse model for CACH/VWM. To further explore the effect of the mutation on global gene expression in the brain, we conducted a wide-scale transcriptome analysis of the first three critical postnatal weeks. Methodology/Principal Findings Genome-wide mRNA expression of wild-type and mutant mice was profiled at postnatal (P) days 1, 18 and 21 to reflect the early proliferative stage prior to white matter establishment (P1) and the peak of oligodendrocye differentiation and myelin synthesis (P18 and P21). At each developmental stage, between 441 and 818 genes were differentially expressed in the mutant brain with minimal overlap, generating unique time point-specific gene expression signatures. Conclusions The current study demonstrates that a point mutation in eIF2B, a key translation initiation factor, has a massive effect on global gene expression in the brain. The overall changes in expression patterns reflect multiple layers of indirect effects that accumulate as the brain develops and matures. The differentially expressed genes seem to reflect delayed waves of gene expression as well as an adaptation process to cope with hypersensitivity to cellular stress. PMID:22073122

  5. [Localization of language function in the brain].

    PubMed

    Miyashita, Hiroyuki; Sakai, Kuniyoshi L

    2011-12-01

    Since the first report of an aphasic patient by Paul Broca, the localization of brain function has been disputed for 150 years. In lesion studies, double dissociation has been a key concept to show the localization of particular cognitive functions. The advancement of non-invasive brain imaging methods enables us to investigate the brain activities under well-controlled conditions, further promoting the studies on the localization of the cognitive functions, including language function. Brain imaging studies, together with subtraction and correlation analyses, have accumulated evidence that syntax, phonology, and sentence comprehension are separately processed by modules in different cortical regions. More specifically, it has been clarified that the module for syntax localizes in the left lateral premotor cortex and the opercular/triangular parts of the left inferior frontal gyrus. This modular structure further suggests that aphasia is interpreted as deficits in either syntactic or phonological processing. Therefore, the classical model of contrasting speech production and comprehension should be updated. According to theoretical linguistics, on the other hand, the recursive computation of syntactic structures is an essential feature of human language faculty. One direction of research would be to contrast human beings and animals for the abilities of processing symbolic sequences. Another direction is to clarify that the human brain is indeed specialized in language processing, which can be revealed by well-controlled language tasks and functional imaging techniques. Here we will review recent studies that demonstrate the existence of grammar center in the left frontal cortex. The future studies in the neuroscience of language will eventually elucidate the cortical localization of language function in a more precise way, i.e., what is really computed in the human brain. PMID:22147453

  6. Specific Binding of Atrial Natriuretic Factor in Brain Microvessels

    NASA Astrophysics Data System (ADS)

    Chabrier, Pierre E.; Roubert, Pierre; Braquet, Pierre

    1987-04-01

    Cerebral capillaries constitute the blood--brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. We examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using 125I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity (dissociation constant, ≈ 10-10 M) and with a binding capacity of 58 fmol/mg of protein. The binding of 125I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood--brain barrier function.

  7. Specific binding of atrial natriuretic factor in brain microvessels

    SciTech Connect

    Chabrier, P.E.; Roubert, P.; Braquet, P.

    1987-04-01

    Cerebral capillaries constitute the blood-brain barrier. Studies of specific receptors (neurotransmitters or hormones) located on this structure can be performed by means of radioligand-binding techniques on isolated brain microvessels. The authors examined on pure bovine cerebral microvessel preparations the binding of atrial natriuretic factor (ANF), using /sup 125/I-labeled ANF. Saturation and competition experiments demonstrated the presence of a single class of ANF-binding sites with high affinity and with a binding capacity of 58 fmol/mg of protein. The binding of /sup 125/I-labeled ANF to brain microvessels is specific, reversible, and time dependent, as is shown by association-dissociation experiments. The demonstration of specific ANF-binding sites on brain microvessels supposes a physiological role of ANF on brain microvasculature. The coexistence of ANF and angiotensin II receptors on this cerebrovascular tissue suggests that the two circulating peptides may act as mutual antagonists in the regulation of brain microcirculation and/or blood-brain barrier function.

  8. Differentiating cognitive functions of poststroke patients with specific brain lesions: A preliminary study on the clinical utility of Cognistat-P.

    PubMed

    Chan, Sam C C; Chan, Chetwyn C H; Wu, Yi; Liu, Karen P Y; Xu, Yan-Wen

    2016-01-01

    The Cognistat is widely used to measure the cognitive profile of neurological patients. This study aimed to further obtain evidence on the construct and discriminative validity of the Putonghua version of the Cognistat (Cognistat-P) on poststroke patients with specific brain lesions. Cognistat-P was administered to poststroke patients (n = 98), as well as healthy elderly (n = 40) and adult (n = 34) participants as the control groups. Poststroke patients were further categorized into 4 lesion groups using standard brain slice templates. Exploratory factory analysis reflected a 2-factor structure for the Cognistat-P that resembles that for the original English version. The Construction, Similarities, and Judgment subtests were found to differentiate patients with frontal or parietal lesions from those with subcortical lesions (p < .01, R(2) = .48). The Construction subtest, tapping the "fluid" ability, was the most useful for differentiating patients with parietal lesions from those with subcortical lesions. The Similarities subtest together with the Construction subtest was the most useful for differentiating patients with frontal lesions from those with subcortical lesions. This study established the validity of the Cognistat-P for differentiating poststroke patients with specific brain lesions. Future studies should replicate the results on a larger sample size and test the clinical significance of the Cognistat-P profiles. PMID:26571130

  9. DHA Effects in Brain Development and Function.

    PubMed

    Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B S; Ciappolino, Valentina; Agostoni, Carlo

    2016-01-01

    Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders. PMID:26742060

  10. DHA Effects in Brain Development and Function

    PubMed Central

    Lauritzen, Lotte; Brambilla, Paolo; Mazzocchi, Alessandra; Harsløf, Laurine B. S.; Ciappolino, Valentina; Agostoni, Carlo

    2016-01-01

    Docosahexaenoic acid (DHA) is a structural constituent of membranes specifically in the central nervous system. Its accumulation in the fetal brain takes place mainly during the last trimester of pregnancy and continues at very high rates up to the end of the second year of life. Since the endogenous formation of DHA seems to be relatively low, DHA intake may contribute to optimal conditions for brain development. We performed a narrative review on research on the associations between DHA levels and brain development and function throughout the lifespan. Data from cell and animal studies justify the indication of DHA in relation to brain function for neuronal cell growth and differentiation as well as in relation to neuronal signaling. Most data from human studies concern the contribution of DHA to optimal visual acuity development. Accumulating data indicate that DHA may have effects on the brain in infancy, and recent studies indicate that the effect of DHA may depend on gender and genotype of genes involved in the endogenous synthesis of DHA. While DHA levels may affect early development, potential effects are also increasingly recognized during childhood and adult life, suggesting a role of DHA in cognitive decline and in relation to major psychiatric disorders. PMID:26742060

  11. Peroxisomes in brain development and function.

    PubMed

    Berger, Johannes; Dorninger, Fabian; Forss-Petter, Sonja; Kunze, Markus

    2016-05-01

    Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer's disease, autism and amyotrophic lateral sclerosis. This article is part of a Special Issue entitled: Peroxisomes edited by Ralf Erdmann. PMID:26686055

  12. Robust transient dynamics and brain functions.

    PubMed

    Rabinovich, Mikhail I; Varona, Pablo

    2011-01-01

    In the last few decades several concepts of dynamical systems theory (DST) have guided psychologists, cognitive scientists, and neuroscientists to rethink about sensory motor behavior and embodied cognition. A critical step in the progress of DST application to the brain (supported by modern methods of brain imaging and multi-electrode recording techniques) has been the transfer of its initial success in motor behavior to mental function, i.e., perception, emotion, and cognition. Open questions from research in genetics, ecology, brain sciences, etc., have changed DST itself and lead to the discovery of a new dynamical phenomenon, i.e., reproducible and robust transients that are at the same time sensitive to informational signals. The goal of this review is to describe a new mathematical framework - heteroclinic sequential dynamics - to understand self-organized activity in the brain that can explain certain aspects of robust itinerant behavior. Specifically, we discuss a hierarchy of coarse-grain models of mental dynamics in the form of kinetic equations of modes. These modes compete for resources at three levels: (i) within the same modality, (ii) among different modalities from the same family (like perception), and (iii) among modalities from different families (like emotion and cognition). The analysis of the conditions for robustness, i.e., the structural stability of transient (sequential) dynamics, give us the possibility to explain phenomena like the finite capacity of our sequential working memory - a vital cognitive function -, and to find specific dynamical signatures - different kinds of instabilities - of several brain functions and mental diseases. PMID:21716642

  13. Robust Transient Dynamics and Brain Functions

    PubMed Central

    Rabinovich, Mikhail I.; Varona, Pablo

    2011-01-01

    In the last few decades several concepts of dynamical systems theory (DST) have guided psychologists, cognitive scientists, and neuroscientists to rethink about sensory motor behavior and embodied cognition. A critical step in the progress of DST application to the brain (supported by modern methods of brain imaging and multi-electrode recording techniques) has been the transfer of its initial success in motor behavior to mental function, i.e., perception, emotion, and cognition. Open questions from research in genetics, ecology, brain sciences, etc., have changed DST itself and lead to the discovery of a new dynamical phenomenon, i.e., reproducible and robust transients that are at the same time sensitive to informational signals. The goal of this review is to describe a new mathematical framework – heteroclinic sequential dynamics – to understand self-organized activity in the brain that can explain certain aspects of robust itinerant behavior. Specifically, we discuss a hierarchy of coarse-grain models of mental dynamics in the form of kinetic equations of modes. These modes compete for resources at three levels: (i) within the same modality, (ii) among different modalities from the same family (like perception), and (iii) among modalities from different families (like emotion and cognition). The analysis of the conditions for robustness, i.e., the structural stability of transient (sequential) dynamics, give us the possibility to explain phenomena like the finite capacity of our sequential working memory – a vital cognitive function –, and to find specific dynamical signatures – different kinds of instabilities – of several brain functions and mental diseases. PMID:21716642

  14. Frequency-specific network topologies in the resting human brain.

    PubMed

    Sasai, Shuntaro; Homae, Fumitaka; Watanabe, Hama; Sasaki, Akihiro T; Tanabe, Hiroki C; Sadato, Norihiro; Taga, Gentaro

    2014-01-01

    A community is a set of nodes with dense inter-connections, while there are sparse connections between different communities. A hub is a highly connected node with high centrality. It has been shown that both "communities" and "hubs" exist simultaneously in the brain's functional connectivity network (FCN), as estimated by correlations among low-frequency spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signal changes (0.01-0.10 Hz). This indicates that the brain has a spatial organization that promotes both segregation and integration of information. Here, we demonstrate that frequency-specific network topologies that characterize segregation and integration also exist within this frequency range. In investigating the coherence spectrum among 87 brain regions, we found that two frequency bands, 0.01-0.03 Hz (very low frequency [VLF] band) and 0.07-0.09 Hz (low frequency [LF] band), mainly contributed to functional connectivity. Comparing graph theoretical indices for the VLF and LF bands revealed that the network in the former had a higher capacity for information segregation between identified communities than the latter. Hubs in the VLF band were mainly located within the anterior cingulate cortices, whereas those in the LF band were located in the posterior cingulate cortices and thalamus. Thus, depending on the timescale of brain activity, at least two distinct network topologies contributed to information segregation and integration. This suggests that the brain intrinsically has timescale-dependent functional organizations. PMID:25566037

  15. Frequency-specific network topologies in the resting human brain

    PubMed Central

    Sasai, Shuntaro; Homae, Fumitaka; Watanabe, Hama; Sasaki, Akihiro T.; Tanabe, Hiroki C.; Sadato, Norihiro; Taga, Gentaro

    2014-01-01

    A community is a set of nodes with dense inter-connections, while there are sparse connections between different communities. A hub is a highly connected node with high centrality. It has been shown that both “communities” and “hubs” exist simultaneously in the brain's functional connectivity network (FCN), as estimated by correlations among low-frequency spontaneous fluctuations in functional magnetic resonance imaging (fMRI) signal changes (0.01–0.10 Hz). This indicates that the brain has a spatial organization that promotes both segregation and integration of information. Here, we demonstrate that frequency-specific network topologies that characterize segregation and integration also exist within this frequency range. In investigating the coherence spectrum among 87 brain regions, we found that two frequency bands, 0.01–0.03 Hz (very low frequency [VLF] band) and 0.07–0.09 Hz (low frequency [LF] band), mainly contributed to functional connectivity. Comparing graph theoretical indices for the VLF and LF bands revealed that the network in the former had a higher capacity for information segregation between identified communities than the latter. Hubs in the VLF band were mainly located within the anterior cingulate cortices, whereas those in the LF band were located in the posterior cingulate cortices and thalamus. Thus, depending on the timescale of brain activity, at least two distinct network topologies contributed to information segregation and integration. This suggests that the brain intrinsically has timescale-dependent functional organizations. PMID:25566037

  16. Non-invasive brain-to-brain interface (BBI): establishing functional links between two brains.

    PubMed

    Yoo, Seung-Schik; Kim, Hyungmin; Filandrianos, Emmanuel; Taghados, Seyed Javid; Park, Shinsuk

    2013-01-01

    Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer's intention to stimulate a rat's brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer's intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications. PMID:23573251

  17. Non-Invasive Brain-to-Brain Interface (BBI): Establishing Functional Links between Two Brains

    PubMed Central

    Yoo, Seung-Schik; Kim, Hyungmin; Filandrianos, Emmanuel; Taghados, Seyed Javid; Park, Shinsuk

    2013-01-01

    Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer’s intention to stimulate a rat’s brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer’s intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications. PMID:23573251

  18. Disrupted functional brain networks in autistic toddlers.

    PubMed

    Boersma, Maria; Kemner, Chantal; de Reus, Marcel A; Collin, Guusje; Snijders, Tineke M; Hofman, Dennis; Buitelaar, Jan K; Stam, Cornelis J; van den Heuvel, Martijn P

    2013-01-01

    Communication and integration of information between brain regions plays a key role in healthy brain function. Conversely, disruption in brain communication may lead to cognitive and behavioral problems. Autism is a neurodevelopmental disorder that is characterized by impaired social interactions and aberrant basic information processing. Aberrant brain connectivity patterns have indeed been hypothesized to be a key neural underpinning of autism. In this study, graph analytical tools are used to explore the possible deviant functional brain network organization in autism at a very early stage of brain development. Electroencephalography (EEG) recordings in 12 toddlers with autism (mean age 3.5 years) and 19 control subjects were used to assess interregional functional brain connectivity, with functional brain networks constructed at the level of temporal synchronization between brain regions underlying the EEG electrodes. Children with autism showed a significantly increased normalized path length and reduced normalized clustering, suggesting a reduced global communication capacity already during early brain development. In addition, whole brain connectivity was found to be significantly reduced in these young patients suggesting an overall under-connectivity of functional brain networks in autism. Our findings support the hypothesis of abnormal neural communication in autism, with deviating effects already present at the early stages of brain development. PMID:23259692

  19. Aging and functional brain networks

    SciTech Connect

    Tomasi D.; Tomasi, D.; Volkow, N.D.

    2011-07-11

    Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the 'default-mode' network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting-state data sets corresponding to 913 healthy subjects from a public magnetic resonance imaging database using functional connectivity density mapping (FCDM), a voxelwise and data-driven approach, together with parallel computing. Aging was associated with pronounced long-range FCD decreases in DMN and dorsal attention network (DAN) and with increases in somatosensory and subcortical networks. Aging effects in these networks were stronger for long-range than for short-range FCD and were also detected at the level of the main functional hubs. Females had higher short- and long-range FCD in DMN and lower FCD in the somatosensory network than males, but the gender by age interaction effects were not significant for any of the networks or hubs. These findings suggest that long-range connections may be more vulnerable to aging effects than short-range connections and that, in addition to the DMN, the DAN is also sensitive to aging effects, which could underlie the deterioration of attention processes that occurs with aging.

  20. Dolichol alters brain membrane functions

    SciTech Connect

    Sun, G.Y.; Sun, A.Y.; Schroeder, F.; Wood, G.; Strong, R.

    1986-03-05

    It has been well demonstrated that there is a direct correlation between increase in dolichol level in brain and aging. An abnormally high level of dolichol was found in brain tissue of patients with pathological aging disorders. The aim of this study is to examine the physiological significance of dolichol affecting membrane transport activity and phospholipid acyl group turnover. Dolichol added to synaptic plasma membranes resulted in a biphasic effect on (Na/sup +/, K/sup +/)-ATPase, i.e., an enhancement of activity at low concentrations (5 ..mu..g/125 mg protein) and an inhibition of activity at high concentrations (40-100 ..mu..g). To probe the membrane acyl group turnover, the incorporation of (/sup 14/C)-arachidonate into plasma membrane phospholipids was examined in the presence and absence of dolichol. Dolichol elicited an increase in the incorporation of label into phospholipids. However, the effects varied depending on whether BSA is present. In the absence of BSA, the increase in labeling of phosphatidylinositols is higher than that of phosphatidylcholines. These results suggest that dolichols, when inserted into membranes, may alter membrane functions.

  1. Sugar for the brain: the role of glucose in physiological and pathological brain function

    PubMed Central

    Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A.; Meisel, Andreas

    2013-01-01

    The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease. PMID:23968694

  2. Brain-specific epigenetic markers of schizophrenia.

    PubMed

    Wockner, L F; Morris, C P; Noble, E P; Lawford, B R; Whitehall, V L J; Young, R M; Voisey, J

    2015-01-01

    Epigenetics plays a crucial role in schizophrenia susceptibility. In a previous study, we identified over 4500 differentially methylated sites in prefrontal cortex (PFC) samples from schizophrenia patients. We believe this was the first genome-wide methylation study performed on human brain tissue using the Illumina Infinium HumanMethylation450 Bead Chip. To understand the biological significance of these results, we sought to identify a smaller number of differentially methylated regions (DMRs) of more functional relevance compared with individual differentially methylated sites. Since our schizophrenia whole genome methylation study was performed, another study analysing two separate data sets of post-mortem tissue in the PFC from schizophrenia patients has been published. We analysed all three data sets using the bumphunter function found in the Bioconductor package minfi to identify regions that are consistently differentially methylated across distinct cohorts. We identified seven regions that are consistently differentially methylated in schizophrenia, despite considerable heterogeneity in the methylation profiles of patients with schizophrenia. The regions were near CERS3, DPPA5, PRDM9, DDX43, REC8, LY6G5C and a region on chromosome 10. Of particular interest is PRDM9 which encodes a histone methyltransferase that is essential for meiotic recombination and is known to tag genes for epigenetic transcriptional activation. These seven DMRs are likely to be key epigenetic factors in the aetiology of schizophrenia and normal brain neurodevelopment. PMID:26575221

  3. Structural and functional connectivity in traumatic brain injury

    PubMed Central

    Xiao, Hui; Yang, Yang; Xi, Ji-hui; Chen, Zi-qian

    2015-01-01

    Traumatic brain injury survivors often experience cognitive deficits and neuropsychiatric symptoms. However, the neurobiological mechanisms underlying specific impairments are not fully understood. Advances in neuroimaging techniques (such as diffusion tensor imaging and functional MRI) have given us new insights on structural and functional connectivity patterns of the human brain in both health and disease. The connectome derived from connectivity maps reflects the entire constellation of distributed brain networks. Using these powerful neuroimaging approaches, changes at the microstructural level can be detected through regional and global properties of neuronal networks. Here we will review recent developments in the study of brain network abnormalities in traumatic brain injury, mainly focusing on structural and functional connectivity. Some connectomic studies have provided interesting insights into the neurological dysfunction that occurs following traumatic brain injury. These techniques could eventually be helpful in developing imaging biomarkers of cognitive and neurobehavioral sequelae, as well as predicting outcome and prognosis. PMID:26889200

  4. Promoting Motor Function by Exercising the Brain

    PubMed Central

    Perrey, Stephane

    2013-01-01

    Exercise represents a behavioral intervention that enhances brain health and motor function. The increase in cerebral blood volume in response to physical activity may be responsible for improving brain function. Among the various neuroimaging techniques used to monitor brain hemodynamic response during exercise, functional near-infrared spectroscopy could facilitate the measurement of task-related cortical responses noninvasively and is relatively robust with regard to the subjects’ motion. Although the components of optimal exercise interventions have not been determined, evidence from animal and human studies suggests that aerobic exercise with sufficiently high intensity has neuroprotective properties and promotes motor function. This review provides an insight into the effect of physical activity (based on endurance and resistance exercises) on brain function for producing movement. Since most progress in the study of brain function has come from patients with neurological disorders (e.g., stroke and Parkinson’s patients), this review presents some findings emphasizing training paradigms for restoring motor function. PMID:24961309

  5. Promoting motor function by exercising the brain.

    PubMed

    Perrey, Stephane

    2013-01-01

    Exercise represents a behavioral intervention that enhances brain health and motor function. The increase in cerebral blood volume in response to physical activity may be responsible for improving brain function. Among the various neuroimaging techniques used to monitor brain hemodynamic response during exercise, functional near-infrared spectroscopy could facilitate the measurement of task-related cortical responses noninvasively and is relatively robust with regard to the subjects' motion. Although the components of optimal exercise interventions have not been determined, evidence from animal and human studies suggests that aerobic exercise with sufficiently high intensity has neuroprotective properties and promotes motor function. This review provides an insight into the effect of physical activity (based on endurance and resistance exercises) on brain function for producing movement. Since most progress in the study of brain function has come from patients with neurological disorders (e.g., stroke and Parkinson's patients), this review presents some findings emphasizing training paradigms for restoring motor function. PMID:24961309

  6. Functional specifications for mathematical computations

    SciTech Connect

    Boyle, J.M. ); Harmer, T.J. . Dept. of Computer Science)

    1991-01-01

    Are functional programs useful for specifying numerical computations We believe they certainly are, despite the long-established tradition of using procedural languages for such computations. We have prepared a pure functional specification for an algorithm that solves one-dimensional hyperbolic partial differential equations (PDEs). Using automated program transformations, we have derived a Fortran program from this specification that executes faster on a CRAY X-MP than does the hand-written Fortran implementation of the same algorithm. We discuss the development of the initial specification for the one-dimensional problem and its evolution into a second specification for solving multidimensional hyperbolic PDEs. In this second specification, the dimensionality of the problem is completely parameterized and is given by specifying the set of neighbors of a cell in the grid. Thus, programs can be derived from this specification to solve hyperbolic PDEs of any given dimensionality. Our goal is to elucidate how we approach specifying numerical computations in the functional style and to show how we take advantage of the modularity and abstractness of functional programming to obtain a very high-level representation of the algorithm. We also briefly discuss transformational derivation of efficient programs from such specifications. 13 refs., 1 tab.

  7. Neural Differentiation Modulates the Vertebrate Brain Specific Splicing Program

    PubMed Central

    Madgwick, Alicia; Fort, Philippe; Hanson, Peter S.; Thibault, Philippe; Gaudreau, Marie-Claude; Lutfalla, Georges; Möröy, Tarik; Abou Elela, Sherif; Chaudhry, Bill; Elliott, David J.; Morris, Christopher M.; Venables, Julian P.

    2015-01-01

    Alternative splicing patterns are known to vary between tissues but these patterns have been found to be predominantly peculiar to one species or another, implying only a limited function in fundamental neural biology. Here we used high-throughput RT-PCR to monitor the expression pattern of all the annotated simple alternative splicing events (ASEs) in the Reference Sequence Database, in different mouse tissues and identified 93 brain-specific events that shift from one isoform to another (switch-like) between brain and other tissues. Consistent with an important function, regulation of a core set of 9 conserved switch-like ASEs is highly conserved, as they have the same pattern of tissue-specific splicing in all vertebrates tested: human, mouse and zebrafish. Several of these ASEs are embedded within genes that encode proteins associated with the neuronal microtubule network, and show a dramatic and concerted shift within a short time window of human neural stem cell differentiation. Similarly these exons are dynamically regulated in zebrafish development. These data demonstrate that although alternative splicing patterns often vary between species, there is nonetheless a core set of vertebrate brain-specific ASEs that are conserved between species and associated with neural differentiation. PMID:25993117

  8. Functional Data Analysis in Brain Imaging Studies

    PubMed Central

    Tian, Tian Siva

    2010-01-01

    Functional data analysis (FDA) considers the continuity of the curves or functions, and is a topic of increasing interest in the statistics community. FDA is commonly applied to time-series and spatial-series studies. The development of functional brain imaging techniques in recent years made it possible to study the relationship between brain and mind over time. Consequently, an enormous amount of functional data is collected and needs to be analyzed. Functional techniques designed for these data are in strong demand. This paper discusses three statistically challenging problems utilizing FDA techniques in functional brain imaging analysis. These problems are dimension reduction (or feature extraction), spatial classification in functional magnetic resonance imaging studies, and the inverse problem in magneto-encephalography studies. The application of FDA to these issues is relatively new but has been shown to be considerably effective. Future efforts can further explore the potential of FDA in functional brain imaging studies. PMID:21833205

  9. Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

    PubMed Central

    Kleinridders, Andr; Ferris, Heather A.; Cai, Weikang

    2014-01-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. PMID:24931034

  10. Bioengineered functional brain-like cortical tissue

    PubMed Central

    Tang-Schomer, Min D.; White, James D.; Tien, Lee W.; Schmitt, L. Ian; Valentin, Thomas M.; Graziano, Daniel J.; Hopkins, Amy M.; Omenetto, Fiorenzo G.; Haydon, Philip G.; Kaplan, David L.

    2014-01-01

    The brain remains one of the most important but least understood tissues in our body, in part because of its complexity as well as the limitations associated with in vivo studies. Although simpler tissues have yielded to the emerging tools for in vitro 3D tissue cultures, functional brain-like tissues have not. We report the construction of complex functional 3D brain-like cortical tissue, maintained for months in vitro, formed from primary cortical neurons in modular 3D compartmentalized architectures with electrophysiological function. We show that, on injury, this brain-like tissue responds in vitro with biochemical and electrophysiological outcomes that mimic observations in vivo. This modular 3D brain-like tissue is capable of real-time nondestructive assessments, offering previously unidentified directions for studies of brain homeostasis and injury. PMID:25114234

  11. The development of Human Functional Brain Networks

    PubMed Central

    Power, Jonathan D; Fair, Damien A; Schlaggar, Bradley L

    2010-01-01

    Recent advances in MRI technology have enabled precise measurements of correlated activity throughout the brain, leading to the first comprehensive descriptions of functional brain networks in humans. This article reviews the growing literature on the development of functional networks, from infancy through adolescence, as measured by resting state functional connectivity MRI. We note several limitations of traditional approaches to describing brain networks, and describe a powerful framework for analyzing networks, called graph theory. We argue that characterization of the development of brain systems (e.g. the default mode network) should be comprehensive, considering not only relationships within a given system, but also how these relationships are situated within wider network contexts. We note that, despite substantial reorganization of functional connectivity, several large-scale network properties appear to be preserved across development, suggesting that functional brain networks, even in children, are organized in manners similar to other complex systems. PMID:20826306

  12. 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

  13. Brain Function: Implications for Schooling.

    ERIC Educational Resources Information Center

    Edwards, Clifford H.

    1982-01-01

    The implications of cerebral dominance for curriculum and instruction are enormous. Cognitive style, sex differences, instructional materials preparation and selection, and testing are affected by right or left brain hemisphere dominance. (CJ)

  14. Pain and the brain: Specificity and plasticity of the brain in clinical chronic pain

    PubMed Central

    Apkarian, A.V.; Hashmi, J.A.; Baliki, M.N.

    2010-01-01

    We review recent advances in brain imaging in humans, concentrating on advances in our understanding of the human brain in clinical chronic pain. Understanding regarding anatomical and functional reorganization of the brain in chronic pain is emphasized. We conclude by proposing a brain model for the transition of the human from acute to chronic pain. PMID:21146929

  15. Focused ultrasound modulates region-specific brain activity.

    PubMed

    Yoo, Seung-Schik; Bystritsky, Alexander; Lee, Jong-Hwan; Zhang, Yongzhi; Fischer, Krisztina; Min, Byoung-Kyong; McDannold, Nathan J; Pascual-Leone, Alvaro; Jolesz, Ferenc A

    2011-06-01

    We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders. PMID:21354315

  16. Mitochondrial specific therapeutic targets following brain injury.

    PubMed

    Yonutas, H M; Vekaria, H J; Sullivan, P G

    2016-06-01

    Traumatic brain injury is a complicated disease to treat due to the complex multi-factorial secondary injury cascade that is initiated following the initial impact. This secondary injury cascade causes nonmechanical tissue damage, which is where therapeutic interventions may be efficacious for intervention. One therapeutic target that has shown much promise following brain injury are mitochondria. Mitochondria are complex organelles found within the cell. At a superficial level, mitochondria are known to produce the energy substrate used within the cell called ATP. However, their importance to overall cellular homeostasis is even larger than their production of ATP. These organelles are necessary for calcium cycling, ROS production and play a role in the initiation of cell death pathways. When mitochondria become dysfunctional, they can become dysregulated leading to a loss of cellular homeostasis and eventual cell death. Within this review there will be a deep discussion into mitochondrial bioenergetics followed by a brief discussion into traumatic brain injury and how mitochondria play an integral role in the neuropathological sequelae following an injury. The review will conclude with a discussion pertaining to the therapeutic approaches currently being studied to ameliorate mitochondrial dysfunction following brain injury. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26872596

  17. Determination of Vascular Dementia Brain in Distinct Frequency Bands with Whole Brain Functional Connectivity Patterns

    PubMed Central

    Zhang, Delong; Liu, Bo; Chen, Jun; Peng, Xiaoling; Liu, Xian; Fan, Yuanyuan; Liu, Ming; Huang, Ruiwang

    2013-01-01

    Recent studies have shown that multivariate pattern analysis (MVPA) can be useful for distinguishing brain disorders into categories. Such analyses can substantially enrich and facilitate clinical diagnoses. Using MPVA methods, whole brain functional networks, especially those derived using different frequency windows, can be applied to detect brain states. We constructed whole brain functional networks for groups of vascular dementia (VaD) patients and controls using resting state BOLD-fMRI (rsfMRI) data from three frequency bands - slow-5 (0.01∼0.027 Hz), slow-4 (0.027∼0.073 Hz), and whole-band (0.01∼0.073 Hz). Then we used the support vector machine (SVM), a type of MVPA classifier, to determine the patterns of functional connectivity. Our results showed that the brain functional networks derived from rsfMRI data (19 VaD patients and 20 controls) in these three frequency bands appear to reflect neurobiological changes in VaD patients. Such differences could be used to differentiate the brain states of VaD patients from those of healthy individuals. We also found that the functional connectivity patterns of the human brain in the three frequency bands differed, as did their ability to differentiate brain states. Specifically, the ability of the functional connectivity pattern to differentiate VaD brains from healthy ones was more efficient in the slow-5 (0.01∼0.027 Hz) band than in the other two frequency bands. Our findings suggest that the MVPA approach could be used to detect abnormalities in the functional connectivity of VaD patients in distinct frequency bands. Identifying such abnormalities may contribute to our understanding of the pathogenesis of VaD. PMID:23359801

  18. Toward discovery science of human brain function.

    PubMed

    Biswal, Bharat B; Mennes, Maarten; Zuo, Xi-Nian; Gohel, Suril; Kelly, Clare; Smith, Steve M; Beckmann, Christian F; Adelstein, Jonathan S; Buckner, Randy L; Colcombe, Stan; Dogonowski, Anne-Marie; Ernst, Monique; Fair, Damien; Hampson, Michelle; Hoptman, Matthew J; Hyde, James S; Kiviniemi, Vesa J; Ktter, Rolf; Li, Shi-Jiang; Lin, Ching-Po; Lowe, Mark J; Mackay, Clare; Madden, David J; Madsen, Kristoffer H; Margulies, Daniel S; Mayberg, Helen S; McMahon, Katie; Monk, Christopher S; Mostofsky, Stewart H; Nagel, Bonnie J; Pekar, James J; Peltier, Scott J; Petersen, Steven E; Riedl, Valentin; Rombouts, Serge A R B; Rypma, Bart; Schlaggar, Bradley L; Schmidt, Sein; Seidler, Rachael D; Siegle, Greg J; Sorg, Christian; Teng, Gao-Jun; Veijola, Juha; Villringer, Arno; Walter, Martin; Wang, Lihong; Weng, Xu-Chu; Whitfield-Gabrieli, Susan; Williamson, Peter; Windischberger, Christian; Zang, Yu-Feng; Zhang, Hong-Ying; Castellanos, F Xavier; Milham, Michael P

    2010-03-01

    Although it is being successfully implemented for exploration of the genome, discovery science has eluded the functional neuroimaging community. The core challenge remains the development of common paradigms for interrogating the myriad functional systems in the brain without the constraints of a priori hypotheses. Resting-state functional MRI (R-fMRI) constitutes a candidate approach capable of addressing this challenge. Imaging the brain during rest reveals large-amplitude spontaneous low-frequency (<0.1 Hz) fluctuations in the fMRI signal that are temporally correlated across functionally related areas. Referred to as functional connectivity, these correlations yield detailed maps of complex neural systems, collectively constituting an individual's "functional connectome." Reproducibility across datasets and individuals suggests the functional connectome has a common architecture, yet each individual's functional connectome exhibits unique features, with stable, meaningful interindividual differences in connectivity patterns and strengths. Comprehensive mapping of the functional connectome, and its subsequent exploitation to discern genetic influences and brain-behavior relationships, will require multicenter collaborative datasets. Here we initiate this endeavor by gathering R-fMRI data from 1,414 volunteers collected independently at 35 international centers. We demonstrate a universal architecture of positive and negative functional connections, as well as consistent loci of inter-individual variability. Age and sex emerged as significant determinants. These results demonstrate that independent R-fMRI datasets can be aggregated and shared. High-throughput R-fMRI can provide quantitative phenotypes for molecular genetic studies and biomarkers of developmental and pathological processes in the brain. To initiate discovery science of brain function, the 1000 Functional Connectomes Project dataset is freely accessible at www.nitrc.org/projects/fcon_1000/. PMID:20176931

  19. Entropy changes in brain function.

    PubMed

    Rosso, Osvaldo A

    2007-04-01

    The traditional way of analyzing brain electrical activity, on the basis of electroencephalography (EEG) records, relies mainly on visual inspection and years of training. Although it is quite useful, of course, one has to acknowledge its subjective nature that hardly allows for a systematic protocol. In the present work quantifiers based on information theory and wavelet transform are reviewed. The "relative wavelet energy" provides information about the relative energy associated with different frequency bands present in the EEG and their corresponding degree of importance. The "normalized total wavelet entropy" carries information about the degree of order-disorder associated with a multi-frequency signal response. Their application in the analysis and quantification of short duration EEG signals (event-related potentials) and epileptic EEG records are summarized. PMID:17234291

  20. Language functioning and deficits following pediatric traumatic brain injury.

    PubMed

    Sullivan, Jeremy R; Riccio, Cynthia A

    2010-04-01

    The purpose of this article is to provide a current review of language functioning and deficits following traumatic brain injury (TBI), specifically among the pediatric population. This paper will: (a) outline the manner in which these deficits may impede functioning across environments; (b) review methods of assessing language functioning within this population; and (c) discuss empirically supported interventions to address noted language deficits as they present in pediatric TBI. PMID:20467948

  1. Developing Brain Vital Signs: Initial Framework for Monitoring Brain Function Changes Over Time

    PubMed Central

    Ghosh Hajra, Sujoy; Liu, Careesa C.; Song, Xiaowei; Fickling, Shaun; Liu, Luke E.; Pawlowski, Gabriela; Jorgensen, Janelle K.; Smith, Aynsley M.; Schnaider-Beeri, Michal; Van Den Broek, Rudi; Rizzotti, Rowena; Fisher, Kirk; D'Arcy, Ryan C. N.

    2016-01-01

    Clinical assessment of brain function relies heavily on indirect behavior-based tests. Unfortunately, behavior-based assessments are subjective and therefore susceptible to several confounding factors. Event-related brain potentials (ERPs), derived from electroencephalography (EEG), are often used to provide objective, physiological measures of brain function. Historically, ERPs have been characterized extensively within research settings, with limited but growing clinical applications. Over the past 20 years, we have developed clinical ERP applications for the evaluation of functional status following serious injury and/or disease. This work has identified an important gap: the need for a clinically accessible framework to evaluate ERP measures. Crucially, this enables baseline measures before brain dysfunction occurs, and might enable the routine collection of brain function metrics in the future much like blood pressure measures today. Here, we propose such a framework for extracting specific ERPs as potential “brain vital signs.” This framework enabled the translation/transformation of complex ERP data into accessible metrics of brain function for wider clinical utilization. To formalize the framework, three essential ERPs were selected as initial indicators: (1) the auditory N100 (Auditory sensation); (2) the auditory oddball P300 (Basic attention); and (3) the auditory speech processing N400 (Cognitive processing). First step validation was conducted on healthy younger and older adults (age range: 22–82 years). Results confirmed specific ERPs at the individual level (86.81–98.96%), verified predictable age-related differences (P300 latency delays in older adults, p < 0.05), and demonstrated successful linear transformation into the proposed brain vital sign (BVS) framework (basic attention latency sub-component of BVS framework reflects delays in older adults, p < 0.05). The findings represent an initial critical step in developing, extracting, and characterizing ERPs as vital signs, critical for subsequent evaluation of dysfunction in conditions like concussion and/or dementia.

  2. The connection between rhythmicity and brain function.

    PubMed

    Thaut, M H; Kenyon, G P; Schauer, M L; McIntosh, G C

    1999-01-01

    Although rhythm and music are not entirely synonymous terms, rhythm constitutes one of the most essential structural and organizational elements of music. When considering the effect of music on human adaptation, the profound effect of rhythm on the motor system strongly suggests that the time structure of music is the essential element relating music specifically to motor behavior. Why the motor system appears so sensitive to auditory priming and timing stimulation can only be partially answered so far. The high-performance function of the auditory system regarding processing of time information makes good functional sense within the constraints of auditory sensory processing. Thus, the motor system sensitivity to auditory entrainment may simply be an evolutionary useful function of taking advantage of the specific and unique aspects of auditory information processing for enhanced control and organization of motor behavior; e.g, in the time domain. Unlike processes in the motor system, many other physiological processes cannot be effectively entrained by external sensory stimuli. For example, there is probably a very good protective reason why other cyclical physiological processes (e.g., autonomic processes such as heart rate) have only very limited entrainment capacity to external rhythmic cues. Some of the basic auditory-motor arousal connections may also have their basis in adaptive evolutionary processes related to survival behavior; e.g., in fight or flight reactions. Much of the "why" in auditory-motor interactions, however, remains unknown heuristically. In the absence of this knowledge, great care should be taken to not compensate for this lack of understanding of specific cause and effect processes by assigning anthropomorphic descriptions to the behavior of biological and physical systems. The unraveling of the perceptual, physiological, and neuroanatomical basis of the interaction between rhythm and movement has been, and continues to be, a fascinating endeavor with important ramifications for the study of brain function, sensory perception, and motor behavior. One of the most exciting findings in this research, however, may be the evidence that the interaction between auditory rhythm and physical response can be effectively harnessed for specific therapeutic purposes in the rehabilitation of persons with movement disorders. PMID:10101675

  3. Tracking the Brain's Functional Coupling Dynamics over Development.

    PubMed

    Hutchison, R Matthew; Morton, J Bruce

    2015-04-29

    The transition from childhood to adulthood is marked by pronounced functional and structural brain transformations that impact cognition and behavior. Here, we use a functional imaging approach to reveal dynamic changes in coupling strength between networks and the expression of discrete brain configurations over human development during rest and a cognitive control task. Although the brain's repertoire of functional states was generally preserved across ages, state-specific temporal features, such as the frequency of expression and the amount of time spent in select states, varied by age in ways that were dependent on condition. Increasing age was associated with greater variability of connection strengths across time at rest, while there was a selective inversion of this effect in higher-order networks during implementation of cognitive control. The results suggest that development is characterized by the modification of dynamic coupling to both maximize and constrain functional variability in response to ongoing cognitive and behavioral requirements. PMID:25926460

  4. Mapping brain function in freely moving subjects

    PubMed Central

    Holschneider, Daniel P.; Maarek, Jean-Michel I.

    2014-01-01

    Expression of many fundamental mammalian behaviors such as, for example, aggression, mating, foraging or social behaviors, depend on locomotor activity. A central dilemma in the functional neuroimaging of these behaviors has been the fact that conventional neuroimaging techniques generally rely on immobilization of the subject, which extinguishes all but the simplest activity. Ideally, imaging could occur in freely moving subjects, while presenting minimal interference with the subject’s natural behavior. Here we provide an overview of several approaches that have been undertaken in the past to achieve this aim in both tethered and freely moving animals, as well as in nonrestrained human subjects. Applications of specific radiotracers to single photon emission computed tomography and positron emission tomography are discussed in which brain activation is imaged after completion of the behavioral task and capture of the tracer. Potential applications to clinical neuropsychiatry are discussed, as well as challenges inherent to constraint-free functional neuroimaging. Future applications of these methods promise to increase our understanding of the neural circuits underlying mammalian behavior in health and disease. PMID:15465134

  5. Detecting disease-specific patterns of brain structure using cortical pattern matching and a population-based probabilistic brain atlas

    PubMed Central

    Thompson, Paul M.; Mega, Michael S.; Vidal, Christine; Rapoport, Judith L.; Toga, Arthur W.

    2008-01-01

    The rapid creation of comprehensive brain image databases mandates the development of mathematical algorithms to uncover disease specific patterns of brain structure and function in human populations. We describe our construction of probabilistic atlases that store detailed information on how the brain varies across age and gender, across time, in health and disease, and in large human populations. Specifically, we introduce a mathematical framework based on covariant partial differential equations (PDEs), pull-backs of mappings under harmonic flows, and high-dimensional random tensor fields to encode variations in cortical patterning, asymmetry and tissue distribution in a population-based brain image database (N =94 scans). We use this information to detect disease-specific abnormalities in Alzheimer's disease and schizophrenia, including dynamic changes over time. Illustrative examples are chosen to show how group patterns of cortical organization, asymmetry, and disease-specific trends can be resolved that are not apparent in individual brain images. Finally, we create four-dimensional (4D) maps that store probabilistic information on the dynamics of brain change in development and disease. Digital atlases that generate these maps show considerable promise in identifying general patterns of structural and functional variation in diseased populations, and revealing how these features depend on demographic, genetic, clinical and therapeutic parameters. PMID:21218175

  6. Progesterone Receptors: Form and Function in Brain

    PubMed Central

    Brinton, Roberta Diaz; Thompson, Richard F.; Foy, Michael R.; Baudry, Michel; Wang, JunMing; Finch, Caleb E; Morgan, Todd E.; Stanczyk, Frank Z.; Pike, Christian J.; Nilsen, Jon

    2008-01-01

    Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRβ and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and / or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging. PMID:18374402

  7. Strengthening connections: functional connectivity and brain plasticity

    PubMed Central

    Kelly, Clare; Castellanos, F. Xavier

    2014-01-01

    The ascendancy of functional neuroimaging has facilitated the addition of network-based approaches to the neuropsychologist’s toolbox for evaluating the sequelae of brain insult. In particular, intrinsic functional connectivity (iFC) mapping of resting state fMRI (R-fMRI) data constitutes an ideal approach to measuring macro-scale networks in the human brain. Beyond the value of iFC mapping for charting how the functional topography of the brain is altered by insult and injury, iFC analyses can provide insights into effects of experience-dependent plasticity at the macro level of large-scale functional networks. Such insights are foundational to the design of training and remediation interventions that will best facilitate recovery of function. In this review, we consider what is currently known about the origin and function of iFC in the brain, and how this knowledge is informative in neuropsychological settings. We then summarize studies that have examined experience-driven plasticity of iFC in healthy control participants, and frame these findings in terms of a schema that may aid in the interpretation of results and the generation of hypothesis for rehabilitative studies. Finally, we outline some caveats to the R-fMRI approach, as well as some current developments that are likely to bolster the utility of the iFC paradigm for neuropsychology. PMID:24496903

  8. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    PubMed

    Li, Guangye; Zhang, Dingguo

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

  9. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain

    PubMed Central

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

  10. [Brain function and artificial respiration].

    PubMed

    Prien, T; Lawin, P; Schoeppner, H

    1984-12-01

    Haemodynamic changes (cerebral perfusion pressure, cerebral blood flow) and variations of blood gases (especially paCO2) induced by mechanical ventilation, can influence cerebral function. The cerebral response to these changes is modified by the individual pathophysiology of the cranial contents. The cerebral mechanisms of adaptation allow a safe ventilation of a patient without cerebral disorders, provided ventilation is within normal clinical limits. In patients, however, whose mechanisms of adaption are impaired locally or globally, the pathophysiological situation may become grossly changed by variations in the ventilatory pattern. A therapeutical application of this interaction is controlled hyperventilation to lower intracranial pressure. On the other hand, changes in the ventilatory pattern (variation of PEEP-level, variation of minute volume, bronchial toilet) can impair cerebral function critically. As the individual reactions cannot be predicted in this group of patients, monitoring of haemodynamic parameters (MAP, CVP, CO), blood gases, intracranial pressure, and EEG is of utmost importance. PMID:6441481

  11. Specific glial functions contribute to schizophrenia susceptibility.

    PubMed

    Goudriaan, Andrea; de Leeuw, Christiaan; Ripke, Stephan; Hultman, Christina M; Sklar, Pamela; Sullivan, Patrick F; Smit, August B; Posthuma, Danielle; Verheijen, Mark H G

    2014-07-01

    Schizophrenia is a highly polygenic brain disorder. The main hypothesis for disease etiology in schizophrenia primarily focuses on the role of dysfunctional synaptic transmission. Previous studies have therefore directed their investigations toward the role of neuronal dysfunction. However, recent studies have shown that apart from neurons, glial cells also play a major role in synaptic transmission. Therefore, we investigated the potential causal involvement of the 3 principle glial cell lineages in risk to schizophrenia. We performed a functional gene set analysis to test for the combined effects of genetic variants in glial type-specific genes for association with schizophrenia. We used genome-wide association data from the largest schizophrenia sample to date, including 13 689 cases and 18 226 healthy controls. Our results show that astrocyte and oligodendrocyte gene sets, but not microglia gene sets, are associated with an increased risk for schizophrenia. The astrocyte and oligodendrocyte findings are related to astrocyte signaling at the synapse, myelin membrane integrity, glial development, and epigenetic control. Together, these results show that genetic alterations underlying specific glial cell type functions increase susceptibility to schizophrenia and provide evidence that the neuronal hypothesis of schizophrenia should be extended to include the role of glia. PMID:23956119

  12. Functional imaging of the brain by MRI

    NASA Astrophysics Data System (ADS)

    LeBihan, D.; Cuenod, Charles-Andre; Turner, J. R.; Jezzard, P.; Bonnerot, Valerie; Zeffiro, Thomas A.

    1993-08-01

    Recent developments in Magnetic Resonance Imaging (MRI) enabling imaging of hemodynamics and metabolism hold significant promise in the noninvasive evaluation of normal and abnormal brain function. Among several methods, the most successful approach exploits the sensitivity of MRI to changes in the oxygenation status of hemoglobin (oxy/deoxyhemoglobin) in red blood cells related to local variations in blood flow and oxygen consumption in tissues. In cerebral cortex, such variations may be induced by external stimuli or internal cognitive processes. Typically, MRI signal slightly increases when brain is activated due to increase in oxygen supply (blood flow). These studies suggest that MRI may be the method of choice to study mental and cognitive processes underlying the function of the human brain.

  13. Integrating Retinoic Acid Signaling with Brain Function

    ERIC Educational Resources Information Center

    Luo, Tuanlian; Wagner, Elisabeth; Drager, Ursula C.

    2009-01-01

    The vitamin A derivative retinoic acid (RA) regulates the transcription of about a 6th of the human genome. Compelling evidence indicates a role of RA in cognitive activities, but its integration with the molecular mechanisms of higher brain functions is not known. Here we describe the properties of RA signaling in the mouse, which point to…

  14. Classroom Seating and Functional Brain Asymmetry

    ERIC Educational Resources Information Center

    Gur, Raquel E.; And Others

    1975-01-01

    This study examined the relationship between functional brain assymetry, as measured by the characteristic direction of eye movements in response to face-to-face questioning, and sitting on the left or right side of a classroom. Results are congruent with other findings comparing right and left movers. (Author/BJG)

  15. Integrating Retinoic Acid Signaling with Brain Function

    ERIC Educational Resources Information Center

    Luo, Tuanlian; Wagner, Elisabeth; Drager, Ursula C.

    2009-01-01

    The vitamin A derivative retinoic acid (RA) regulates the transcription of about a 6th of the human genome. Compelling evidence indicates a role of RA in cognitive activities, but its integration with the molecular mechanisms of higher brain functions is not known. Here we describe the properties of RA signaling in the mouse, which point to

  16. Electromagnetic inverse applications for functional brain imaging

    SciTech Connect

    Wood, C.C.

    1997-10-01

    This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). This project addresses an important mathematical and computational problem in functional brain imaging, namely the electromagnetic {open_quotes}inverse problem.{close_quotes} Electromagnetic brain imaging techniques, magnetoencephalography (MEG) and electroencephalography (EEG), are based on measurements of electrical potentials and magnetic fields at hundreds of locations outside the human head. The inverse problem is the estimation of the locations, magnitudes, and time-sources of electrical currents in the brain from surface measurements. This project extends recent progress on the inverse problem by combining the use of anatomical constraints derived from magnetic resonance imaging (MRI) with Bayesian and other novel algorithmic approaches. The results suggest that we can achieve significant improvements in the accuracy and robustness of inverse solutions by these two approaches.

  17. Homological scaffolds of brain functional networks.

    PubMed

    Petri, G; Expert, P; Turkheimer, F; Carhart-Harris, R; Nutt, D; Hellyer, P J; Vaccarino, F

    2014-12-01

    Networks, as efficient representations of complex systems, have appealed to scientists for a long time and now permeate many areas of science, including neuroimaging (Bullmore and Sporns 2009 Nat. Rev. Neurosci. 10, 186-198. (doi:10.1038/nrn2618)). Traditionally, the structure of complex networks has been studied through their statistical properties and metrics concerned with node and link properties, e.g. degree-distribution, node centrality and modularity. Here, we study the characteristics of functional brain networks at the mesoscopic level from a novel perspective that highlights the role of inhomogeneities in the fabric of functional connections. This can be done by focusing on the features of a set of topological objects-homological cycles-associated with the weighted functional network. We leverage the detected topological information to define the homological scaffolds, a new set of objects designed to represent compactly the homological features of the correlation network and simultaneously make their homological properties amenable to networks theoretical methods. As a proof of principle,we apply these tools to compare resting state functional brain activity in 15 healthy volunteers after intravenous infusion of placebo and psilocybin-the main psychoactive component of magic mushrooms. The results show that the homological structure of the brain's functional patterns undergoes a dramatic change post-psilocybin, characterized by the appearance of many transient structures of low stability and of a small number of persistent ones that are not observed in the case of placebo. PMID:25401177

  18. Homological scaffolds of brain functional networks

    PubMed Central

    Petri, G.; Expert, P.; Turkheimer, F.; Carhart-Harris, R.; Nutt, D.; Hellyer, P. J.; Vaccarino, F.

    2014-01-01

    Networks, as efficient representations of complex systems, have appealed to scientists for a long time and now permeate many areas of science, including neuroimaging (Bullmore and Sporns 2009 Nat. Rev. Neurosci. 10, 186–198. (doi:10.1038/nrn2618)). Traditionally, the structure of complex networks has been studied through their statistical properties and metrics concerned with node and link properties, e.g. degree-distribution, node centrality and modularity. Here, we study the characteristics of functional brain networks at the mesoscopic level from a novel perspective that highlights the role of inhomogeneities in the fabric of functional connections. This can be done by focusing on the features of a set of topological objects—homological cycles—associated with the weighted functional network. We leverage the detected topological information to define the homological scaffolds, a new set of objects designed to represent compactly the homological features of the correlation network and simultaneously make their homological properties amenable to networks theoretical methods. As a proof of principle, we apply these tools to compare resting-state functional brain activity in 15 healthy volunteers after intravenous infusion of placebo and psilocybin—the main psychoactive component of magic mushrooms. The results show that the homological structure of the brain's functional patterns undergoes a dramatic change post-psilocybin, characterized by the appearance of many transient structures of low stability and of a small number of persistent ones that are not observed in the case of placebo. PMID:25401177

  19. Electroencephalographic imaging of higher brain function

    NASA Technical Reports Server (NTRS)

    Gevins, A.; Smith, M. E.; McEvoy, L. K.; Leong, H.; Le, J.

    1999-01-01

    High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

  20. Joint brain connectivity estimation from diffusion and functional MRI data

    NASA Astrophysics Data System (ADS)

    Chu, Shu-Hsien; Lenglet, Christophe; Parhi, Keshab K.

    2015-03-01

    Estimating brain wiring patterns is critical to better understand the brain organization and function. Anatomical brain connectivity models axonal pathways, while the functional brain connectivity characterizes the statistical dependencies and correlation between the activities of various brain regions. The synchronization of brain activity can be inferred through the variation of blood-oxygen-level dependent (BOLD) signal from functional MRI (fMRI) and the neural connections can be estimated using tractography from diffusion MRI (dMRI). Functional connections between brain regions are supported by anatomical connections, and the synchronization of brain activities arises through sharing of information in the form of electro-chemical signals on axon pathways. Jointly modeling fMRI and dMRI data may improve the accuracy in constructing anatomical connectivity as well as functional connectivity. Such an approach may lead to novel multimodal biomarkers potentially able to better capture functional and anatomical connectivity variations. We present a novel brain network model which jointly models the dMRI and fMRI data to improve the anatomical connectivity estimation and extract the anatomical subnetworks associated with specific functional modes by constraining the anatomical connections as structural supports to the functional connections. The key idea is similar to a multi-commodity flow optimization problem that minimizes the cost or maximizes the efficiency for flow configuration and simultaneously fulfills the supply-demand constraint for each commodity. In the proposed network, the nodes represent the grey matter (GM) regions providing brain functionality, and the links represent white matter (WM) fiber bundles connecting those regions and delivering information. The commodities can be thought of as the information corresponding to brain activity patterns as obtained for instance by independent component analysis (ICA) of fMRI data. The concept of information flow is introduced and used to model the propagation of information between GM areas through WM fiber bundles. The link capacity, i.e., ability to transfer information, is characterized by the relative strength of fiber bundles, e.g., fiber count gathered from the tractography of dMRI data. The node information demand is considered to be proportional to the correlation between neural activity at various cortical areas involved in a particular functional mode (e.g. visual, motor, etc.). These two properties lead to the link capacity and node demand constraints in the proposed model. Moreover, the information flow of a link cannot exceed the demand from either end node. This is captured by the feasibility constraints. Two different cost functions are considered in the optimization formulation in this paper. The first cost function, the reciprocal of fiber strength represents the unit cost for information passing through the link. In the second cost function, a min-max (minimizing the maximal link load) approach is used to balance the usage of each link. Optimizing the first cost function selects the pathway with strongest fiber strength for information propagation. In the second case, the optimization procedure finds all the possible propagation pathways and allocates the flow proportionally to their strength. Additionally, a penalty term is incorporated with both the cost functions to capture the possible missing and weak anatomical connections. With this set of constraints and the proposed cost functions, solving the network optimization problem recovers missing and weak anatomical connections supported by the functional information and provides the functional-associated anatomical subnetworks. Feasibility is demonstrated using realistic diffusion and functional MRI phantom data. It is shown that the proposed model recovers the maximum number of true connections, with fewest number of false connections when compared with the connectivity derived from a joint probabilistic model using the expectation-maximization (EM) algorithm presented in a prior work. We also apply the proposed method to data provided by the Human Connectome Project (HCP).

  1. Functional Connectivity Hubs and Networks in the Awake Marmoset Brain

    PubMed Central

    Belcher, Annabelle M.; Yen, Cecil Chern-Chyi; Notardonato, Lucia; Ross, Thomas J.; Volkow, Nora D.; Yang, Yihong; Stein, Elliot A.; Silva, Afonso C.; Tomasi, Dardo

    2016-01-01

    In combination with advances in analytical methods, resting-state fMRI is allowing unprecedented access to a better understanding of the network organization of the brain. Increasing evidence suggests that this architecture may incorporate highly functionally connected nodes, or “hubs”, and we have recently proposed local functional connectivity density (lFCD) mapping to identify highly-connected nodes in the human brain. Here, we imaged awake nonhuman primates to test whether, like the human brain, the marmoset brain contains FC hubs. Ten adult common marmosets (Callithrix jacchus) were acclimated to mild, comfortable restraint using individualized helmets. Following restraint training, resting BOLD data were acquired during eight consecutive 10 min scans for each subject. lFCD revealed prominent cortical and subcortical hubs of connectivity across the marmoset brain; specifically, in primary and secondary visual cortices (V1/V2), higher-order visual association areas (A19M/V6[DM]), posterior parietal and posterior cingulate areas (PGM and A23b/A31), thalamus, dorsal and ventral striatal areas (caudate, putamen, lateral septal nucleus, and anterior cingulate cortex (A24a). lFCD hubs were highly connected to widespread areas of the brain, and further revealed significant network-network interactions. These data provide a baseline platform for future investigations in a nonhuman primate model of the brain’s network topology. PMID:26973476

  2. The Role of Sleep in Emotional Brain Function

    PubMed Central

    Goldstein, Andrea N.; Walker, Matthew P.

    2014-01-01

    Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by longstanding clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (1) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep, (2) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning, and (3) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on post-traumatic stress disorder and major depression. PMID:24499013

  3. Differential Synchronization in Default and Task-Specific Networks of the Human Brain

    PubMed Central

    Kirschner, Aaron; Kam, Julia Wing Yan; Handy, Todd C.; Ward, Lawrence M.

    2012-01-01

    On a regional scale the brain is organized into dynamic functional networks. The activity within one of these, the default network, can be dissociated from that in other task-specific networks. All brain networks are connected structurally but evidently are only transiently connected functionally. One hypothesis as to how such transient functional coupling occurs is that network formation and dissolution is mediated by increases and decreases in oscillatory synchronization between constituent brain regions. If so, then we should be able to find transient differences in intra-network synchronization between the default network and a task-specific network. In order to investigate this hypothesis we conducted two experiments in which subjects engaged in a Sustained Attention to Response Task while having brain activity recorded via high-density electroencephalography (EEG). We found that during periods when attention was focused internally (mind wandering) there was significantly more neural phase synchronization between brain regions associated with the default network, whereas during periods when subjects were focused on performing the visual task there was significantly more neural phase synchrony within a task-specific brain network that shared some of the same brain regions. These differences in network synchrony occurred in each of theta, alpha, and gamma frequency bands. A similar pattern of differential oscillatory power changes, indicating modulation of local synchronization by attention state, was also found. These results provide further evidence that the human brain is intrinsically organized into default and task-specific brain networks, and confirm that oscillatory synchronization is a potential mechanism for functional coupling within these networks. PMID:22661936

  4. Structural and functional brain imaging in schizophrenia.

    PubMed Central

    Cleghorn, J M; Zipursky, R B; List, S J

    1991-01-01

    We present an evaluation of the contribution of structural and functional brain imaging to our understanding of schizophrenia. Methodological influences on the validity of the data generated by these new technologies include problems with measurement and clinical and anatomic heterogeneity. These considerations greatly affect the interpretation of the data generated by these technologies. Work in these fields to date, however, has produced strong evidence which suggests that schizophrenia is a disease which involves abnormalities in the structure and function of many brain areas. Structural brain imaging studies of schizophrenia using computed tomography (CT) and magnetic resonance imaging (MRI) are reviewed and their contribution to current theories of the pathogenesis of schizophrenia are discussed. Positron emission tomography (PET) studies of brain metabolic activity and dopamine receptor binding in schizophrenia are summarized and the critical questions raised by these studies are outlined. Future studies in these fields have the potential to yield critical insights into the pathophysiology of schizophrenia; new directions for studies of schizophrenia using these technologies are identified. PMID:1911736

  5. Individual diversity of functional brain network economy.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Ganger, Sebastian; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

    2015-04-01

    On average, brain network economy represents a trade-off between communication efficiency, robustness, and connection cost, although an analogous understanding on an individual level is largely missing. Evaluating resting-state networks of 42 healthy participants with seven Tesla functional magnetic resonance imaging and graph theory revealed that not even half of all possible connections were common across subjects. The strongest similarities among individuals were observed for interhemispheric and/or short-range connections, which may relate to the essential feature of the human brain to develop specialized systems within each hemisphere. Despite this marked variability in individual network architecture, all subjects exhibited equal small-world properties. Furthermore, interdependency between four major network economy metrics was observed across healthy individuals. The characteristic path length was associated with the clustering coefficient (peak correlation r=0.93), the response to network attacks (r=-0.97), and the physical connection cost in three-dimensional space (r=-0.62). On the other hand, clustering was negatively related to attack response (r=-0.75) and connection cost (r=-0.59). Finally, increased connection cost was associated with better response to attacks (r=0.65). This indicates that functional brain networks with high global information transfer also exhibit strong network resilience. However, it seems that these advantages come at the cost of decreased local communication efficiency and increased physical connection cost. Except for wiring length, the results were replicated on a subsample at three Tesla (n=20). These findings highlight the finely tuned interrelationships between different parameters of brain network economy. Moreover, the understanding of the individual diversity of functional brain network economy may provide further insights in the vulnerability to mental and neurological disorders. PMID:25411715

  6. Encoding and Retrieving Faces and Places: Distinguishing Process- and Stimulus-Specific Differences in Brain Activity

    ERIC Educational Resources Information Center

    Prince, Steven E.; Dennis, Nancy A.; Cabeza, Roberto

    2009-01-01

    Among the most fundamental issues in cognitive neuroscience is how the brain may be organized into process-specific and stimulus-specific regions. In the episodic memory domain, most functional neuroimaging studies have focused on the former dimension, typically investigating the neural correlates of various memory processes. Thus, there is little…

  7. Encoding and Retrieving Faces and Places: Distinguishing Process- and Stimulus-Specific Differences in Brain Activity

    ERIC Educational Resources Information Center

    Prince, Steven E.; Dennis, Nancy A.; Cabeza, Roberto

    2009-01-01

    Among the most fundamental issues in cognitive neuroscience is how the brain may be organized into process-specific and stimulus-specific regions. In the episodic memory domain, most functional neuroimaging studies have focused on the former dimension, typically investigating the neural correlates of various memory processes. Thus, there is little

  8. Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner.

    PubMed

    Tai, S; Hyatt, W S; Gu, C; Franks, L N; Vasiljevik, T; Brents, L K; Prather, P L; Fantegrossi, W E

    2015-12-01

    These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ∆(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ∆(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.0mg/kg or 10.0mg/kg, respectively) or a maximally hypothermic dose of 30.0mg/kg ∆(9)-THC once per day for 5 consecutive days while core temperature and locomotor activity were monitored via biotelemetry. Repeated administration of all drugs resulted in tolerance to hypothermic effects, but not locomotor effects, and this tolerance was still evident 14 days after the last drug administration. Further studies treated mice with 30.0mg/kg ∆(9)-THC once per day for 4 days, then tested with SCBs on day 5. Mice with a ∆(9)-THC history were cross-tolerant to both SCBs, and this cross-tolerance also persisted 14 days after testing. Select brain regions from chronically treated mice were examined for changes in CB1 receptor expression and function. Expression and function of hypothalamic CB1Rs were reduced in mice receiving chronic drugs, but cortical CB1R expression and function were not altered. Collectively, these data demonstrate that repeated ∆(9)-THC, JWH-018 and JWH-073 can induce long-lasting tolerance to some in vivo effects, which is likely mediated by region-specific downregulation and desensitization of CB1Rs. PMID:26361728

  9. Brain function in social anxiety disorder.

    PubMed

    Argyropoulos, S V; Bell, C J; Nutt, D J

    2001-12-01

    What have these studies revealed about SAD? First, few studies have been performed so far, with even fewer replications. Most of the work has been exploratory in nature and follows the paradigms used in PD. This approach has been justifiably criticized. The use of psychological (naturalistic) challenges may be more appropriate in SP than chemical challenges. The paradigms of public speaking, autobiographical scripts, or similar behavioral challenges merit further use, exploration, and validation if symptoms resembling those of the condition proper are to be induced in experimental circumstances. However, some tentative conclusions can be drawn from the research performed so far. There is no enough evidence to support the presence of structural brain abnormality in SAD. Admittedly, such a finding would have been very unlikely. On the other hand, evidence of subtle functional abnormalities is accumulating. On the nosologic question, there appear to be differences from PD. While in some challenges (e.g., CO2 and pentagastrin) the two conditions differ only in degree, in others (e.g., lactate, caffeine, and flumazenil), the separation is clearer. Equally, there is a strong argument to differentiate the generalized from the specific form of social anxiety on the basis of substantial (albeit accidental) findings outlined earlier. More sophisticated neuroimaging techniques, directly comparing patients from both groups before and after pharmacologic or psychological treatment, should provide more conclusive evidence on this issue. What might also help future research is the integration of biological investigations with specific personality profiles. In one study, SAD patients scored low in novelty seeking, self-directedness and cooperativeness and high in harm avoidance. It has been hypothesized that such results indicate serotonergic and dopaminergic dysregulation, which is consistent with the findings described earlier. The best evidence for neurotransmitter abnormality so far is for altered dopamine function at the level of the basal ganglia, either pre- or postsynaptic, which may result in reduced basal ganglia function so that the normal fluidity of social motor functions (e.g., smiling, eye movements, and speech) are impaired, thus leading to the cognitive symptoms of social anxiety and the subsequent generation of avoidance behavior. Such patients should respond poorly to antipsychotics, and additional challenges with these drugs could be used to test this theory. Furthermore, more research needs to be done to elucidate the mechanism by which SSRIs work in SAD. Neuroanatomical models of social anxiety (Fig. 4) [see structure: Text], explaining the site of action of drugs and psychological treatments, have been proposed in recent years. Central to these models is the notion of an innate anxiety circuit, which could be tentatively identified with the behavioral inhibition system, the septohippocampal system. This area receives 5-HT, NE, and dopamine input and has connections with the cortex and limbic structures. The relevance of these models remains to be assessed in experiments that are specifically designed to test them. PMID:11723629

  10. When "altering brain function" becomes "mind control".

    PubMed

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

    Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control. PMID:25352789

  11. Common and specific brain responses to scenic emotional stimuli.

    PubMed

    Radua, Joaquim; Sarr, Salvador; Vigo, Teresa; Alonso-Lana, Silvia; Bonnn, C Mar; Ortiz-Gil, Jordi; Canales-Rodrguez, Erick J; Maristany, Teresa; Vieta, Eduard; Mckenna, Peter J; Salvador, Raymond; Pomarol-Clotet, Edith

    2014-07-01

    Processing of emotions has been an enduring topic of interest in neuroimaging research, but studies have mostly used facial emotional stimuli. The aim of this study was to determine neural networks involved in emotion processing using scenic emotional visual stimuli. One hundred and twenty photographs from the International Affective Picture System (IAPS), including ecological scenes of disgust, fear, happiness, and sadness, were presented to 40 healthy participants while they underwent functional magnetic imaging resonance (fMRI). Afterwards they evaluated the emotional content of the pictures in an offline task. The occipito-temporal cortex and the amygdala-hippocampal complex showed a non-specific emotion-related activation, which was more marked in response to negative emotions than to happiness. The temporo-parietal cortex and the ventral anterior cingulate gyrus showed deactivation, with the former being marked for all emotions except fear and the latter being most marked for disgust. The fusiform gyrus showed activation in response to disgust and deactivation in response to happiness or sadness. Brain regions involved in processing of scenic emotion therefore resemble those reported for facial expressions of emotion in that they respond to a range of different emotions, although there appears to be specificity in the intensity and direction of the response. PMID:23700105

  12. Brain Function Lateralization and Language Acquisition: the Evidence from Japanese.

    ERIC Educational Resources Information Center

    Sanches, Mary

    1979-01-01

    Presents evidence of differences in brain function lateralization between Japanese-speakers and speakers of Indo-European languages, and suggests that current conceptualizations of brain function specialization are not adequate. (AM)

  13. Projection-specific characteristics of retinal input to the brain.

    PubMed

    Gauvain, Gregory; Murphy, Gabe J

    2015-04-22

    The brain receives information about the direction of object motion from several types of retinal ganglion cells (RGCs). On-Off direction-selective (DS) RGCs respond preferentially to stimuli moving quickly in one of four directions and provide a significant (but difficult to quantify) fraction of RGC input to the SC. On DS RGCs, in comparison, respond preferentially to stimuli moving slowly in one of three directions and are thought to only target retinorecipient nuclei comprising the accessory optic system, e.g., the medial terminal nucleus (MTN). To determine the fraction of SC-projecting RGCs that exhibit direction selectivity, and the specificity with which On-Off and On DS RGCs target retinorecipient areas, we performed optical and electrophysiological recordings from RGCs retrogradely labeled from the mouse SC and MTN. We found, surprisingly, that both On-Off and On DS RGCs innervate the SC; collectively they constitute nearly 40% of SC-projecting RGCs. In comparison, only On DS RGCs project to the MTN. Subsequent experiments revealed that individual On DS RGCs innervate either the SC or MTN and exhibit robust projection-specific differences in somatodendritic morphology, cellular excitability, and light-evoked activity; several projection-specific differences in the output of On DS RGCs correspond closely to differences in excitatory synaptic input the cells receive. Our results reveal a robust projection of On DS RGCs to the SC, projection-specific differences in the response properties of On DS RGCs, and biophysical and synaptic mechanisms that underlie these functional differences. PMID:25904807

  14. Projection-Specific Characteristics of Retinal Input to the Brain

    PubMed Central

    Gauvain, Gregory

    2015-01-01

    The brain receives information about the direction of object motion from several types of retinal ganglion cells (RGCs). On-Off direction-selective (DS) RGCs respond preferentially to stimuli moving quickly in one of four directions and provide a significant (but difficult to quantify) fraction of RGC input to the SC. On DS RGCs, in comparison, respond preferentially to stimuli moving slowly in one of three directions and are thought to only target retinorecipient nuclei comprising the accessory optic system, e.g., the medial terminal nucleus (MTN). To determine the fraction of SC-projecting RGCs that exhibit direction selectivity, and the specificity with which On-Off and On DS RGCs target retinorecipient areas, we performed optical and electrophysiological recordings from RGCs retrogradely labeled from the mouse SC and MTN. We found, surprisingly, that both On-Off and On DS RGCs innervate the SC; collectively they constitute nearly 40% of SC-projecting RGCs. In comparison, only On DS RGCs project to the MTN. Subsequent experiments revealed that individual On DS RGCs innervate either the SC or MTN and exhibit robust projection-specific differences in somatodendritic morphology, cellular excitability, and light-evoked activity; several projection-specific differences in the output of On DS RGCs correspond closely to differences in excitatory synaptic input the cells receive. Our results reveal a robust projection of On DS RGCs to the SC, projection-specific differences in the response properties of On DS RGCs, and biophysical and synaptic mechanisms that underlie these functional differences. PMID:25904807

  15. Vasoactive intestinal polypeptide: specific binding to rat brain membranes.

    PubMed Central

    Taylor, D P; Pert, C B

    1979-01-01

    The binding of radiolabeled vasoactive intestinal polypeptide (VIP) to rat brain membranes was investigated. Specific binding of 125I-labeled VIP was reversible and saturable (Bmax = 2.2 pmol/g of wet tissue). Brain membranes exhibited a high affinity for 125I-labeled VIP (KD = 1 nM) at a single class of noninteracting sites. Binding of 125I-labeled VIP paralleled its immunohistochemical localization, being enriched in cerebral cortex, hippocampus, striatum, and thalamus, with the notable exception of the hypothalamus, which had low levels of binding. The density of sites was greater in synaptosomal fractions relative to mitochondrial or nuclear fractions. Secretin and partial sequences of it and VIP inhibited binding to brain membranes with an order of potency similar to that found in other systems. The findings suggest the existence of a unique new class of brain receptors. PMID:218214

  16. Altered Resting Brain Function and Structure in Professional Badminton Players

    PubMed Central

    Di, Xin; Zhu, Senhua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan

    2012-01-01

    Abstract Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills. PMID:22840241

  17. Altered resting brain function and structure in professional badminton players.

    PubMed

    Di, Xin; Zhu, Senhua; Jin, Hua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan; Rao, Hengyi

    2012-01-01

    Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills. PMID:22840241

  18. Sialylation regulates brain structure and function.

    PubMed

    Yoo, Seung-Wan; Motari, Mary G; Susuki, Keiichiro; Prendergast, Jillian; Mountney, Andrea; Hurtado, Andres; Schnaar, Ronald L

    2015-07-01

    Every cell expresses a molecularly diverse surface glycan coat (glycocalyx) comprising its interface with its cellular environment. In vertebrates, the terminal sugars of the glycocalyx are often sialic acids, 9-carbon backbone anionic sugars implicated in intermolecular and intercellular interactions. The vertebrate brain is particularly enriched in sialic acid-containing glycolipids termed gangliosides. Human congenital disorders of ganglioside biosynthesis result in paraplegia, epilepsy, and intellectual disability. To better understand sialoglycan functions in the nervous system, we studied brain anatomy, histology, biochemistry, and behavior in mice with engineered mutations in St3gal2 and St3gal3, sialyltransferase genes responsible for terminal sialylation of gangliosides and some glycoproteins. St3gal2/3 double-null mice displayed dysmyelination marked by a 40% reduction in major myelin proteins, 30% fewer myelinated axons, a 33% decrease in myelin thickness, and molecular disruptions at nodes of Ranvier. In part, these changes may be due to dysregulation of ganglioside-mediated oligodendroglial precursor cell proliferation. Neuronal markers were also reduced up to 40%, and hippocampal neurons had smaller dendritic arbors. Young adult St3gal2/3 double-null mice displayed impaired motor coordination, disturbed gait, and profound cognitive disability. Comparisons among sialyltransferase mutant mice provide insights into the functional roles of brain gangliosides and sialoglycoproteins consistent with related human congenital disorders. PMID:25846372

  19. [Contribution of brain function analysis to the evolution of neurorehabilitation].

    PubMed

    Miyai, Ichiro; Mihara, Masahito; Hattori, Noriaki; Hatakenaka, Megumi; Kawano, Teiji; Yagura, Hajime

    2012-01-01

    Recent studies of functional neuroimaging and clinical neurophysiology have implied that functional recovery after stroke is associated with use-dependent plasticity of the damaged brain. However the property of the reorganized neural network depends on site and size of the lesion, which makes it difficult to assess what the adaptive plasticity is. From clinical point of view there is accumulating randomized controlled trials for the benefit of task-oriented rehabilitative intervention including constraint-induced movement therapy, robotics, and body-weight supported treadmill training. However dose-matched control intervention is usually as effective as a specific intervention. This raises a question regarding the specificity of a task-oriented intervention. Second question is whether such intervention goes beyond the biological destiny of human. Specifically there is no known strategy enhancing recovery of severely impaired hand. To augment functional gain, several methods of neuro-modulation may bring break-through on the assumption that they induce greater adaptive plasticity. Such neuro-modulative methods include neuropharmacological modulation, brain stimulation using transcranial magnetic stimulation and direct current stimulation, peripheral nerve stimulation, neurofeedback using real-time fMRI and real-time fNIRS, and brain-machine interface. A preliminary randomized controlled trial regarding real-time feedback of premotor activities revealed promising results for recovery of paretic hand in patients with stroke. PMID:23196554

  20. Clinton Woolsey: Functional Brain Mapping Pioneer

    PubMed Central

    Lyon, Will; Mehta, Tej I.; Pointer, Kelli B.; Walden, Daniel; Elmayan, Ardem; Swanson, Kyle I.; Kuo, John S.

    2014-01-01

    Dr. Clinton Woolsey was a leading twentieth century neuroscientist for almost four decades. His most significant achievements were the novel use and refinement of evoked potential techniques to functionally map mammalian brains, the discovery of secondary cortical areas, and a wide repertoire of comparative neurofunctional studies across many species. We discuss his life and work through a historical context with contemporaries, highlight the primitive state of brain mapping before Woolsey, and his involvement in advancing its rapid development through work at both Johns Hopkins University and University of Wisconsin in Madison. Dr. Woolsey’s lasting impact on basic and clinical neuroscience, neurosurgery, and neurology and his important roles as a scientific mentor and leader are also described. PMID:25105696

  1. Clinton Woolsey: functional brain mapping pioneer.

    PubMed

    Lyon, Will; Mehta, Tej I; Pointer, Kelli B; Walden, Daniel; Elmayan, Ardem; Swanson, Kyle I; Kuo, John S

    2014-10-01

    Dr. Clinton Woolsey was a leading 20th-century neuroscientist for almost 4 decades. His most significant achievements were the novel use and refinement of evoked potential techniques to functionally map mammalian brains, the discovery of secondary cortical areas, and a wide repertoire of comparative neurofunctional studies across many species. The authors discuss his life and work through a historical context with contemporaries, highlight the primitive state of brain mapping before Woolsey, and review his involvement in advancing its rapid development through work at both Johns Hopkins University and University of Wisconsin in Madison. Dr. Woolsey's lasting impact on basic and clinical neuroscience, neurosurgery, and neurology and his important roles as a scientific mentor and leader are also described. PMID:25105696

  2. The function of neurocognitive networks. Comment on “Understanding brain networks and brain organization” by Pessoa

    NASA Astrophysics Data System (ADS)

    Bressler, Steven L.

    2014-09-01

    Pessoa [5] has performed a valuable service by reviewing the extant literature on brain networks and making a number of interesting proposals about their cognitive function. The term function is at the core of understanding the brain networks of cognition, or neurocognitive networks (NCNs) [1]. The great Russian neuropsychologist, Luria [4], defined brain function as the common task executed by a distributed brain network of complex dynamic structures united by the demands of cognition. Casting Luria in a modern light, we can say that function emerges from the interactions of brain regions in NCNs as they dynamically self-organize according to cognitive demands. Pessoa rightly details the mapping between brain function and structure, emphasizing both its pluripotency (one structure having multiple functions) and degeneracy (many structures having the same function). However, he fails to consider the potential importance of a one-to-one mapping between NCNs and function. If NCNs are uniquely composed of specific collections of brain areas, then each NCN has a unique function determined by that composition.

  3. Dynamic reorganization of functional brain networks during picture naming.

    PubMed

    Hassan, Mahmoud; Benquet, Pascal; Biraben, Arnaud; Berrou, Claude; Dufor, Olivier; Wendling, Fabrice

    2015-12-01

    For efficient information processing during cognitive activity, functional brain networks have to rapidly and dynamically reorganize on a sub-second time scale. Tracking the spatiotemporal dynamics of large scale networks over this short time duration is a very challenging issue. Here, we tackle this problem by using dense electroencephalography (EEG) recorded during a picture naming task. We found that (i) the picture naming task can be divided into six brain network states (BNSs) characterized by significantly high synchronization of gamma (30-45 Hz) oscillations, (ii) fast transitions occur between these BNSs that last from 30 msec to 160 msec, (iii) based on the state of the art of the picture naming task, we consider that the spatial location of their nodes and edges, as well as the timing of transitions, indicate that each network can be associated with one or several specific function (from visual processing to articulation) and (iv) the comparison with previously-used approach aimed at localizing the sources showed that the network-based approach reveals networks that are more specific to the performed task. We speculate that the persistence of several brain regions in successive BNSs participates to fast and efficient information processing in the brain. PMID:26478964

  4. Functional Specificity of the Visual Word Form Area: General Activation for Words and Symbols but Specific Network Activation for Words

    ERIC Educational Resources Information Center

    Reinke, Karen; Fernandes, Myra; Schwindt, Graeme; O'Craven, Kathleen; Grady, Cheryl L.

    2008-01-01

    The functional specificity of the brain region known as the Visual Word Form Area (VWFA) was examined using fMRI. We explored whether this area serves a general role in processing symbolic stimuli, rather than being selective for the processing of words. Brain activity was measured during a visual 1-back task to English words, meaningful symbols

  5. Age- and brain region-specific differences in mitochondrial bioenergetics in Brown Norway rats.

    PubMed

    Pandya, Jignesh D; Royland, Joyce E; MacPhail, Robert C; Sullivan, Patrick G; Kodavanti, Prasada Rao S

    2016-06-01

    Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bioenergetic parameters in 5 brain regions (brain stem [BS], frontal cortex, cerebellum, striatum, hippocampus [HIP]) of 4 diverse age groups (1 month [young], 4 months [adult], 12 months [middle-aged], 24 months [old age]) to understand age-related differences in selected brain regions and their possible contribution to age-related chemical sensitivity. Mitochondrial bioenergetic parameters and enzyme activities were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5/group). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State III respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12, and 24-months age groups. Activities of mitochondrial pyruvate dehydrogenase complex and electron transport chain complexes I, II, and IV enzymes were also age and brain region specific. In general, changes associated with age were more pronounced with enzyme activities declining as the animals aged (young > adult > middle-aged > old age). These age- and brain region-specific observations may aid in evaluating brain bioenergetic impact on the age-related susceptibility to environmental chemical stressors. PMID:27143418

  6. A Bayesian model of category-specific emotional brain responses.

    PubMed

    Wager, Tor D; Kang, Jian; Johnson, Timothy D; Nichols, Thomas E; Satpute, Ajay B; Barrett, Lisa Feldman

    2015-04-01

    Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories--fear, anger, disgust, sadness, or happiness--is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490

  7. A Bayesian Model of Category-Specific Emotional Brain Responses

    PubMed Central

    Wager, Tor D.; Kang, Jian; Johnson, Timothy D.; Nichols, Thomas E.; Satpute, Ajay B.; Barrett, Lisa Feldman

    2015-01-01

    Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories—fear, anger, disgust, sadness, or happiness—is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490

  8. Brain Functional and Structural Predictors of Language Performance.

    PubMed

    Skeide, Michael A; Brauer, Jens; Friederici, Angela D

    2016-05-01

    The relation between brain function and behavior on the one hand and the relation between structural changes and behavior on the other as well as the link between the 2 aspects are core issues in cognitive neuroscience. It is an open question, however, whether brain function or brain structure is the better predictor for age-specific cognitive performance. Here, in a comprehensive set of analyses, we investigated the direct relation between hemodynamic activity in 2 pairs of frontal and temporal cortical areas, 2 long-distance white matter fiber tracts connecting each pair and sentence comprehension performance of 4 age groups, including 3 groups of children between 3 and 10 years as well as young adults. We show that the increasing accuracy of processing complex sentences throughout development is correlated with the blood-oxygen-level-dependent activation of 2 core language processing regions in Broca's area and the posterior portion of the superior temporal gyrus. Moreover, both accuracy and speed of processing are correlated with the maturational status of the arcuate fasciculus, that is, the dorsal white matter fiber bundle connecting these 2 regions. The present data provide compelling evidence for the view that brain function and white matter structure together best predict developing cognitive performance. PMID:25770126

  9. Split My Brain: A Case Study of Seizure Disorder and Brain Function

    ERIC Educational Resources Information Center

    Omarzu, Julia

    2004-01-01

    This case involves a couple deciding whether or not their son should undergo brain surgery to treat a severe seizure disorder. In examining this dilemma, students apply knowledge of brain anatomy and function. They also learn about brain scanning techniques and discuss the plasticity of the brain.

  10. The neuropathology of alcohol-specific brain damage, or does alcohol damage the brain?

    PubMed

    Harper, C

    1998-02-01

    The aim of this review is to identify neuropathological changes that are directly related to the long-term use of excessive amounts of alcohol (ethanol). There is still debate as to whether alcohol per se causes brain damage. The main problem has been to identify those lesions caused by alcohol itself and those caused by other common alcohol-related factors, principally thiamin deficiency. Careful selection and classification of alcoholic cases into those with and without these complications, together with detailed quantitative neuropathological analyses, has provided us with useful data. There is brain shrinkage in uncomplicated alcoholics which can largely be accounted for by loss of white matter. Some of this damage appears to be reversible. However, alcohol-related neuronal loss has been documented in specific regions of the cerebral cortex (superior frontal association cortex), hypothalamus (supraoptic and paraventricular nuclei), and cerebellum. The data is conflicting for several regions: the hippocampus, amygdala and locus ceruleus. No change is found in the basal ganglia, nucleus basalis, or serotonergic raphe nuclei. Many of the regions that are normal in uncomplicated alcoholics are damaged in those with the Wernicke-Korsakoff syndrome. Dendritic and synaptic changes have been documented in uncomplicated alcoholics and these, together with receptor and transmitter changes, may explain functional changes and cognitive deficits that precede the more severe structural neuronal changes. The pattern of damage appears to be somewhat different and species-specific in animal models of alcohol toxicity. Pathological changes that have been found to correlate with alcohol intake include white matter loss and neuronal loss in the hypothalamus and cerebellum. PMID:9600202

  11. Dynamic Functional Brain Connectivity for Face Perception

    PubMed Central

    Yang, Yuan; Qiu, Yihong; Schouten, Alfred C.

    2015-01-01

    Face perception is mediated by a distributed brain network comprised of the core system at occipito-temporal areas and the extended system at other relevant brain areas involving bilateral hemispheres. In this study we explored how the brain connectivity changes over the time for face-sensitive processing. We investigated the dynamic functional connectivity in face perception by analyzing time-dependent EEG phase synchronization in four different frequency bands: theta (4–7 Hz), alpha (8–14 Hz), beta (15–24 Hz), and gamma (25–45 Hz) bands in the early stages of face processing from 30 to 300 ms. High-density EEG were recorded from subjects who were passively viewing faces, buildings, and chairs. The dynamic connectivity within the core system and between the extended system were investigated. Significant differences between faces and non-faces mainly appear in theta band connectivity: (1) at the time segment of 90–120 ms between parietal area and occipito-temporal area in the right hemisphere, and (2) at the time segment of 150–180 ms between bilateral occipito-temporal areas. These results indicate (1) the importance of theta-band connectivity in the face-sensitive processing, and (2) that different parts of network are involved for the initial stage of face categorization and the stage of face structural encoding. PMID:26696870

  12. Brain Dynamics, Chaos and Bessel Functions

    NASA Astrophysics Data System (ADS)

    Freeman, W. J.; Capolupo, A.; Kozma, R.; Olivares del Campo, A.; Vitiello, G.

    2015-07-01

    By resorting to Freeman's observations showing that the distribution functions of impulse responses of cortex to sensory stimuli resemble Bessel functions, we study brain dynamics by considering the equivalence of spherical Bessel equation, in a given parametrization, to two oscillator equations, one damped and one amplified oscillator. The study of such a couple of equations, which are at the basis of the formulation of the dissipative many-body model, reveals the structure of the root loci of poles and zeros of solutions of Bessel equations, which are consistent with results obtained using ordinary differential equation techniques. We analyze stable and unstable limit cycles and consider thermodynamic features of brain functioning, which in this way may be described in terms of transitions between chaotic gas-like and ordered liquid-like behaviors. Nonlinearity dominates the dynamical critical transition regimes. Linear behavior, on the other hand, characterizes superpositions within self-organized neuronal domains in each dynamical phase. The formalism is consistent with the observed coexistence in circular causality of pulse density fields and wave density fields.

  13. The Construction of Common and Specific Significance Subnetworks of Alzheimer's Disease from Multiple Brain Regions

    PubMed Central

    Mou, Xiaoyang; Zhang, Na; Zeng, Weiming; Li, Shasha; Yang, Yang

    2015-01-01

    Alzheimer's disease (AD) is a progressively and fatally neurodegenerative disorder and leads to irreversibly cognitive and memorial damage in different brain regions. The identification and analysis of the dysregulated pathways and subnetworks among affected brain regions will provide deep insights for the pathogenetic mechanism of AD. In this paper, commonly and specifically significant subnetworks were identified from six AD brain regions. Protein-protein interaction (PPI) data were integrated to add molecular biological information to construct the functional modules of six AD brain regions by Heinz algorithm. Then, the simulated annealing algorithm based on edge weight is applied to predicting and optimizing the maximal scoring networks for common and specific genes, respectively, which can remove the weak interactions and add the prediction of strong interactions to increase the accuracy of the networks. The identified common subnetworks showed that inflammation of the brain nerves is one of the critical factors of AD and calcium imbalance may be a link among several causative factors in AD pathogenesis. In addition, the extracted specific subnetworks for each brain region revealed many biologically functional mechanisms to understand AD pathogenesis. PMID:25866779

  14. Studying newt brain regeneration following subtype specific neuronal ablation.

    PubMed

    Kirkham, Matthew; Joven, Alberto

    2015-01-01

    The realization that neuronal injury does not result in permanent functional or cellular loss in all vertebrates has fascinated regenerative biologists. Neuronal regeneration occurs in a subset of species, including lizards, teleost fish, axolotls, and newts. One tool for studying neuronal regeneration in the adult brain is intraventricular injection of selective neuronal toxins, which leads to loss of subpopulations of neurons. To trace cells involved in the regeneration process, plasmids encoding reporter proteins can be electroporated in vivo into the cells of interest. This protocol describes methods to label the ependymoglial cells of the brain of the red spotted newt Notophthalmus viridescens and follow their response after ablation of dopaminergic neurons. PMID:25740479

  15. 28 CFR 0.131 - Specific functions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Specific functions. 0.131 Section 0.131 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Bureau of Alcohol, Tobacco, Firearms, and Explosives § 0.131 Specific functions. The Director of the Bureau of...

  16. 28 CFR 0.131 - Specific functions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Specific functions. 0.131 Section 0.131 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Bureau of Alcohol, Tobacco, Firearms, and Explosives § 0.131 Specific functions. The Director of the Bureau of Alcohol, Tobacco, Firearms, and Explosives shall:...

  17. Site-specific opening of the blood-brain barrier

    PubMed Central

    Madsen, Steen J.; Hirschberg, Henry

    2014-01-01

    The blood-brain barrier (BBB) poses a significant impediment for the delivery of therapeutic drugs into the brain. This is particularly problematic for the treatment of malignant gliomas which are characterized by diffuse infiltration of tumor cells into normal brain where they are protected by a patent BBB. Selective disruption of the BBB, followed by administration of anti-cancer agents, represents a promising approach for the elimination of infiltrating glioma cells. A summary of the techniques (focused ultrasound, photodynamic therapy and photochemical internalization) for site-specific opening of the BBB will be discussed in this review. Each approach is capable of causing localized and transient opening of the BBB with minimal damage to surrounding normal brain as evidenced from magnetic resonance images and histology. T1-weighted MRI contrast enhanced images (a, b) showing focal enhancement in the area of light treatment. Fluence levels of 9 (a) and 17 J (b) at a fluence rate of 10 mW were performed 4 h following ALA administration (125 mg kg−1 i.p.). Scans were acquired 3–4 h post-PDT and 15 min following i.p. Gd contrast administration. Coronal H&E sections (c, d) taken from the brains of Fischer rats 14 days post-treatment. No significant pathology was observed following delivery of 9 J (c). At the high fluence (17 J), extensive infiltration of lymphocytes and macrophages was apparent as shown by the arrow in (d) [19]. Reprinted with permission. PMID:20162563

  18. Radial glial cell-specific ablation in the adult Zebrafish brain.

    PubMed

    Shimizu, Yuki; Ito, Yoko; Tanaka, Hideomi; Ohshima, Toshio

    2015-07-01

    The zebrafish brain can continue to produce new neurons in widespread neurogenic brain regions throughout life. In contrast, neurogenesis in the adult mammalian brain is restricted to the subventricular zone (SVZ) and dentate gyrus (DG). In neurogenic regions in the adult brain, radial glial cells (RGCs) are considered to function as neural stem cells (NSCs). We generated a Tg(gfap:Gal4FF) transgenic zebrafish line, which enabled us to express specific genes in RGCs. To study the function of RGCs in neurogenesis in the adult zebrafish brain, we also generated a Tg(gfap: Gal4FF; UAS:nfsB-mcherry) transgenic zebrafish line, which allowed us to induce cell death exclusively within RGCs upon addition of metronidazole (Mtz) to the media. RGCs expressing nitroreductase were specifically ablated by the Mtz treatment, decreasing the number of proliferative RGCs. Using the Tg(gfap:Gal4FF; UAS:nfsB-mcherry) transgenic zebrafish line, we found that RGCs were specifically ablated in the adult zebrafish telencephalon. The Tg(gfap:Gal4FF) line could be useful to study the function of RGCs. PMID:26045148

  19. Phosphatidylserine in the Brain: Metabolism and Function

    PubMed Central

    Kim, Hee-Yong; Huang, Bill X.; Spector, Arthur A.

    2014-01-01

    Phosphatidylserine (PS) is the major anionic phospholipid class particularly enriched in the inner leaflet of the plasma membrane in neural tissues. PS is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine in reactions are catalyzed by phosphatidylserine synthase 1 and phosphatidylserine synthase 2 located in the endoplasmic reticulum. Activation of Akt, Raf-1 and protein kinase C signaling, which supports neuronal survival and differentiation, requires interaction of these proteins with PS localized in the cytoplasmic leaflet of the plasma membrane. Furthermore, neurotransmitter release by exocytosis and a number of synaptic receptors and proteins are modulated by PS present in the neuronal membranes. Brain is highly enriched with docosahexaenoic acid (DHA), and brain PS has a high DHA content. By promoting PS synthesis, DHA can uniquely expand the PS pool in neuronal membranes and thereby influence PS-dependent signaling and protein function. Ethanol decreases DHA-promoted PS synthesis and accumulation in neurons, which may contribute to the deleterious effects of ethanol intake. Improvement of some memory functions has been observed in cognitively impaired subjects as a result of PS supplementation, but the mechanism is unclear. PMID:24992464

  20. Age-Related Reorganizational Changes in Modularity and Functional Connectivity of Human Brain Networks

    PubMed Central

    Song, Jie; Birn, Rasmus M.; Boly, Mélanie; Meier, Timothy B.; Nair, Veena A.; Prabhakaran, Vivek

    2014-01-01

    Abstract The human brain undergoes both morphological and functional modifications across the human lifespan. It is important to understand the aspects of brain reorganization that are critical in normal aging. To address this question, one approach is to investigate age-related topological changes of the brain. In this study, we developed a brain network model using graph theory methods applied to the resting-state functional magnetic resonance imaging data acquired from two groups of normal healthy adults classified by age. We found that brain functional networks demonstrated modular organization in both groups with modularity decreased with aging, suggesting less distinct functional divisions across whole brain networks. Local efficiency was also decreased with aging but not with global efficiency. Besides these brain-wide observations, we also observed consistent alterations of network properties at the regional level in the elderly, particularly in two major functional networks—the default mode network (DMN) and the sensorimotor network. Specifically, we found that measures of regional strength, local and global efficiency of functional connectivity were increased in the sensorimotor network while decreased in the DMN with aging. These results indicate that global reorganization of brain functional networks may reflect overall topological changes with aging and that aging likely alters individual brain networks differently depending on the functional properties. Moreover, these findings highly correspond to the observation of decline in cognitive functions but maintenance of primary information processing in normal healthy aging, implying an underlying compensation mechanism evolving with aging to support higher-level cognitive functioning. PMID:25183440

  1. Early Brain Stimulation May Help Stroke Survivors Recover Language Function

    MedlinePlus

    ... Media Hub On Heart.org Learn More Early brain stimulation may help stroke survivors recover language function ... and strokeassociation.org Share Related Images Infographic - Thiel-Brain Stimulation copyright American Heart Association Download (311.8 ...

  2. Dietary boron, brain function, and cognitive performance.

    PubMed Central

    Penland, J G

    1994-01-01

    Although the trace element boron has yet to be recognized as an essential nutrient for humans, recent data from animal and human studies suggest that boron may be important for mineral metabolism and membrane function. To investigate further the functional role of boron, brain electrophysiology and cognitive performance were assessed in response to dietary manipulation of boron (approximately 0.25 versus approximately 3.25 mg boron/2000 kcal/day) in three studies with healthy older men and women. Within-subject designs were used to assess functional responses in all studies. Spectral analysis of electroencephalographic data showed effects of dietary boron in two of the three studies. When the low boron intake was compared to the high intake, there was a significant (p < 0.05) increase in the proportion of low-frequency activity, and a decrease in the proportion of higher-frequency activity, an effect often observed in response to general malnutrition and heavy metal toxicity. Performance (e.g., response time) on various cognitive and psychomotor tasks also showed an effect of dietary boron. When contrasted with the high boron intake, low dietary boron resulted in significantly poorer performance (p < 0.05) on tasks emphasizing manual dexterity (studies II and III); eye-hand coordination (study II); attention (all studies); perception (study III); encoding and short-term memory (all studies); and long-term memory (study I). Collectively, the data from these three studies indicate that boron may play a role in human brain function and cognitive performance, and provide additional evidence that boron is an essential nutrient for humans. PMID:7889884

  3. Order and disorder in the brain function.

    PubMed

    Quadens, Olga

    2003-01-01

    The interest in studying the brain electrical activity as a function of the development of intelligence has been spurred by the need to understand how the brain responds to environmental information. The description of sleep in mentally retarded children reveals deviant patterns of the EEG-spindles and of the eye movement activity (REM sleep) when compared to normal children. The patterns may be considered as a valuable index of mental function. According to experimental evidence, the distribution of the eye movements of sleep appears either as random or ordered. The latter are altered in the mentally handicapped in whom the appearance out of chaos, of the order which is needed for intelligence and memory to function, is altered. The sleep signs are redundant as from birth. Their pattern is also related to the psychomotor development of the infant. If their distribution remains random, or appears in long uninterrupted sequences of waves as in epilepsy, intelligence does not develop. A similar strategy appears to function in the foetus when nature organizes the structures that will lead to the development of intelligence. The eye movement patterns of sleep change in the pregnant women as a function of term and resemble those of premature babies of a similar gestational age. They also change as a function of the menstrual cycle and more generally as a function of age. The hypothesis that attention is the diurnal equivalent of REM sleep is discussed. Attempts at modelling the eye movement patterns of REM sleep as a function of near zero gravity environments have been made. 1) By means of a Montecarlo simulation using the semi Markov model during the Spacelab 1 flight. 2) With the method of the single and multiple g-phase transition analysis of the strange attractor dimension (d) during parabolic flights. The implication of the latter for the neural processes involved in learning is that the central nervous system can preserve intact, from input to output, over a period of several days, all the information it receives 3) The relation between spindles and eye movements has also been viewed by a quantum approach which is another medium between the information and the way of describing it. PMID:14523349

  4. ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS

    PubMed Central

    Bredel, Markus; Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; Elverfeldt, Dominik v.; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.

    2014-01-01

    BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR. CONCLUSIONS: Our data illustrate how anomalous splicing of a tissue-regulated exon in a constituent of an oncogenic signaling pathway eliminates its tumor suppressor function and promotes tumorigenesis. This paradigm of malignant glial transformation as a consequence of tissue-specific alternative exon splicing in a tumor suppressor, may have widespread applicability in explaining how changes in critical tissue-specific regulatory mechanisms reprogram normal development to oncogenesis. SECONDARY CATEGORY: n/a.

  5. Altered Small-World Efficiency of Brain Functional Networks in Acupuncture at ST36: A Functional MRI Study

    PubMed Central

    Liu, Xian; Duan, Xiaohui; Shang, Xiaojing; Long, Yu; Chen, Zhiguang; Li, Xiaofang; Huang, Yan; He, Yong

    2012-01-01

    Background Acupuncture in humans can produce clinical effects via the central nervous system. However, the neural substrates of acupuncture’s effects remain largely unknown. Results We utilized functional MRI to investigate the topological efficiency of brain functional networks in eighteen healthy young adults who were scanned before and after acupuncture at the ST36 acupoints (ACUP) and its sham point (SHAM). Whole-brain functional networks were constructed by thresholding temporal correlations matrices of ninety brain regions, followed by a graph theory-based analysis. We showed that brain functional networks exhibited small-world attributes (high local and global efficiency) regardless of the order of acupuncture and stimulus points, a finding compatible with previous studies of brain functional networks. Furthermore, the brain networks had increased local efficiency after ACUP stimulation but there were no significant differences after SHAM, indicating a specificity of acupuncture point in coordinating local information flow over the whole brain. Moreover, significant (P<0.05, corrected by false discovery rate approach) effects of only acupuncture point were detected on nodal degree of the left hippocampus (higher nodal degree at ACUP as compared to SHAM). Using an uncorrected P<0.05, point-related effects were also observed in the anterior cingulate cortex, frontal and occipital regions while stimulation-related effects in various brain regions of frontal, parietal and occipital cortex regions. In addition, we found that several limbic and subcortical brain regions exhibited point- and stimulation-related alterations in their regional homogeneity (P<0.05, uncorrected). Conclusions Our results suggest that acupuncture modulates topological organization of whole-brain functional brain networks and the modulation has point specificity. These findings provide new insights into neuronal mechanism of acupuncture from the perspective of functional integration. Further studies would be interesting to apply network analysis approaches to study the effects of acupuncture treatments on brain disorders. PMID:22761766

  6. Cell type-specific transcriptome profiling in mammalian brains.

    PubMed

    LoVerso, Peter R; Cui, Feng

    2016-01-01

    A mammalian brain contains numerous types of cells. Advances in neuroscience in the past decade allow us to identify and isolate neural cells of interest from mammalian brains. Recent developments in high-throughput technologies, such as microarrays and next-generation sequencing (NGS), provide detailed information on gene expression in pooled cells on a genomic scale. As a result, many novel genes have been found critical in cell type-specific transcriptional regulation. These differentially expressed genes can be used as molecular signatures, unique to a particular class of neural cells. Use of this gene expression-based approach can further differentiate neural cell types into subtypes, potentially linking some of them with neurological diseases. In this article, experimental techniques used to purify neural cells are described, followed by a review on recent microarray- or NGS-based transcriptomic studies of common neural cell types. The future prospects of cell type-specific research are also discussed. PMID:27100485

  7. Cell type-specific gene expression profiling in brain tissue: comparison between TRAP, LCM and RNA-seq

    PubMed Central

    Kim, TaeHyun; Lim, Chae-Seok; Kaang, Bong-Kiun

    2015-01-01

    The brain is an organ that consists of various cell types. As our knowledge of the structure and function of the brain progresses, cell type-specific research is gaining importance. Together with advances in sequencing technology and bioinformatics, cell type-specific transcriptome studies are providing important insights into brain cell function. In this review, we discuss 3 different cell type-specific transcriptome analyses i.e., Laser Capture Microdissection (LCM), Translating Ribosome Affinity Purification (TRAP)/RiboTag, and single cell RNA-Seq, that are widely used in the field of neuroscience. [BMB Reports 2015; 48(7): 388-394] PMID:25603796

  8. Integrating in vitro organ-specific function with the microcirculation

    PubMed Central

    Moya, Monica L.; George, Steven C.

    2014-01-01

    There is significant interest within the tissue engineering and pharmaceutical industries to create 3D microphysiological systems of human organ function. The interest stems from a growing concern that animal models and simple 2D culture systems cannot replicate essential features of human physiology that are critical to predict drug response, or simply to develop new therapeutic strategies to repair or replace damaged organs. Central to human organ function is a microcirculation that not only enhances the rate of nutrient and waste transport by convection, but also provides essential additional physiological functions that can be specific to each organ. This review highlights progress in the creation of in vitro functional microvessel networks, and emphasizes organ-specific functional and structural characteristics that should be considered in the future mimicry of four organ systems that are of primary interest: lung, brain, liver, and muscle (skeletal and cardiac). PMID:24729953

  9. Brain microvascular function during cardiopulmonary bypass

    SciTech Connect

    Sorensen, H.R.; Husum, B.; Waaben, J.; Andersen, K.; Andersen, L.I.; Gefke, K.; Kaarsen, A.L.; Gjedde, A.

    1987-11-01

    Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracers being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass.

  10. Predicting individual brain maturity using dynamic functional connectivity

    PubMed Central

    Qin, Jian; Chen, Shan-Guang; Hu, Dewen; Zeng, Ling-Li; Fan, Yi-Ming; Chen, Xiao-Ping; Shen, Hui

    2015-01-01

    Neuroimaging-based functional connectivity (FC) analyses have revealed significant developmental trends in specific intrinsic connectivity networks linked to cognitive and behavioral maturation. However, knowledge of how brain functional maturation is associated with FC dynamics at rest is limited. Here, we examined age-related differences in the temporal variability of FC dynamics with data publicly released by the Nathan Kline Institute (NKI; n = 183, ages 7–30) and showed that dynamic inter-region interactions can be used to accurately predict individual brain maturity across development. Furthermore, we identified a significant age-dependent trend underlying dynamic inter-network FC, including increasing variability of the connections between the visual network, default mode network (DMN) and cerebellum as well as within the cerebellum and DMN and decreasing variability within the cerebellum and between the cerebellum and DMN as well as the cingulo-opercular network. Overall, the results suggested significant developmental changes in dynamic inter-network interaction, which may shed new light on the functional organization of typical developmental brains. PMID:26236224

  11. Consistency and functional specialization in the default mode brain network.

    PubMed

    Harrison, Ben J; Pujol, Jesus; López-Solà, Marina; Hernández-Ribas, Rosa; Deus, Joan; Ortiz, Hector; Soriano-Mas, Carles; Yücel, Murat; Pantelis, Christos; Cardoner, Narcís

    2008-07-15

    The notion of a "default mode of brain function" has taken on certain relevance in human neuroimaging studies and in relation to a network of lateral parietal and midline cortical regions that show prominent activity fluctuations during passive imaging states, such as rest. In this study, we perform three fMRI experiments that demonstrate consistency and specialization in the default mode network. Correlated activity fluctuations of default mode network regions are identified during (i) eyes-closed spontaneous rest, (ii) activation by moral dilemma, and (iii) deactivation by Stroop task performance. Across these imaging states, striking uniformity is shown in the basic anatomy of the default mode network, but with both tasks clearly and differentially modulating this activity compared with spontaneous fluctuations of the network at rest. Against rest, moral dilemma is further shown to evoke regionally specific activity increases of hypothesized functional relevance. Mapping spontaneous and task-related brain activity will help to constrain the meaning of the default mode network. These findings are discussed in relation to recent debate on the topic of default modes of brain function. PMID:18621692

  12. Data-driven analysis of functional brain interactions during free listening to music and speech.

    PubMed

    Fang, Jun; Hu, Xintao; Han, Junwei; Jiang, Xi; Zhu, Dajiang; Guo, Lei; Liu, Tianming

    2015-06-01

    Natural stimulus functional magnetic resonance imaging (N-fMRI) such as fMRI acquired when participants were watching video streams or listening to audio streams has been increasingly used to investigate functional mechanisms of the human brain in recent years. One of the fundamental challenges in functional brain mapping based on N-fMRI is to model the brain's functional responses to continuous, naturalistic and dynamic natural stimuli. To address this challenge, in this paper we present a data-driven approach to exploring functional interactions in the human brain during free listening to music and speech streams. Specifically, we model the brain responses using N-fMRI by measuring the functional interactions on large-scale brain networks with intrinsically established structural correspondence, and perform music and speech classification tasks to guide the systematic identification of consistent and discriminative functional interactions when multiple subjects were listening music and speech in multiple categories. The underlying premise is that the functional interactions derived from N-fMRI data of multiple subjects should exhibit both consistency and discriminability. Our experimental results show that a variety of brain systems including attention, memory, auditory/language, emotion, and action networks are among the most relevant brain systems involved in classic music, pop music and speech differentiation. Our study provides an alternative approach to investigating the human brain's mechanism in comprehension of complex natural music and speech. PMID:24526569

  13. Effects of the diet on brain function

    NASA Technical Reports Server (NTRS)

    Fernstrom, J. D.

    1981-01-01

    The rates of synthesis by brain neurons of the neurotransmitters serotonin, acetylcholine, and the catecholamines depend on the brain levels of the respective precursor molecules. Brain levels of each precursor are influenced by their blood concentration, and for the amino acid precursors, by the blood levels of other amino acids as well. Since diet readily alters blood concentrations of each of these precursors, it thereby also influences the brain formation of their neutrotransmitter products.

  14. Interaction of functionalized superparamagnetic iron oxide nanoparticles with brain structures.

    PubMed

    Cengelli, Feride; Maysinger, Dusica; Tschudi-Monnet, Florianne; Montet, Xavier; Corot, Claire; Petri-Fink, Alke; Hofmann, Heinrich; Juillerat-Jeanneret, Lucienne

    2006-07-01

    Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) combined with magnetic resonance imaging (MRI) are under clinical evaluation to enhance detection of neurodegenerative diseases. A major improvement would be to link therapeutic drugs to the SPIONs to achieve targeted drug delivery, either at the cell surface or intracellularly, together with active disease detection, without inducing cell reaction. Our objectives were to define the characteristics of SPIONS able to achieve cell-specific interaction with brain-derived structures. Our system consisted in an iron oxide core (9-10 nm diameter) coated either with dextran (Sinerem and Endorem) or various functionalized polyvinyl alcohols (PVAs) (PVA-SPIONs). We investigated the cellular uptake, cytotoxicity, and interaction of these various nanoparticles with brain-derived endothelial cells, microglial cells, and differentiating three-dimensional aggregates. None of the nanoparticles coated with dextran or the various PVAs was cytotoxic or induced the production of the inflammatory mediator NO used as a reporter for cell activation. AminoPVA-SPIONs were taken up by isolated brain-derived endothelial and microglial cells at a much higher level than the other SPIONs, and no inflammatory activation of these cells was observed. AminoPVA-SPIONs did not invade brain cells aggregates lower than the first cell layer and did not induce inflammatory reaction in the aggregates. Fluorescent aminoPVA-SPIONs derivatized with a fluorescent reporter molecule and confocal microscopy demonstrated intracellular uptake by microglial cells. Fluorescent aminoPVA-SPIONs were well tolerated by mice. Therefore, functionalized aminoPVA-SPIONs represent biocompatible potential vector systems for drug delivery to the brain that may be combined with MRI detection of active lesions in neurodegenerative diseases. PMID:16608917

  15. Neuropsychological functioning of children with brain tumors.

    PubMed

    Divcić, Branka; Hajnzić, Tomislav Franjo

    2008-06-01

    In the past few decades, the survivor rate from childhood cancers has significantly increased due to constant modifications and improvements in treatment protocols, so the estimates are that childhood cancer occurs in 1 per 600 children, and that 1 per 450 adolescents or young adults is a long-term cancer survivor. Nevertheless, radiation treatment is still a necessary option that certainly contributes to greater survival rate (75%), until new approaches to patients with malignant diseases are accepted. In our clinical practice, surgical treatment for malignant brain tumor is followed by radio- and chemotherapy tailored according to patient age and tumor type, position and size. During a six-year period, neuropsychological functioning was tested in 21 patients upon completion of treatment and retested in 19 patients in the stage of primary disease remission. Comparison of the test-retest results revealed some, statistically nonsignificant decline in full scale IQ, verbal and performance subscales, and graphomotor skills. However, the results showed a statistically significant improvement in several cognitive functions including short-term memory, information fund (suggesting long-term memory improvement), visuospatial functions measured by object assemble and block design subtests. There were no statistically significant differences between the patients younger and older than 7 years. Results also suggested an improved quality of recovery expressed by numerous school re-entries, without age or sex differences. Trials are continued to follow-up the possible long -term adverse effects of the aggressive oncologic therapy. PMID:18949900

  16. 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 etiology at the cellular and circuit levels. PMID:26578866

  17. Mapping distributed brain function and networks with diffuse optical tomography

    NASA Astrophysics Data System (ADS)

    Eggebrecht, Adam T.; Ferradal, Silvina L.; Robichaux-Viehoever, Amy; Hassanpour, Mahlega S.; Dehghani, Hamid; Snyder, Abraham Z.; Hershey, Tamara; Culver, Joseph P.

    2014-06-01

    Mapping of human brain function has revolutionized systems neuroscience. However, traditional functional neuroimaging by positron emission tomography or functional magnetic resonance imaging cannot be used when applications require portability, or are contraindicated because of ionizing radiation (positron emission tomography) or implanted metal (functional magnetic resonance imaging). Optical neuroimaging offers a non-invasive alternative that is radiation free and compatible with implanted metal and electronic devices (for example, pacemakers). However, optical imaging technology has heretofore lacked the combination of spatial resolution and wide field of view sufficient to map distributed brain functions. Here, we present a high-density diffuse optical tomography imaging array that can map higher-order, distributed brain function. The system was tested by imaging four hierarchical language tasks and multiple resting-state networks including the dorsal attention and default mode networks. Finally, we imaged brain function in patients with Parkinson's disease and implanted deep brain stimulators that preclude functional magnetic resonance imaging.

  18. Heart and brain interconnection - clinical implications of changes in brain function during heart failure.

    PubMed

    Kim, Min-Seok; Kim, Jae-Joong

    2015-01-01

    Heart failure (HF) is a highly prevalent disorder worldwide and, consequently, a burden on the healthcare systems of many nations. Although the effects of HF are systemic, many therapeutic targets are focused on cardiac dysfunction. The brain is closely related to the heart, but there are few reports on the relationship between these organs. We describe the effects of the brain on HF progression. Specific brain regions control sympathetic drive and neurohumoral factors, which play an important role in disease exacerbation. In addition, we review some of our previous studies on deranged cerebral metabolism and reduced cerebral blood flow during HF. Although the reasons underlying these effects during HF remain uncertain, we propose plausible mechanisms for these phenomena. In addition, the clinical implications of such conditions in terms of predicting prognosis are discussed. Finally, we investigate cognitive impairment in patients with HF. Cognitive impairment through cerebral infarction or hypoperfusion is associated with adverse outcomes, including death. This brief review of brain function during the development of HF should assist with future strategies to better manage patients with this condition. PMID:25891994

  19. Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks.

    PubMed

    Michaelides, Michael; Anderson, Sarah Ann R; Ananth, Mala; Smirnov, Denis; Thanos, Panayotis K; Neumaier, John F; Wang, Gene-Jack; Volkow, Nora D; Hurd, Yasmin L

    2013-12-01

    The ability to map the functional connectivity of discrete cell types in the intact mammalian brain during behavior is crucial for advancing our understanding of brain function in normal and disease states. We combined designer receptor exclusively activated by designer drug (DREADD) technology and behavioral imaging with μPET and [18F]fluorodeoxyglucose (FDG) to generate whole-brain metabolic maps of cell-specific functional circuits during the awake, freely moving state. We have termed this approach DREADD-assisted metabolic mapping (DREAMM) and documented its ability in rats to map whole-brain functional anatomy. We applied this strategy to evaluating changes in the brain associated with inhibition of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) of the nucleus accumbens shell (NAcSh), which have been implicated in neuropsychiatric disorders. DREAMM revealed discrete behavioral manifestations and concurrent engagement of distinct corticolimbic networks associated with dysregulation of Pdyn and Penk in MSNs of the NAcSh. Furthermore, distinct neuronal networks were recruited in awake versus anesthetized conditions. These data demonstrate that DREAMM is a highly sensitive, molecular, high-resolution quantitative imaging approach. PMID:24231358

  20. Brain imaging and cognitive neuroscience. Toward strong inference in attributing function to structure.

    PubMed

    Sarter, M; Berntson, G G; Cacioppo, J T

    1996-01-01

    Cognitive neuroscience has emerged from the neurosciences and cognitive psychology as a scientific discipline that aims at the determination of "how brain function gives rise to mental activity" (S. M. Kosslyn & L. M. Shin, 1992, p. 146). While research in cognitive neuroscience combines many levels of neuroscientific and psychological analyses, modern imaging techniques that monitor brain activity during behavioral or cognitive operations have significantly contributed to the emergence of this discipline. The conclusions deduced from these studies are inherently localizationistic in nature; in other words, they describe cognitive functions as being localized in focal brain regions (brain activity in a defined brain region, phi, is involved in specific cognitive function, psi). A broad discussion about the virtues and limitations of such conclusions may help avoid the emergence of a mentalistic localizationism (i.e., the attribution of mentalistic concepts such as happiness, morality, or consciousness to brain structure) and illustrates the importance of a convergence with information generated by different research strategies (such as, for example, evidence generated by studies in which the effects of experimental manipulations of local neuronal processes on cognitive functions are assessed). Progress in capitalizing on brain-imaging studies to investigate questions of the form "brain structure or event phi is associated with cognitive function psi" may be impeded because of the way in which inferences are typically formulated in the brain imaging literature. A conceptual framework to advance the interpretation of data describing the relationships between cognitive phenomena and brain structure activity is provided. PMID:8585670

  1. Stimulation of functional vision in children with perinatal brain damage.

    PubMed

    Alimovi?, Sonja; Mejaski-Bosnjak, Vlatka

    2011-01-01

    Cerebral visual impairment (CVI) is one of the most common causes of bilateral visual loss, which frequently occurs due to perinatal brain injury. Vision in early life has great impact on acquisition of basic comprehensions which are fundamental for further development. Therefore, early detection of visual problems and early intervention is necessary. The aim of the present study is to determine specific visual functioning of children with perinatal brain damage and the influence of visual stimulation on development of functional vision at early age of life. We initially assessed 30 children with perinatal brain damage up to 3 years of age, who were reffered to our pediatric low vision cabinet in "Little house" from child neurologists, ophthalmologists Type and degree of visual impairment was determined according to functional vision assessment of each child. On the bases of those assessments different kind of visual stimulations were carried out with children who have been identified to have a certain visual impairment. Through visual stimulation program some of the children were stimulated with light stimulus, some with different materials under the ultraviolet (UV) light, and some with bright color and high contrast materials. Children were also involved in program of early stimulation of overall sensory motor development. Goals and methods of therapy were determined individually, based on observation of child's possibilities and need. After one year of program, reassessment was done. Results for visual functions and functional vision were compared to evaluate the improvement of the vision development. These results have shown that there was significant improvement in functional vision, especially in visual attention and visual communication. PMID:21648304

  2. BrainKnowledge: a human brain function mapping knowledge-base system.

    PubMed

    Hsiao, Mei-Yu; Chen, Chien-Chung; Chen, Jyh-Horng

    2011-03-01

    Associating fMRI image datasets with the available literature is crucial for the analysis and interpretation of fMRI data. Here, we present a human brain function mapping knowledge-base system (BrainKnowledge) that associates fMRI data analysis and literature search functions. BrainKnowledge not only contains indexed literature, but also provides the ability to compare experimental data with those derived from the literature. BrainKnowledge provides three major functions: (1) to search for brain activation models by selecting a particular brain function; (2) to query functions by brain structure; (3) to compare the fMRI data with data extracted from the literature. All these functions are based on our literature extraction and mining module developed earlier (Hsiao, Chen, Chen. Journal of Biomedical Informatics 42, 912-922, 2009), which automatically downloads and extracts information from a vast amount of fMRI literature and generates co-occurrence models and brain association patterns to illustrate the relevance of brain structures and functions. BrainKnowledge currently provides three co-occurrence models: (1) a structure-to-function co-occurrence model; (2) a function-to-structure co-occurrence model; and (3) a brain structure co-occurrence model. Each model has been generated from over 15,000 extracted Medline abstracts. In this study, we illustrate the capabilities of BrainKnowledge and provide an application example with the studies of affect. BrainKnowledge, which combines fMRI experimental results with Medline abstracts, may be of great assistance to scientists not only by freeing up resources and valuable time, but also by providing a powerful tool that collects and organizes over ten thousand abstracts into readily usable and relevant sources of information for researchers. PMID:20857233

  3. Topographic Brain Mapping: A Window on Brain Function?

    ERIC Educational Resources Information Center

    Karniski, Walt M.

    1989-01-01

    The article reviews the method of topographic mapping of the brain's electrical activity. Multiple electroencephalogram (EEG) electrodes and computerized analysis of the EEG signal are used to generate maps of frequency and voltage (evoked potential). This relatively new technique holds promise in the evaluation of children with behavioral and…

  4. The modular and integrative functional architecture of the human brain.

    PubMed

    Bertolero, Maxwell A; Yeo, B T Thomas; D'Esposito, Mark

    2015-12-01

    Network-based analyses of brain imaging data consistently reveal distinct modules and connector nodes with diverse global connectivity across the modules. How discrete the functions of modules are, how dependent the computational load of each module is to the other modules' processing, and what the precise role of connector nodes is for between-module communication remains underspecified. Here, we use a network model of the brain derived from resting-state functional MRI (rs-fMRI) data and investigate the modular functional architecture of the human brain by analyzing activity at different types of nodes in the network across 9,208 experiments of 77 cognitive tasks in the BrainMap database. Using an author-topic model of cognitive functions, we find a strong spatial correspondence between the cognitive functions and the network's modules, suggesting that each module performs a discrete cognitive function. Crucially, activity at local nodes within the modules does not increase in tasks that require more cognitive functions, demonstrating the autonomy of modules' functions. However, connector nodes do exhibit increased activity when more cognitive functions are engaged in a task. Moreover, connector nodes are located where brain activity is associated with many different cognitive functions. Connector nodes potentially play a role in between-module communication that maintains the modular function of the brain. Together, these findings provide a network account of the brain's modular yet integrated implementation of cognitive functions. PMID:26598686

  5. Infrared Imaging System for Studying Brain Function

    NASA Technical Reports Server (NTRS)

    Mintz, Frederick; Mintz, Frederick; Gunapala, Sarath

    2007-01-01

    A proposed special-purpose infrared imaging system would be a compact, portable, less-expensive alternative to functional magnetic resonance imaging (fMRI) systems heretofore used to study brain function. Whereas a typical fMRI system fills a large room, and must be magnetically isolated, this system would fit into a bicycle helmet. The system would include an assembly that would be mounted inside the padding in a modified bicycle helmet or other suitable headgear. The assembly would include newly designed infrared photodetectors and data-acquisition circuits on integrated-circuit chips on low-thermal-conductivity supports in evacuated housings (see figure) arranged in multiple rows and columns that would define image coordinates. Each housing would be spring-loaded against the wearer s head. The chips would be cooled by a small Stirling Engine mounted contiguous to, but thermally isolated from, the portions of the assembly in thermal contact with the wearer s head. Flexible wires or cables for transmitting data from the aforementioned chips would be routed to an integrated, multichannel transmitter and thence through the top of the assembly to a patch antenna on the outside of the helmet. The multiple streams of data from the infrared-detector chips would be sent to a remote site, where they would be processed, by software, into a three-dimensional display of evoked potentials that would represent firing neuronal bundles and thereby indicate locations of neuronal activity associated with mental or physical activity. The 3D images will be analogous to current fMRI images. The data would also be made available, in real-time, for comparison with data in local or internationally accessible relational databases that already exist in universities and research centers. Hence, this system could be used in research on, and for the diagnosis of response from the wearer s brain to physiological, psychological, and environmental changes in real time. The images would also be stored in a relational database for comparison with corresponding responses previously observed in other subjects.

  6. Brain serotonin and pituitary-adrenal functions

    NASA Technical Reports Server (NTRS)

    Vernikos-Danellis, J.; Berger, P.; Barchas, J. D.

    1973-01-01

    It had been concluded by Scapagnini et al. (1971) that brain serotonin (5-HT) was involved in the regulation of the diurnal rhythm of the pituitary-adrenal system but not in the stress response. A study was conducted to investigate these findings further by evaluating the effects of altering brain 5-HT levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. In a number of experiments brain 5-HT synthesis was inhibited with parachlorophenylalanine. In other tests it was tried to raise the level of brain 5-HT with precursors.

  7. Imaging structural and functional brain networks in temporal lobe epilepsy

    PubMed Central

    Bernhardt, Boris C.; Hong, SeokJun; Bernasconi, Andrea; Bernasconi, Neda

    2013-01-01

    Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy. PMID:24098281

  8. Gut microbial communities modulating brain development and function

    PubMed Central

    Al-Asmakh, Maha; Anuar, Farhana; Zadjali, Fahad; Rafter, Joseph; Pettersson, Sven

    2012-01-01

    Mammalian brain development is initiated in utero and internal and external environmental signals can affect this process all the way until adulthood. Recent observations suggest that one such external cue is the indigenous microbiota which has been shown to affect developmental programming of the brain. This may have consequences for brain maturation and function that impact on cognitive functions later in life. This review discusses these recent findings from a developmental perspective. PMID:22743758

  9. Laser technique for anatomical-functional study of the medial prefrontal cortex of the brain

    NASA Astrophysics Data System (ADS)

    Sanchez-Huerta, Laura; Hernandez, Adan; Ayala, Griselda; Marroquin, Javier; Silva, Adriana B.; Khotiaintsev, Konstantin S.; Svirid, Vladimir A.; Flores, Gonzalo; Khotiaintsev, Sergei N.

    1999-05-01

    The brain represents one of the most complex systems that we know yet. In its study, non-destructive methods -- in particular, behavioral studies play an important role. By alteration of brain functioning (e.g. by pharmacological means) and observation of consequent behavior changes an important information on brain organization and functioning is obtained. For inducing local alterations, permanent brain lesions are employed. However, for correct results this technique has to be quasi-non-destructive, i.e. not to affect the normal brain function. Hence, the lesions should be very small, accurate and applied precisely over the structure (e.g. the brain nucleus) of interest. These specifications are difficult to meet with the existing techniques for brain lesions -- specifically, neurotoxical, mechanical and electrical means because they result in too extensive damage. In this paper, we present new laser technique for quasi-non- destructive anatomical-functional mapping in vivo of the medial prefrontal cortex (MPFC) of the rat. The technique is based on producing of small-size, well-controlled laser- induced lesions over some areas of the MPFC. The anesthetized animals are subjected to stereotactic surgery and certain points of the MPFC are exposed the confined radiation of the 10 W cw CO2 laser. Subsequent behavioral changes observed in neonatal and adult animals as well as histological data prove effectiveness of this technology for anatomical- functional studies of the brain by areas, and as a treatment method for some pathologies.

  10. Brain Research: The Necessity for Separating Sites, Actions and Functions.

    ERIC Educational Resources Information Center

    Meeker, Mary

    Educators, as applied scientists, must work in partnership with investigative scientists who are researching brain functions in order to reach a better understanding of gifted students and students who are intelligent but do not learn. Improper understanding of brain functions can cause gross errors in educational placement. Until recently, the…

  11. [Functional organization of a photoperiodic brain system].

    PubMed

    Zamorskiĭ, I I; Pishak, V P

    2003-01-01

    The neurofunctional system, which receives a photoperiod, is a photoperiodic brain system. As a part of chronoperiodic system of organism it is involved in perception and transfer of information about the main external Zeitgeber to the peripheral tissues. Such role of photoperiodic system allows it not only synchronize the chronorhythms of different somatic and visceral functions, but also realize the coordination and the modulation of adaptation mechanisms to the stressors influence. The present review is focused on the ways of conduction of photoperiodic information, role of suprachiasmatic nuclei of hypothalamus in endogenous oscillation of chronorhythms and pineal gland as a neuroendocrinal transducer; and also on characteristics of circadian and circannual parts of photoperiodic system. Special attention is given to vegetative part of photoperiodic system and melatonin--"the hormone of dark". It is supposed that adenosine, one of the humoral elements of photoperiodic system, is involved in transfer of duration of the light part of photoperiod. Due to presented data we have come to the conclusion that septohippocampal system is one of the center for saving photoperiodic information. PMID:14658302

  12. Basic, specific, mechanistic? Conceptualizing musical emotions in the brain.

    PubMed

    Omigie, Diana

    2016-06-01

    The number of studies investigating music processing in the human brain continues to increase, with a large proportion of them focussing on the correlates of so-called musical emotions. The current Review highlights the recent development whereby such studies are no longer concerned only with basic emotions such as happiness and sadness but also with so-called music-specific or "aesthetic" ones such as nostalgia and wonder. It also highlights how mechanisms such as expectancy and empathy, which are seen as inducing musical emotions, are enjoying ever-increasing investigation and substantiation with physiological and neuroimaging methods. It is proposed that a combination of these approaches, namely, investigation of the precise mechanisms through which so-called music-specific or aesthetic emotions may arise, will provide the most important advances for our understanding of the unique nature of musical experience. J. Comp. Neurol. 524:1676-1686, 2016. © 2015 Wiley Periodicals, Inc. PMID:26172307

  13. Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression

    PubMed Central

    Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Dombrowski, Stephen M.; Miller, Tyler E.; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; von Elverfeldt, Dominik; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.; Bredel, Markus

    2014-01-01

    Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones. PMID:24865424

  14. Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression.

    PubMed

    Ferrarese, Roberto; Harsh, Griffith R; Yadav, Ajay K; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Dombrowski, Stephen M; Miller, Tyler E; Masilamani, Anie P; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M; Yu, Irene L Y; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; von Elverfeldt, Dominik; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W; He, Xiaolin; Prinz, Marco; Chandler, James P; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N; Carro, Maria S; Bredel, Markus

    2014-07-01

    Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones. PMID:24865424

  15. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

    ... and Updates News from the RSNA Annual Meeting Violent Video Games Alter Brain Function in Young Men ... Using functional MRI, researchers have found that playing violent video games for one week causes changes in ...

  16. Persistent Postconcussive Symptoms Are Accompanied by Decreased Functional Brain Oxygenation.

    PubMed

    Helmich, Ingo; Saluja, Rajeet S; Lausberg, Hedda; Kempe, Mathias; Furley, Philip; Berger, Alisa; Chen, Jen-Kai; Ptito, Alain

    2015-01-01

    Diagnostic methods are considered a major concern in the determination of mild traumatic brain injury. The authors examined brain oxygenation patterns in subjects with severe and minor persistent postconcussive difficulties and a healthy control group during working memory tasks in prefrontal brain regions using functional near-infrared spectroscopy. The results demonstrated decreased working memory performances among concussed subjects with severe postconcussive symptoms that were accompanied by decreased brain oxygenation patterns. An association appears to exist between decreased brain oxygenation, poor performance of working memory tasks, and increased symptom severity scores in subjects suffering from persistent postconcussive symptoms. PMID:25803447

  17. Graph Analysis of Functional Brain Networks for Cognitive Control of Action in Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H.; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P.

    2012-01-01

    Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly…

  18. Graph Analysis of Functional Brain Networks for Cognitive Control of Action in Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Caeyenberghs, Karen; Leemans, Alexander; Heitger, Marcus H.; Leunissen, Inge; Dhollander, Thijs; Sunaert, Stefan; Dupont, Patrick; Swinnen, Stephan P.

    2012-01-01

    Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly

  19. Functional Neuroanatomy of Executive Function after Neonatal Brain Injury in Adults Who Were Born Very Preterm

    PubMed Central

    Kalpakidou, Anastasia K.; Allin, Matthew P. G.; Walshe, Muriel; Giampietro, Vincent; McGuire, Philip K.; Rifkin, Larry; Murray, Robin M.; Nosarti, Chiara

    2014-01-01

    Individuals who were born very preterm (VPT; <33 gestational weeks) are at risk of experiencing deficits in tasks involving executive function in childhood and beyond. In addition, the type and severity of neonatal brain injury associated with very preterm birth may exert differential effects on executive functioning by altering its neuroanatomical substrates. Here we addressed this question by investigating with functional magnetic resonance imaging (fMRI) the haemodynamic response during executive-type processing using a phonological verbal fluency and a working memory task in VPT-born young adults who had experienced differing degrees of neonatal brain injury. 12 VPT individuals with a history of periventricular haemorrhage and ventricular dilatation (PVH+VD), 17 VPT individuals with a history of uncomplicated periventricular haemorrhage (UPVH), 13 VPT individuals with no history of neonatal brain injury and 17 controls received an MRI scan whilst completing a verbal fluency task with two cognitive loads (‘easy’ and ‘hard’ letters). Two groups of VPT individuals (PVH+VD; n = 10, UPVH; n = 8) performed an n-back task with three cognitive loads (1-, 2-, 3-back). Results demonstrated that VPT individuals displayed hyperactivation in frontal, temporal, and parietal cortices and in caudate nucleus, insula and thalamus compared to controls, as demands of the verbal fluency task increased, regardless of type of neonatal brain injury. On the other hand, during the n-back task and as working memory load increased, the PVH+VD group showed less engagement of the frontal cortex than the UPVH group. In conclusion, this study suggests that the functional neuroanatomy of different executive-type processes is altered following VPT birth and that neural activation associated with specific aspects of executive function (i.e., working memory) may be particularly sensitive to the extent of neonatal brain injury. PMID:25438043

  20. Bisphenol A Interaction With Brain Development and Functions

    PubMed Central

    2015-01-01

    Brain development is an organized, but constantly adaptive, process in which genetic and epigenetic signals allow neurons to differentiate, to migrate, and to develop correct connections. Gender specific prenatal sex hormone milieu participates in the dimorphic development of many neuronal networks. Environmental cues may interfere with these developmental programs, producing adverse outcomes. Bisphenol A (BPA), an estrogenic/antiandrogenic endocrine disruptor widely diffused in the environment, produces adverse effects at levels below the acceptable daily intake. This review analyzes the recent literature on the consequences of perinatal exposure to BPA environmental doses on the development of a dimorphic brain. The BPA interference with the development and function of the neuroendocrine hypothalamus and of the nuclei controlling energy balance, and with the hippocampal memory processing is also discussed. The detrimental action of BPA appears complex, involving different hormonal and epigenetic pathways activated, often in a dimorphic way, within clearcut susceptibility windows. To date, discrepancies in experimental approaches and in related outcomes make unfeasible to translate the available information into clear dose–response models for human risk assessment. Evaluation of BPA brain levels in relation to the appearance of adverse effects in future basic studies will certainly give better definition of the warning threshold for human health. PMID:26672480

  1. Functionally driven brain networks using multi-layer graph clustering.

    PubMed

    Ghanbari, Yasser; Bloy, Luke; Shankar, Varsha; Edgar, J Christopher; Roberts, Timothy P L; Schultz, Robert T; Verma, Ragini

    2014-01-01

    Connectivity analysis of resting state brain has provided a novel means of investigating brain networks in the study of neurodevelpmental disorders. The study of functional networks, often represented by high dimensional graphs, predicates on the ability of methods in succinctly extracting meaningful representative connectivity information at the subject and population level. This need motivates the development of techniques that can extract underlying network modules that characterize the connectivity in a population, while capturing variations of these modules at the individual level. In this paper, we propose a multi-layer raph clustering technique that fuses the information from a collection of connectivity networks of a population to extract the underlying common network modules that serve as network hubs for the population. These hubs form a functional network atlas. In addition, our technique provides subject-specific factors designed to characterize and quantify the degree of intra- and inter- connectivity between hubs, thereby providing a representation that is amenable to group level statistical analyses. We demonstrate the utility of the technique by creating a population network atlas of connectivity by examining MEG based functional connectivity in typically developing children, and using this to describe the individualized variation in those diagnosed with autism spectrum disorder. PMID:25320789

  2. Mitochondrial function in the brain links anxiety with social subordination.

    PubMed

    Hollis, Fiona; van der Kooij, Michael A; Zanoletti, Olivia; Lozano, Laura; Cantó, Carles; Sandi, Carmen

    2015-12-15

    Dominance hierarchies are integral aspects of social groups, yet whether personality traits may predispose individuals to a particular rank remains unclear. Here we show that trait anxiety directly influences social dominance in male outbred rats and identify an important mediating role for mitochondrial function in the nucleus accumbens. High-anxious animals that are prone to become subordinate during a social encounter with a low-anxious rat exhibit reduced mitochondrial complex I and II proteins and respiratory capacity as well as decreased ATP and increased ROS production in the nucleus accumbens. A causal link for these findings is indicated by pharmacological approaches. In a dyadic contest between anxiety-matched animals, microinfusion of specific mitochondrial complex I or II inhibitors into the nucleus accumbens reduced social rank, mimicking the low probability to become dominant observed in high-anxious animals. Conversely, intraaccumbal infusion of nicotinamide, an amide form of vitamin B3 known to enhance brain energy metabolism, prevented the development of a subordinate status in high-anxious individuals. We conclude that mitochondrial function in the nucleus accumbens is crucial for social hierarchy establishment and is critically involved in the low social competitiveness associated with high anxiety. Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders. PMID:26621716

  3. Mitochondrial function in the brain links anxiety with social subordination

    PubMed Central

    Hollis, Fiona; van der Kooij, Michael A.; Zanoletti, Olivia; Lozano, Laura; Cantó, Carles; Sandi, Carmen

    2015-01-01

    Dominance hierarchies are integral aspects of social groups, yet whether personality traits may predispose individuals to a particular rank remains unclear. Here we show that trait anxiety directly influences social dominance in male outbred rats and identify an important mediating role for mitochondrial function in the nucleus accumbens. High-anxious animals that are prone to become subordinate during a social encounter with a low-anxious rat exhibit reduced mitochondrial complex I and II proteins and respiratory capacity as well as decreased ATP and increased ROS production in the nucleus accumbens. A causal link for these findings is indicated by pharmacological approaches. In a dyadic contest between anxiety-matched animals, microinfusion of specific mitochondrial complex I or II inhibitors into the nucleus accumbens reduced social rank, mimicking the low probability to become dominant observed in high-anxious animals. Conversely, intraaccumbal infusion of nicotinamide, an amide form of vitamin B3 known to enhance brain energy metabolism, prevented the development of a subordinate status in high-anxious individuals. We conclude that mitochondrial function in the nucleus accumbens is crucial for social hierarchy establishment and is critically involved in the low social competitiveness associated with high anxiety. Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders. PMID:26621716

  4. Enzyme Specific Activity in Functionalized Nanoporous Supports

    SciTech Connect

    Lei, Chenghong; Soares, Thereza A.; Shin, Yongsoon; Liu, Jun; Ackerman, Eric J.

    2008-03-26

    Enzyme specific activity can be increased or decreased to a large extent by changing protein loading density in functionalized nanoporous support, where organophosphorus hydrolase can display a constructive orientation and thus leave a completely open entrance for substrate even at higher protein loading density, but glucose oxidase can not.

  5. What drives the organization of object knowledge in the brain? The distributed domain-specific hypothesis

    PubMed Central

    Mahon, Bradford Z.; Caramazza, Alfonso

    2011-01-01

    Various forms of category-specificity have been described at both the cognitive and neural levels, inviting the inference that different semantic domains are processed by distinct, dedicated mechanisms. Here we argue for an extension of a Domain-Specific interpretation to these phenomena that is based on network-level analyses of functional coupling among brain regions. On this view, domain-specificity in one region of the brain emerges because of innate connectivity with a network of regions that also process information about that domain. Recent findings are reviewed that converge with this framework, and a new direction is outlined for understanding the neural principles that shape the organization of conceptual knowledge. PMID:21317022

  6. [Acceptor of action results as a structural functional basis of dynamic stereotype activities of the brain].

    PubMed

    Sudakov, K V

    2005-01-01

    The system mechanisms of brain dynamic stereotypes formation are considered. The brain dynamic stereotypes are shown to be formed on the structures of acceptor of action results by dominating motivations and reinforcements. Acceptors of action results are widely spread in brain structures. They are presented in functional systems which form behavioral acts of animals with spreading neural excitations in collaterals of axons of pyramidal tract. Reinforcing excitations form specific architectonic of acceptors of action results, which include brain structures corresponding to modalities of parameters of reinforcements. Dominating motivations, which predict future events, excite molecular engrams of action results which were formed by previous reinforcements. PMID:15895870

  7. Localization of specific erythropoietin binding sites in defined areas of the mouse brain.

    PubMed Central

    Digicaylioglu, M; Bichet, S; Marti, H H; Wenger, R H; Rivas, L A; Bauer, C; Gassmann, M

    1995-01-01

    The main physiological regulator of erythropoiesis is the hematopoietic growth factor erythropoietin (EPO), which is induced in response to hypoxia. Binding of EPO to the EPO receptor (EPO-R), a member of the cytokine receptor superfamily, controls the terminal maturation of red blood cells. So far, EPO has been reported to act mainly on erythroid precursor cells. However, we have detected mRNA encoding both EPO and EPO-R in mouse brain by reverse transcription-PCR. Exposure to 0.1% carbon monoxide, a procedure that causes functional anemia, resulted in a 20-fold increase of EPO mRNA in mouse brain as quantified by competitive reverse transcription-PCR, whereas the EPO-R mRNA level was not influenced by hypoxia. Binding studies on mouse brain sections revealed defined binding sites for radioiodinated EPO in distinct brain areas. The specificity of EPO binding was assessed by homologous competition with an excess of unlabeled EPO and by using two monoclonal antibodies against human EPO, one inhibitory and the other noninhibitory for binding of EPO to EPO-R. Major EPO binding sites were observed in the hippocampus, capsula interna, cortex, and midbrain areas. Functional expression of the EPO-R and hypoxic upregulation of EPO suggest a role of EPO in the brain. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7731971

  8. The Dynamic Dielectric at a Brain Functional Site and an EM Wave Approach to Functional Brain Imaging

    PubMed Central

    Li, X. P.; Xia, Q.; Qu, D.; Wu, T. C.; Yang, D. G.; Hao, W. D.; Jiang, X.; Li, X. M.

    2014-01-01

    Functional brain imaging has tremendous applications. The existing methods for functional brain imaging include functional Magnetic Resonant Imaging (fMRI), scalp electroencephalography (EEG), implanted EEG, magnetoencephalography (MEG) and Positron Emission Tomography (PET), which have been widely and successfully applied to various brain imaging studies. To develop a new method for functional brain imaging, here we show that the dielectric at a brain functional site has a dynamic nature, varying with local neuronal activation as the permittivity of the dielectric varies with the ion concentration of the extracellular fluid surrounding neurons in activation. Therefore, the neuronal activation can be sensed by a radiofrequency (RF) electromagnetic (EM) wave propagating through the site as the phase change of the EM wave varies with the permittivity. Such a dynamic nature of the dielectric at a brain functional site provides the basis for an RF EM wave approach to detecting and imaging neuronal activation at brain functional sites, leading to an RF EM wave approach to functional brain imaging. PMID:25367217

  9. Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus

    PubMed Central

    Zhang, Jiyong; Sadowska, Grazyna B.; Chen, Xiaodi; Park, Seon Yeong; Kim, Jeong-Eun; Bodge, Courtney A.; Cummings, Erin; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Stonestreet, Barbara S.

    2015-01-01

    Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti–IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti–IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti–IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia.—Zhang, J., Sadowska, G. B., Chen, X., Park, S. Y., Kim, J.-E., Bodge, C. A., Cummings, E., Lim, Y.-P., Makeyev, O., Besio, W. G., Gaitanis, J., Banks, W. A., Stonestreet, B. S. Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus. PMID:25609424

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

    PubMed

    Supekar, Kaustubh; Musen, Mark; Menon, Vinod

    2009-07-01

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

  11. Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling

    PubMed Central

    Brankatschk, Marko; Dunst, Sebastian; Nemetschke, Linda; Eaton, Suzanne

    2014-01-01

    The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content. DOI: http://dx.doi.org/10.7554/eLife.02862.001 PMID:25275323

  12. Gut Microbiota and Brain Function: An Evolving Field in Neuroscience.

    PubMed

    Foster, Jane A; Lyte, Mark; Meyer, Emeran; Cryan, John F

    2016-05-01

    There is a growing appreciation of the importance of gut microbiota to health and disease. This has been driven by advances in sequencing technology and recent findings demonstrating the important role of microbiota in common health disorders such as obesity. Moreover, the potential role of gut microbiota in influencing brain function, behavior, and mental health has attracted the attention of neuroscientists and psychiatrists. At the 29(th) International College of Neuropsychopharmacology (CINP) World Congress held in Vancouver, Canada, in June 2014, a group of experts presented the symposium, "Gut microbiota and brain function: Relevance to psychiatric disorders" to review the latest findings in how gut microbiota may play a role in brain function, behavior, and disease. The symposium covered a broad range of topics, including gut microbiota and neuroendocrine function, the influence of gut microbiota on behavior, probiotics as regulators of brain and behavior, and imaging the gut-brain axis in humans. This report provides an overview of these presentations. PMID:26438800

  13. Proteomics Identification of Specifically Carbonylated Brain Proteins in APPNLh/APPNLh x PS-1P264L/PS-1P264L Human Double Mutant Knock-in Mice Model of Alzheimer Disease as a Function of Age

    PubMed Central

    Sultana, Rukhsana; Robinson, Renã A. S.; Di Domenico, Fabio; Mohmmad Abdul, Hafiz; St. Clair, Daret K.; Markesbery, William R.; Cai, Jian; Pierce, William M.; Butterfield, D. Allan

    2011-01-01

    Alzheimer disease (AD) is the most common type of dementia and is characterized pathologically by the presence of neurofibrillary tangles (NFTs), senile plaques (SPs), and loss of synapses. The main component of SP is amyloid-beta peptide (Aβ), a 39 to 43 amino acid peptide, generated by the proteolytic cleavage of amyloid precursor protein (APP) by the action of beta- and gamma-secretases. The presenilins (PS) are components of the γ-secretase, which contains the protease active center. Mutations in PS enhance the production of the Aβ42 peptide. To date, more than 160 mutations in PS1 have been identified. Many PS mutations increase the production of the β-secretase-mediated C-terminal (CT) 99 amino acid-long fragment (CT99), which is subsequently cleaved by γ-secretase to yield Aβ peptides. Aβ has been proposed to induce oxidative stress and neurotoxicity. Previous studies from our laboratory and others showed an age-dependent increase in oxidative stress markers, loss of lipid asymmetry, and Aβ production and amyloid deposition in the brain of APP/PS1 mice. In the present study, we used APPNLh/APPNLh x PS-1P246L/PS-1P246L human double mutant knock-in APP/PS-1 mice to identify specific targets of brain protein carbonylation in an age-dependent manner. We found a number of proteins that are oxidatively modified in APP/PS1 mice compared to age-matched controls. The relevance of the identified proteins to the progression and pathogenesis of AD is discussed. PMID:21726674

  14. Segment-specific requirements for dorsoventral patterning genes during early brain development in Drosophila.

    PubMed

    Urbach, Rolf; Volland, Dagmar; Seibert, Janina; Technau, Gerhard M

    2006-11-01

    An initial step in the development of the Drosophila central nervous system is the delamination of a stereotype population of neural stem cells (neuroblasts, NBs) from the neuroectoderm. Expression of the columnar genes ventral nervous system defective (vnd), intermediate neuroblasts defective (ind) and muscle segment homeobox (msh) subdivides the truncal neuroectoderm (primordium of the ventral nerve cord) into a ventral, intermediate and dorsal longitudinal domain, and has been shown to play a key role in the formation and/or specification of corresponding NBs. In the procephalic neuroectoderm (pNE, primordium of the brain), expression of columnar genes is highly complex and dynamic, and their functions during brain development are still unknown. We have investigated the role of these genes (with special emphasis on the Nkx2-type homeobox gene vnd) in early embryonic development of the brain. We show at the level of individually identified cells that vnd controls the formation of ventral brain NBs and is required, and to some extent sufficient, for the specification of ventral and intermediate pNE and deriving NBs. However, we uncovered significant differences in the expression of and regulatory interactions between vnd, ind and msh among brain segments, and in comparison to the ventral nerve cord. Whereas in the trunk Vnd negatively regulates ind, Vnd does not repress ind (but does repress msh) in the ventral pNE and NBs. Instead, in the deutocerebral region, Vnd is required for the expression of ind. We also show that, in the anterior brain (protocerebrum), normal production of early glial cells is independent from msh and vnd, in contrast to the posterior brain (deuto- and tritocerebrum) and to the ventral nerve cord. PMID:17038517

  15. Evidence for hubs in human functional brain networks

    PubMed Central

    Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E

    2013-01-01

    Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601

  16. Beyond localized and distributed accounts of brain functions. Comment on Understanding brain networks and brain organization by Pessoa

    NASA Astrophysics Data System (ADS)

    Cauda, Franco; Costa, Tommaso; Tamietto, Marco

    2014-09-01

    Recent evidence in cognitive neuroscience lends support to the idea that network models of brain architecture provide a privileged access to the understanding of the relation between brain organization and cognitive processes [1]. The core perspective holds that cognitive processes depend on the interactions among distributed neuronal populations and brain structures, and that the impact of a given region on behavior largely depends on its pattern of anatomical and functional connectivity [2,3].

  17. Ribosome Profiling Reveals a Cell-Type-Specific Translational Landscape in Brain Tumors

    PubMed Central

    Gonzalez, Christian; Sims, Jennifer S.; Hornstein, Nicholas; Mela, Angeliki; Garcia, Franklin; Lei, Liang; Gass, David A.; Amendolara, Benjamin; Bruce, Jeffrey N.

    2014-01-01

    Glioma growth is driven by signaling that ultimately regulates protein synthesis. Gliomas are also complex at the cellular level and involve multiple cell types, including transformed and reactive cells in the brain tumor microenvironment. The distinct functions of the various cell types likely lead to different requirements and regulatory paradigms for protein synthesis. Proneural gliomas can arise from transformation of glial progenitors that are driven to proliferate via mitogenic signaling that affects translation. To investigate translational regulation in this system, we developed a RiboTag glioma mouse model that enables cell-type-specific, genome-wide ribosome profiling of tumor tissue. Infecting glial progenitors with Cre-recombinant retrovirus simultaneously activates expression of tagged ribosomes and delivers a tumor-initiating mutation. Remarkably, we find that although genes specific to transformed cells are highly translated, their translation efficiencies are low compared with normal brain. Ribosome positioning reveals sequence-dependent regulation of ribosomal activity in 5′-leaders upstream of annotated start codons, leading to differential translation in glioma compared with normal brain. Additionally, although transformed cells express a proneural signature, untransformed tumor-associated cells, including reactive astrocytes and microglia, express a mesenchymal signature. Finally, we observe the same phenomena in human disease by combining ribosome profiling of human proneural tumor and non-neoplastic brain tissue with computational deconvolution to assess cell-type-specific translational regulation. PMID:25122893

  18. 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

  19. Functional specializations for music processing in the human newborn brain.

    PubMed

    Perani, Daniela; Saccuman, Maria Cristina; Scifo, Paola; Spada, Danilo; Andreolli, Guido; Rovelli, Rosanna; Baldoli, Cristina; Koelsch, Stefan

    2010-03-01

    In adults, specific neural systems with right-hemispheric weighting are necessary to process pitch, melody, and harmony as well as structure and meaning emerging from musical sequences. It is not known to what extent the specialization of these systems results from long-term exposure to music or from neurobiological constraints. One way to address this question is to examine how these systems function at birth, when auditory experience is minimal. We used functional MRI to measure brain activity in 1- to 3-day-old newborns while they heard excerpts of Western tonal music and altered versions of the same excerpts. Altered versions either included changes of the tonal key or were permanently dissonant. Music evoked predominantly right-hemispheric activations in primary and higher order auditory cortex. During presentation of the altered excerpts, hemodynamic responses were significantly reduced in the right auditory cortex, and activations emerged in the left inferior frontal cortex and limbic structures. These results demonstrate that the infant brain shows a hemispheric specialization in processing music as early as the first postnatal hours. Results also indicate that the neural architecture underlying music processing in newborns is sensitive to changes in tonal key as well as to differences in consonance and dissonance. PMID:20176953

  20. Functional specializations for music processing in the human newborn brain

    PubMed Central

    Perani, Daniela; Saccuman, Maria Cristina; Scifo, Paola; Spada, Danilo; Andreolli, Guido; Rovelli, Rosanna; Baldoli, Cristina; Koelsch, Stefan

    2010-01-01

    In adults, specific neural systems with right-hemispheric weighting are necessary to process pitch, melody, and harmony as well as structure and meaning emerging from musical sequences. It is not known to what extent the specialization of these systems results from long-term exposure to music or from neurobiological constraints. One way to address this question is to examine how these systems function at birth, when auditory experience is minimal. We used functional MRI to measure brain activity in 1- to 3-day-old newborns while they heard excerpts of Western tonal music and altered versions of the same excerpts. Altered versions either included changes of the tonal key or were permanently dissonant. Music evoked predominantly right-hemispheric activations in primary and higher order auditory cortex. During presentation of the altered excerpts, hemodynamic responses were significantly reduced in the rig1ht auditory cortex, and activations emerged in the left inferior frontal cortex and limbic structures. These results demonstrate that the infant brain shows a hemispheric specialization in processing music as early as the first postnatal hours. Results also indicate that the neural architecture underlying music processing in newborns is sensitive to changes in tonal key as well as to differences in consonance and dissonance. PMID:20176953

  1. The Apolipoprotein E Gene, Attention, and Brain Function

    PubMed Central

    Parasuraman, Raja; Greenwood, Pamela M.; Sunderland, Trey

    2005-01-01

    The ɛ4 allele of the apolipoprotein E (ApoE) gene is associated with alterations in brain function and is a risk factor for Alzheimer’s disease (AD). Changes in components of visuospatial attention with ApoE-ɛ4, aging, and AD are described. Healthy middle-aged adults without dementia who have the ApoE-ɛ4 gene show deficits in spatial attention and working memory that are qualitatively similar to those seen in clinically diagnosed AD patients. The findings support an association between ApoE polymorphism and specific components of visuospatial attention. Molecular mechanisms that may mediate the ApoE–attention link by modulating cholinergic neurotransmission to the posterior parietal cortex are discussed. Studies of attention and brain function in ApoE-ɛ4 carriers without dementia can advance knowledge of the genetics of visual attention, may enhance understanding of the preclinical phase of AD, and may lead to better methods for early AD detection. PMID:11949718

  2. Regional specificity in deltamethrin induced cytochrome P450 expression in rat brain

    SciTech Connect

    Yadav, Sanjay; Johri, Ashu; Dhawan, Alok; Seth, Prahlad K.; Parmar, Devendra . E-mail: parmar_devendra@hotmail.com

    2006-11-15

    Oral administration of deltamethrin (5 mg/kg x 7 or 15 or 21 days) was found to produce a time-dependent increase in the mRNA expression of xenobiotic metabolizing cytochrome P450 1A1 (CYP1A1), 1A2 and CYP2B1, 2B2 isoenzymes in rat brain. RT-PCR studies further showed that increase in the mRNA expression of these CYP isoenzymes observed after 21 days of exposure was region specific. Hippocampus exhibited maximum increase in the mRNA expression of CYP1A1, which was followed by pons-medulla, cerebellum and hypothalamus. The mRNA expression of CYP2B1 also exhibited maximum increase in the hypothalamus and hippocampus followed by almost similar increase in midbrain and cerebellum. In contrast, mRNA expression of CYP1A2 and CYP2B2, the constitutive isoenzymes exhibited relatively higher increase in pons-medulla, cerebellum and frontal cortex. Immunoblotting studies carried out with polyclonal antibody raised against rat liver CYP1A1/1A2 or CYP2B1/2B2 isoenzymes also showed increase in immunoreactivity comigrating with CYP1A1/1A2 or 2B1/2B2 in the microsomal fractions isolated from hippocampus, hypothalamus and cerebellum of rat treated with deltamethrin. Though the exact relationship of the xenobiotic metabolizing CYPs with the physiological function of the brain is yet to be clearly understood, the increase in the mRNA expression of the CYPs in the brain regions that regulate specific brain functions affected by deltamethrin have further indicated that modulation of these CYPs could be associated with the various endogenous functions of the brain.

  3. An Evolutionary Computation Approach to Examine Functional Brain Plasticity

    PubMed Central

    Roy, Arnab; Campbell, Colin; Bernier, Rachel A.; Hillary, Frank G.

    2016-01-01

    One common research goal in systems neurosciences is to understand how the functional relationship between a pair of regions of interest (ROIs) evolves over time. Examining neural connectivity in this way is well-suited for the study of developmental processes, learning, and even in recovery or treatment designs in response to injury. For most fMRI based studies, the strength of the functional relationship between two ROIs is defined as the correlation between the average signal representing each region. The drawback to this approach is that much information is lost due to averaging heterogeneous voxels, and therefore, the functional relationship between a ROI-pair that evolve at a spatial scale much finer than the ROIs remain undetected. To address this shortcoming, we introduce a novel evolutionary computation (EC) based voxel-level procedure to examine functional plasticity between an investigator defined ROI-pair by simultaneously using subject-specific BOLD-fMRI data collected from two sessions seperated by finite duration of time. This data-driven procedure detects a sub-region composed of spatially connected voxels from each ROI (a so-called sub-regional-pair) such that the pair shows a significant gain/loss of functional relationship strength across the two time points. The procedure is recursive and iteratively finds all statistically significant sub-regional-pairs within the ROIs. Using this approach, we examine functional plasticity between the default mode network (DMN) and the executive control network (ECN) during recovery from traumatic brain injury (TBI); the study includes 14 TBI and 12 healthy control subjects. We demonstrate that the EC based procedure is able to detect functional plasticity where a traditional averaging based approach fails. The subject-specific plasticity estimates obtained using the EC-procedure are highly consistent across multiple runs. Group-level analyses using these plasticity estimates showed an increase in the strength of functional relationship between DMN and ECN for TBI subjects, which is consistent with prior findings in the TBI-literature. The EC-approach also allowed us to separate sub-regional-pairs contributing to positive and negative plasticity; the detected sub-regional-pairs significantly overlap across runs thus highlighting the reliability of the EC-approach. These sub-regional-pairs may be useful in performing nuanced analyses of brain-behavior relationships during recovery from TBI. PMID:27092047

  4. Functional connectivity of the rodent brain using optical imaging

    NASA Astrophysics Data System (ADS)

    Guevara Codina, Edgar

    The aim of this thesis is to apply functional connectivity in a variety of animal models, using several optical imaging modalities. Even at rest, the brain shows high metabolic activity: the correlation in slow spontaneous fluctuations identifies remotely connected areas of the brain; hence the term "functional connectivity". Ongoing changes in spontaneous activity may provide insight into the neural processing that takes most of the brain metabolic activity, and so may provide a vast source of disease related changes. Brain hemodynamics may be modified during disease and affect resting-state activity. The thesis aims to better understand these changes in functional connectivity due to disease, using functional optical imaging. The optical imaging techniques explored in the first two contributions of this thesis are Optical Imaging of Intrinsic Signals and Laser Speckle Contrast Imaging, together they can estimate the metabolic rate of oxygen consumption, that closely parallels neural activity. They both have adequate spatial and temporal resolution and are well adapted to image the convexity of the mouse cortex. In the last article, a depth-sensitive modality called photoacoustic tomography was used in the newborn rat. Optical coherence tomography and laminar optical tomography were also part of the array of imaging techniques developed and applied in other collaborations. The first article of this work shows the changes in functional connectivity in an acute murine model of epileptiform activity. Homologous correlations are both increased and decreased with a small dependence on seizure duration. These changes suggest a potential decoupling between the hemodynamic parameters in resting-state networks, underlining the importance to investigate epileptic networks with several independent hemodynamic measures. The second study examines a novel murine model of arterial stiffness: the unilateral calcification of the right carotid. Seed-based connectivity analysis showed a decreasing trend of homologous correlation in the motor and cingulate cortices. Graph analyses showed a randomization of the cortex functional networks, suggesting a loss of connectivity, more specifically in the motor cortex ipsilateral to the treated carotid; however these changes are not reflected in differentiated metabolic estimates. Confounds remain due to the fact that carotid rigidification gives rise to neural decline in the hippocampus as well as unilateral alteration of vascular pulsatility; however the results support the need to look at several hemodynamic parameters when imaging the brain after arterial remodeling. The third article of this thesis studies a model of inflammatory injury on the newborn rat. Oxygen saturation and functional connectivity were assessed with photoacoustic tomography. Oxygen saturation was decreased in the site of the lesion and on the cortex ipsilateral to the injury; however this decrease is not fully explained by hypovascularization revealed by histology. Seed-based functional connectivity analysis showed that inter-hemispheric connectivity is not affected by inflammatory injury.

  5. The blind brain: how (lack of) vision shapes the morphological and functional architecture of the human brain.

    PubMed

    Ricciardi, Emiliano; Handjaras, Giacomo; Pietrini, Pietro

    2014-11-01

    Since the early days, how we represent the world around us has been a matter of philosophical speculation. Over the last few decades, modern neuroscience, and specifically the development of methodologies for the structural and the functional exploration of the brain have made it possible to investigate old questions with an innovative approach. In this brief review, we discuss the main findings from a series of brain anatomical and functional studies conducted in sighted and congenitally blind individuals by our's and others' laboratories. Historically, research on the 'blind brain' has focused mainly on the cross-modal plastic changes that follow sensory deprivation. More recently, a novel line of research has been developed to determine to what extent visual experience is truly required to achieve a representation of the surrounding environment. Overall, the results of these studies indicate that most of the brain fine morphological and functional architecture is programmed to develop and function independently from any visual experience. Distinct cortical areas are able to process information in a supramodal fashion, that is, independently from the sensory modality that carries that information to the brain. These observations strongly support the hypothesis of a modality-independent, i.e. more abstract, cortical organization, and may contribute to explain how congenitally blind individuals may interact efficiently with an external world that they have never seen. PMID:24962172

  6. Complex Networks - A Key to Understanding Brain Function

    ScienceCinema

    Olaf Sporns

    2010-01-08

    The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

  7. Complex Networks - A Key to Understanding Brain Function

    SciTech Connect

    Olaf Sporns

    2008-01-23

    The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

  8. Complex Networks - A Key to Understanding Brain Function

    SciTech Connect

    Sporns, Olaf

    2008-01-23

    The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life. How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood. In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

  9. Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128

    PubMed Central

    2014-01-01

    MicroRNAs, the non-coding single-stranded RNA of 19–25 nucleotides are emerging as robust players of gene regulation. Plethora of evidences support that the ability of microRNAs to regulate several genes of a pathway or even multiple cross talking pathways have significant impact on a complex regulatory network and ultimately the physiological processes and diseases. Brain being a complex organ with several cell types, expresses more distinct miRNAs than any other tissues. This review aims to discuss about the microRNAs in brain development, function and their dysfunction in brain tumors. We also provide a comprehensive summary of targets of brain specific and brain enriched miRNAs that contribute to the diversity and plasticity of the brain. In particular, we uncover recent findings on miRNA-128, a brain-enriched microRNA that is induced during neuronal differentiation and whose aberrant expression has been reported in several cancers. This review describes the wide spectrum of targets of miRNA-128 that have been identified till date with potential roles in apoptosis, angiogenesis, proliferation, cholesterol metabolism, self renewal, invasion and cancer progression and how this knowledge might be exploited for the development of future miRNA-128 based therapies for the treatment of cancer as well as metabolic diseases. PMID:24555688

  10. Mapping Functional Brain Development: Building a Social Brain through Interactive Specialization

    ERIC Educational Resources Information Center

    Johnson, Mark H.; Grossmann, Tobias; Kadosh, Kathrin Cohen

    2009-01-01

    The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the "social brain." They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied--the emergence of social

  11. Mapping Functional Brain Development: Building a Social Brain through Interactive Specialization

    ERIC Educational Resources Information Center

    Johnson, Mark H.; Grossmann, Tobias; Kadosh, Kathrin Cohen

    2009-01-01

    The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the "social brain." They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied--the emergence of social…

  12. Brain Hemispheric Functions and the Native American.

    ERIC Educational Resources Information Center

    Ross, Allen Chuck

    1982-01-01

    Uses brain research conducted by Dr. Roger Sperry to show that traditional Native Americans are more dominant in right hemisphere thinking, setting them apart from a modern left hemisphere-oriented society (especially emphasized in schools). Describes some characteristics of Native American thinking that illustrate a right hemisphere orientation

  13. Generating Text from Functional Brain Images

    PubMed Central

    Pereira, Francisco; Detre, Greg; Botvinick, Matthew

    2011-01-01

    Recent work has shown that it is possible to take brain images acquired during viewing of a scene and reconstruct an approximation of the scene from those images. Here we show that it is also possible to generate text about the mental content reflected in brain images. We began with images collected as participants read names of concrete items (e.g., “Apartment’’) while also seeing line drawings of the item named. We built a model of the mental semantic representation of concrete concepts from text data and learned to map aspects of such representation to patterns of activation in the corresponding brain image. In order to validate this mapping, without accessing information about the items viewed for left-out individual brain images, we were able to generate from each one a collection of semantically pertinent words (e.g., “door,” “window” for “Apartment’’). Furthermore, we show that the ability to generate such words allows us to perform a classification task and thus validate our method quantitatively. PMID:21927602

  14. Brain Hemispheric Functions and the Native American.

    ERIC Educational Resources Information Center

    Ross, Allen Chuck

    1982-01-01

    Uses brain research conducted by Dr. Roger Sperry to show that traditional Native Americans are more dominant in right hemisphere thinking, setting them apart from a modern left hemisphere-oriented society (especially emphasized in schools). Describes some characteristics of Native American thinking that illustrate a right hemisphere orientation…

  15. Neural Substrate Expansion for the Restoration of Brain Function

    PubMed Central

    Chen, H. Isaac; Jgamadze, Dennis; Serruya, Mijail D.; Cullen, D. Kacy; Wolf, John A.; Smith, Douglas H.

    2016-01-01

    Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not demonstrated the ability to reestablish the function of large-scale neuronal networks. In this review, we contend that fulfilling the potential of brain substrate expansion will require a significant shift from current methods that emphasize direct manipulations of the brain (e.g., injections of cellular suspensions and the implantation of multi-electrode arrays) to the generation of more sophisticated neural tissues and neural-electric hybrids in vitro that are subsequently transplanted into the brain. Drawing from neural tissue engineering, stem cell biology, and neural interface technologies, this strategy makes greater use of the manifold techniques available in the laboratory to create biocompatible constructs that recapitulate brain architecture and thus are more easily recognized and utilized by brain networks. PMID:26834579

  16. Neural Substrate Expansion for the Restoration of Brain Function.

    PubMed

    Chen, H Isaac; Jgamadze, Dennis; Serruya, Mijail D; Cullen, D Kacy; Wolf, John A; Smith, Douglas H

    2016-01-01

    Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not demonstrated the ability to reestablish the function of large-scale neuronal networks. In this review, we contend that fulfilling the potential of brain substrate expansion will require a significant shift from current methods that emphasize direct manipulations of the brain (e.g., injections of cellular suspensions and the implantation of multi-electrode arrays) to the generation of more sophisticated neural tissues and neural-electric hybrids in vitro that are subsequently transplanted into the brain. Drawing from neural tissue engineering, stem cell biology, and neural interface technologies, this strategy makes greater use of the manifold techniques available in the laboratory to create biocompatible constructs that recapitulate brain architecture and thus are more easily recognized and utilized by brain networks. PMID:26834579

  17. Cell-specific blood–brain barrier regulation in health and disease: a focus on hypoxia

    PubMed Central

    Engelhardt, S; Patkar, S; Ogunshola, O O

    2014-01-01

    The blood–brain barrier (BBB) is a complex vascular structure consisting of microvascular endothelial cells that line the vessel wall, astrocyte end-feet, pericytes, as well as the basal lamina. BBB cells act in concert to maintain the characteristic impermeable and low paracellular flux of the brain vascular network, thus ensuring a homeostatic neuronal environment. Alterations in BBB stability that occur during injury have dire consequences on disease progression and it is clear that BBB cell-specific responses, positive or negative, must make a significant contribution to injury outcome. Reduced oxygenation, or hypoxia, is a characteristic of many brain diseases that significantly increases barrier permeability. Recent data suggest that hypoxia-inducible factor (HIF-1), the master regulator of the hypoxic response, probably mediates many hypoxic effects either directly or indirectly via its target genes. This review discusses current knowledge of physiological cell-specific regulation of barrier function, their responses to hypoxia as well as consequences of hypoxic-and HIF-1-mediated mechanisms on barrier integrity during select brain diseases. In the final sections, the potential of current advances in targeting HIF-1 as a therapeutic strategy will be overviewed. PMID:24641185

  18. Functional principal component model for high-dimensional brain imaging.

    PubMed

    Zipunnikov, Vadim; Caffo, Brian; Yousem, David M; Davatzikos, Christos; Schwartz, Brian S; Crainiceanu, Ciprian

    2011-10-01

    We explore a connection between the singular value decomposition (SVD) and functional principal component analysis (FPCA) models in high-dimensional brain imaging applications. We formally link right singular vectors to principal scores of FPCA. This, combined with the fact that left singular vectors estimate principal components, allows us to deploy the numerical efficiency of SVD to fully estimate the components of FPCA, even for extremely high-dimensional functional objects, such as brain images. As an example, a FPCA model is fit to high-resolution morphometric (RAVENS) images. The main directions of morphometric variation in brain volumes are identified and discussed. PMID:21798354

  19. Videogame training strategy-induced change in brain function during a complex visuomotor task.

    PubMed

    Lee, Hyunkyu; Voss, Michelle W; Prakash, Ruchika Shaurya; Boot, Walter R; Vo, Loan T K; Basak, Chandramallika; Vanpatter, Matt; Gratton, Gabriele; Fabiani, Monica; Kramer, Arthur F

    2012-07-01

    Although changes in brain function induced by cognitive training have been examined, functional plasticity associated with specific training strategies is still relatively unexplored. In this study, we examined changes in brain function during a complex visuomotor task following training using the Space Fortress video game. To assess brain function, participants completed functional magnetic resonance imaging (fMRI) before and after 30 h of training with one of two training regimens: Hybrid Variable-Priority Training (HVT), with a focus on improving specific skills and managing task priority, or Full Emphasis Training (FET), in which participants simply practiced the game to obtain the highest overall score. Control participants received only 6 h of FET. Compared to FET, HVT learners reached higher performance on the game and showed less brain activation in areas related to visuo-spatial attention and goal-directed movement after training. Compared to the control group, HVT exhibited less brain activation in right dorsolateral prefrontal cortex (DLPFC), coupled with greater performance improvement. Region-of-interest analysis revealed that the reduction in brain activation was correlated with improved performance on the task. This study sheds light on the neurobiological mechanisms of improved learning from directed training (HVT) over non-directed training (FET), which is related to visuo-spatial attention and goal-directed motor planning, while separating the practice-based benefit, which is related to executive control and rule management. PMID:22504276

  20. A comprehensive study of whole-brain functional connectivity in children and young adults.

    PubMed

    Jolles, Dietsje D; van Buchem, Mark A; Crone, Eveline A; Rombouts, Serge A R B

    2011-02-01

    Over the past decade, examination of functional connectivity using functional magnetic resonance imaging has become an important tool to investigate functional changes in patient populations, healthy aging, and recently also child development. Most prior developmental studies focused on functional connectivity between brain regions important for cognitive or emotional control and the so-called "default-mode network." In the present study, we investigated whole-brain functional connectivity in children (11-13 years; N = 19) and young adults (19-25 years; N = 29), without a priori restrictions to specific regions. We found similar patterns of functionally connected regions in children and young adults, but there were differences in the size of functionally connected regions (i.e., the number of voxels), as well as in the strength of functional connectivity (i.e., the correlation value) between brain regions. This indicates that functional connectivity continues to change during adolescence. Developmental differences were found across the whole brain, but the effects differed for functional connectivity patterns associated with higher cognitive or emotional functions and functional connectivity patterns associated with basic visual and sensorimotor functions. Finally, we showed that the majority of functional connectivity differences could not be explained on the basis of gray matter density alone. PMID:20542991

  1. Maintaining older brain functionality: A targeted review.

    PubMed

    Ballesteros, Soledad; Kraft, Eduard; Santana, Silvina; Tziraki, Chariklia

    2015-08-01

    The unprecedented growth in the number of older adults in our society is accompanied by the exponential increase in the number of elderly people who will suffer cognitive decline and dementia in the next decades. This will create an enormous cost for governments, families and individuals. Brain plasticity and its role in brain adaptation to the process of aging is influenced by other changes as a result of co-morbidities, environmental factors, personality traits (psychosocial variables) and genetic and epigenetic factors. This review summarizes recent findings obtained mostly from interventional studies that aim to prevent and/or delay age-related cognitive decline in healthy adults. There are a multitude of such studies. In this paper, we focused our review on physical activity, computerized cognitive training and social enhancement interventions on improving cognition, physical health, independent living and wellbeing of older adults. The methodological limitations of some of these studies, and the need for new multi-domain synergistic interventions, based on current advances in neuroscience and social-brain theories, are discussed. PMID:26054789

  2. Exploring brain function from anatomical connectivity.

    PubMed

    Zamora-López, Gorka; Zhou, Changsong; Kurths, Jürgen

    2011-01-01

    The intrinsic relationship between the architecture of the brain and the range of sensory and behavioral phenomena it produces is a relevant question in neuroscience. Here, we review recent knowledge gained on the architecture of the anatomical connectivity by means of complex network analysis. It has been found that cortico-cortical networks display a few prominent characteristics: (i) modular organization, (ii) abundant alternative processing paths, and (iii) the presence of highly connected hubs. Additionally, we present a novel classification of cortical areas of the cat according to the role they play in multisensory connectivity. All these properties represent an ideal anatomical substrate supporting rich dynamical behaviors, facilitating the capacity of the brain to process sensory information of different modalities segregated and to integrate them toward a comprehensive perception of the real world. The results here exposed are mainly based on anatomical data of cats' brain, but further observations suggest that, from worms to humans, the nervous system of all animals might share these fundamental principles of organization. PMID:21734863

  3. Space shuttle configuration accounting functional design specification

    NASA Technical Reports Server (NTRS)

    1974-01-01

    An analysis is presented of the requirements for an on-line automated system which must be capable of tracking the status of requirements and engineering changes and of providing accurate and timely records. The functional design specification provides the definition, description, and character length of the required data elements and the interrelationship of data elements to adequately track, display, and report the status of active configuration changes. As changes to the space shuttle program levels II and III configuration are proposed, evaluated, and dispositioned, it is the function of the configuration management office to maintain records regarding changes to the baseline and to track and report the status of those changes. The configuration accounting system will consist of a combination of computers, computer terminals, software, and procedures, all of which are designed to store, retrieve, display, and process information required to track proposed and proved engineering changes to maintain baseline documentation of the space shuttle program levels II and III.

  4. Predicting regional neurodegeneration from the healthy brain functional connectome

    PubMed Central

    Zhou, Juan; Gennatas, Efstathios D.; Kramer, Joel H.; Miller, Bruce L.; Seeley, William W.

    2012-01-01

    Summary Neurodegenerative diseases target large-scale neural networks. Four competing mechanistic hypotheses have been proposed to explain network-based disease patterning: nodal stress, transneuronal spread, trophic failure, and shared vulnerability. Here, we used task-free fMRI to derive the healthy intrinsic connectivity patterns seeded by brain regions vulnerable to any of five distinct neurodegenerative diseases. These data enabled us to investigate how intrinsic connectivity in health predicts region-by-region vulnerability to disease. For each illness, specific regions emerged as critical network “epicenters” whose normal connectivity profiles most resembled the disease-associated atrophy pattern. Graph theoretical analyses in healthy subjects revealed that regions with higher total connectional flow and, more consistently, shorter functional paths to the epicenters, showed greater disease-related vulnerability. These findings best fit a transneuronal spread model of network-based vulnerability. Molecular pathological approaches may help clarify what makes each epicenter vulnerable to its targeting disease and how toxic protein species travel between networked brain structures. PMID:22445348

  5. Selectionist and Evolutionary Approaches to Brain Function: A Critical Appraisal

    PubMed Central

    Fernando, Chrisantha; Szathmáry, Eörs; Husbands, Phil

    2012-01-01

    We consider approaches to brain dynamics and function that have been claimed to be Darwinian. These include Edelman’s theory of neuronal group selection, Changeux’s theory of synaptic selection and selective stabilization of pre-representations, Seung’s Darwinian synapse, Loewenstein’s synaptic melioration, Adam’s selfish synapse, and Calvin’s replicating activity patterns. Except for the last two, the proposed mechanisms are selectionist but not truly Darwinian, because no replicators with information transfer to copies and hereditary variation can be identified in them. All of them fit, however, a generalized selectionist framework conforming to the picture of Price’s covariance formulation, which deliberately was not specific even to selection in biology, and therefore does not imply an algorithmic picture of biological evolution. Bayesian models and reinforcement learning are formally in agreement with selection dynamics. A classification of search algorithms is shown to include Darwinian replicators (evolutionary units with multiplication, heredity, and variability) as the most powerful mechanism for search in a sparsely occupied search space. Examples are given of cases where parallel competitive search with information transfer among the units is more efficient than search without information transfer between units. Finally, we review our recent attempts to construct and analyze simple models of true Darwinian evolutionary units in the brain in terms of connectivity and activity copying of neuronal groups. Although none of the proposed neuronal replicators include miraculous mechanisms, their identification remains a challenge but also a great promise. PMID:22557963

  6. Functional Brain Networks: Random, “Small World” or Deterministic?

    PubMed Central

    Blinowska, Katarzyna J.; Kaminski, Maciej

    2013-01-01

    Lately the problem of connectivity in brain networks is being approached frequently by graph theoretical analysis. In several publications based on bivariate estimators of relations between EEG channels authors reported random or “small world” structure of networks. The results of these works often have no relation to other evidence based on imaging, inverse solutions methods, physiological and anatomical data. Herein we try to find reasons for this discrepancy. We point out that EEG signals are very much interdependent, thus bivariate measures applied to them may produce many spurious connections. In fact, they may outnumber the true connections. Giving all connections equal weights, as it is usual in the framework of graph theoretical analysis, further enhances these spurious links. In effect, close to random and disorganized patterns of connections emerge. On the other hand, multivariate connectivity estimators, which are free of the artificial links, show specific, well determined patterns, which are in a very good agreement with other evidence. The modular structure of brain networks may be identified by multivariate estimators based on Granger causality and formalism of assortative mixing. In this way, the strength of coupling may be evaluated quantitatively. During working memory task, by means of multivariate Directed Transfer Function, it was demonstrated that the modules characterized by strong internal bonds exchange the information by weaker connections. PMID:24205313

  7. Recovery of function after brain injury in man.

    PubMed

    Teuber, H L

    1975-01-01

    Late after-effects of cerebral trauma are difficult to study because patients tend to be seen for persisting symptoms, and not simply for their lesions. We have tried to avoid this bias by recalling periodically, over the years, 520 men with known brain injuries incurred in World War II or in Korea or Vietnam. These men are seen irrespective of clinical need and all undergo intensive behavioural and neurological assessment, which still continues. For such groups, recovery is impressive, though one third shows persistent intellectual loss. In addition, some tasks reveal specific deficits enduring unchanged, after th first 2-3 yr, for the 20-30 yr of follow-up (e.g. visual field defects, certain auditory discrimination losses, trouble on various complex perceptual tasks). These lasting deficits are linked to the site and size of focal injury, often representing remnants of more severe initially-present disorders. The extent of recovery is correlated with age at the time of trauma, the youngest faring best. Extension of such studies to cases of early brain damage (birth to five years), as indicated by hemiparesis, shows the familiar 'escape' of language after early left-hemisphere lesions but this is achieved at a price, the price being borne by non-verbal functions that normally depend on the integrity of the right hemisphere. PMID:1045991

  8. Selectionist and evolutionary approaches to brain function: a critical appraisal.

    PubMed

    Fernando, Chrisantha; Szathmáry, Eörs; Husbands, Phil

    2012-01-01

    We consider approaches to brain dynamics and function that have been claimed to be Darwinian. These include Edelman's theory of neuronal group selection, Changeux's theory of synaptic selection and selective stabilization of pre-representations, Seung's Darwinian synapse, Loewenstein's synaptic melioration, Adam's selfish synapse, and Calvin's replicating activity patterns. Except for the last two, the proposed mechanisms are selectionist but not truly Darwinian, because no replicators with information transfer to copies and hereditary variation can be identified in them. All of them fit, however, a generalized selectionist framework conforming to the picture of Price's covariance formulation, which deliberately was not specific even to selection in biology, and therefore does not imply an algorithmic picture of biological evolution. Bayesian models and reinforcement learning are formally in agreement with selection dynamics. A classification of search algorithms is shown to include Darwinian replicators (evolutionary units with multiplication, heredity, and variability) as the most powerful mechanism for search in a sparsely occupied search space. Examples are given of cases where parallel competitive search with information transfer among the units is more efficient than search without information transfer between units. Finally, we review our recent attempts to construct and analyze simple models of true Darwinian evolutionary units in the brain in terms of connectivity and activity copying of neuronal groups. Although none of the proposed neuronal replicators include miraculous mechanisms, their identification remains a challenge but also a great promise. PMID:22557963

  9. Intersubject Variability of and Genetic Effects on the Brain's Functional Connectivity during Infancy

    PubMed Central

    Elton, Amanda; Zhu, Hongtu; Alcauter, Sarael; Smith, J. Keith; Gilmore, John H.; Lin, Weili

    2014-01-01

    Infancy is a period featuring a high level of intersubject variability but the brain basis for such variability and the potential genetic/environmental contributions remain largely unexplored. The assessment of the brain's functional connectivity during infancy by the resting state functional magnetic resonance imaging (rsfMRI) technique (Biswal et al., 1995) provides a unique means to probe the brain basis of intersubject variability during infancy. In this study, an unusually large typically developing human infant sample including 58 singletons, 132 dizygotic twins, and 98 monozygotic twins with rsfMRI scans during the first 2 years of life was recruited to delineate the spatial and temporal developmental patterns of both the intersubject variability of and genetic effects on the brain's functional connectivity. Through systematic voxelwise functional connectivity analyses, our results revealed that the intersubject variability at birth features lower variability in primary functional areas but higher values in association areas. Although the relative pattern remains largely consistent, the magnitude of intersubject variability undergoes an interesting U-shaped growth during the first 2 years of life. Overall, the intersubject variability patterns during infancy show both adult-like and infant-specific characteristics (Mueller et al., 2013). On the other hand, age-dependent genetic effects were observed showing significant but bidirectional relationships with intersubject variability. The temporal and spatial patterns of the intersubject variability of and genetic contributions to the brain's functional connectivity documented in this study shed light on the largely uncharted functional development of the brain during infancy. PMID:25143609

  10. Functional Representation of Enzymes by Specific Peptides

    PubMed Central

    Kunik, Vered; Meroz, Yasmine; Solan, Zach; Sandbank, Ben; Weingart, Uri; Ruppin, Eytan; Horn, David

    2007-01-01

    Predicting the function of a protein from its sequence is a long-standing goal of bioinformatic research. While sequence similarity is the most popular tool used for this purpose, sequence motifs may also subserve this goal. Here we develop a motif-based method consisting of applying an unsupervised motif extraction algorithm (MEX) to all enzyme sequences, and filtering the results by the four-level classification hierarchy of the Enzyme Commission (EC). The resulting motifs serve as specific peptides (SPs), appearing on single branches of the EC. In contrast to previous motif-based methods, the new method does not require any preprocessing by multiple sequence alignment, nor does it rely on over-representation of motifs within EC branches. The SPs obtained comprise on average 8.4 4.5 amino acids, and specify the functions of 93% of all enzymes, which is much higher than the coverage of 63% provided by ProSite motifs. The SP classification thus compares favorably with previous function annotation methods and successfully demonstrates an added value in extreme cases where sequence similarity fails. Interestingly, SPs cover most of the annotated active and binding site amino acids, and occur in active-site neighboring 3-D pockets in a highly statistically significant manner. The latter are assumed to have strong biological relevance to the activity of the enzyme. Further filtering of SPs by biological functional annotations results in reduced small subsets of SPs that possess very large enzyme coverage. Overall, SPs both form a very useful tool for enzyme functional classification and bear responsibility for the catalytic biological function carried out by enzymes. PMID:17722976

  11. Quetiapine modulates functional connectivity in brain aggression networks.

    PubMed

    Klasen, Martin; Zvyagintsev, Mikhail; Schwenzer, Michael; Mathiak, Krystyna A; Sarkheil, Pegah; Weber, René; Mathiak, Klaus

    2013-07-15

    Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine. PMID:23501053

  12. Human brain activity with functional NIR optical imager

    NASA Astrophysics Data System (ADS)

    Luo, Qingming

    2001-08-01

    In this paper we reviewed the applications of functional near infrared optical imager in human brain activity. Optical imaging results of brain activity, including memory for new association, emotional thinking, mental arithmetic, pattern recognition ' where's Waldo?, occipital cortex in visual stimulation, and motor cortex in finger tapping, are demonstrated. It is shown that the NIR optical method opens up new fields of study of the human population, in adults under conditions of simulated or real stress that may have important effects upon functional performance. It makes practical and affordable for large populations the complex technology of measuring brain function. It is portable and low cost. In cognitive tasks subjects could report orally. The temporal resolution could be millisecond or less in theory. NIR method will have good prospects in exploring human brain secret.

  13. Exploring Dynamic Brain Functional Networks Using Continuous "State-Related" Functional MRI.

    PubMed

    Li, Xun; Zang, Yu-Feng; Zhang, Han

    2015-01-01

    We applied a "temporal decomposition" method, which decomposed a single brain functional network into several "modes"; each of them dominated a short temporal period, on a continuous, "state-" related, "finger-force feedback" functional magnetic resonance imaging experiment. With the hypothesis that attention and internal/external information processing interaction could be manipulated by different (real and sham) feedback conditions, we investigated functional network dynamics of the "default mode," "executive control," and sensorimotor networks. They were decomposed into several modes. During real feedback, the occurrence of "default mode-executive control competition-related" mode was higher than that during sham feedback (P = 0.0003); the "default mode-visual facilitation-related" mode more frequently appeared during sham than real feedback (P = 0.0004). However, the dynamics of the sensorimotor network did not change significantly between two conditions (P > 0.05). Our results indicated that the visual-guided motor feedback involves higher cognitive functional networks rather than primary motor network. The dynamics monitoring of inner and outside environment and multisensory integration could be the mechanisms. This study is an extension of our previous region-specific and static-styled study of our brain functional architecture. PMID:26413546

  14. Cerebrospinal fluid levels of brain specific proteins in optic neuritis.

    PubMed

    Lim, E T; Grant, D; Pashenkov, M; Keir, G; Thompson, E J; Söderström, M; Giovannoni, G

    2004-06-01

    This study evaluates levels of cerebrospinal fluid (CSF) brain-specific proteins (BSP) in subjects with optic neuritis (ON) who are at high risk of progression to multiple sclerosis (MS). Forty-one subjects had acute ON and 17 subjects with other neurological diseases (OND) served as controls. Twenty-one subjects with ON had white matter lesions on magnetic resonance imaging (MRI) and intrathecal synthesis of oligoclonal IgG bands (OB) consistent with being at high risk of progression to MS; eight of whom later were diagnosed with clinically definite MS (CDMS). Levels of S100B, ferritin and two neurofilament heavy chain phosphoforms (NfH(SM134) and NfH(SM135)) were analysed using ELISA technique. A putative index of 'axonal health' was expressed as a ratio of NfH(SM134) to NfH(S135). NfH(SM134) and the NfH(SM134:SM135) were significantly elevated in subjects with ON compared to controls. No significant differences in levels of CSF BSP were seen between ON subjects with CDMS plus those at high risk of progression to MS and ON subjects with normal MRI and negative CSF analysis. In conclusion, there is evidence of axonal damage in subjects who present with ON, which is independent of the diagnosis of CDMS. PMID:15222688

  15. [Determinism and Freedom of Choice in the Brain Functioning].

    PubMed

    Ivanitsky, A M

    2015-01-01

    The problem is considered whether the brain response is completely determined by the stimulus and the personal experience or in some cases the brain is free to choose its behavioral response to achieve the desired goal. The attempt is made to approach to this important philosophical problem basing on modern knowledge about the brain. The paper consists of four parts. In the first part the theoretical views about the free choice problem solving are considered, including views about the freedom of choice as a useful illusion, the hypothesis on appliance of quantum mechanics laws to the brain functioning and the theory of mentalism. In other tree parts consequently the more complicated brain functions such as choice reaction, thinking and creation are analyzed. The general conclusion is that the possibility of quite unpredictable, but sometimes very effective decisions increases when the brain functions are more and more complicated. This fact can be explained with two factors: increasing stochasticity of the brain processes and the role of top-down determinations from mental to neural levels, according to the theory of mentalism. PMID:26601509

  16. Functional abnormalities in normally appearing athletes following mild traumatic brain injury: a functional MRI study

    PubMed Central

    Slobounov, Semyon M.; Zhang, K.; Pennell, D.; Ray, W.; Johnson, B.; Sebastianelli, W.

    2010-01-01

    Memory problems are one of the most common symptoms of sport-related mild traumatic brain injury (MTBI), known as concussion. Surprisingly, little research has examined spatial memory in concussed athletes given its importance in athletic environments. Here, we combine functional magnetic resonance imaging (fMRI) with a virtual reality (VR) paradigm designed to investigate the possibility of residual functional deficits in recently concussed but asymptomatic individuals. Specifically, we report performance of spatial memory navigation tasks in a VR environment and fMRI data in 15 athletes suffering from MTBI and 15 neurologically normal, athletically active age matched controls. No differences in performance were observed between these two groups of subjects in terms of success rate (94 and 92%) and time to complete the spatial memory navigation tasks (mean = 19.5 and 19.7 s). Whole brain analysis revealed that similar brain activation patterns were observed during both encoding and retrieval among the groups. However, concussed athletes showed larger cortical networks with additional increases in activity outside of the shared region of interest (ROI) during encoding. Quantitative analysis of blood oxygen level dependent (BOLD) signal revealed that concussed individuals had a significantly larger cluster size during encoding at parietal cortex, right dorsolateral prefrontal cortex, and right hippocampus. In addition, there was a significantly larger BOLD signal percent change at the right hippocampus. Neither cluster size nor BOLD signal percent change at shared ROIs was different between groups during retrieval. These major findings are discussed with respect to current hypotheses regarding the neural mechanism responsible for alteration of brain functions in a clinical setting. PMID:20039023

  17. Relationship Between Neurocognitive Function and Quality of Life After Whole-Brain Radiotherapy in Patients With Brain Metastasis

    SciTech Connect

    Li Jing; Bentzen, Soren M.; Li Jialiang; Renschler, Markus; Mehta, Minesh P.

    2008-05-01

    Purpose: To examine the relationship between neurocognitive function (NCF) and quality of life (QOL) in patients with brain metastases after whole-brain radiotherapy. Patients and Methods: A total of 208 patients from the whole-brain radiotherapy arm of a Phase III trial (PCI-P120-9801), who underwent regular NCF and QOL (ADL [activities of daily living] and FACT-Br [Functional Assessment of Cancer Therapy-Brain-specific]) testing, were analyzed. Spearman's rank correlation was calculated between NCF and QOL, using each patient's own data, at each time point. To test the hypothesis that NCF declines before QOL changes, the predictive effect of NCF from previous visits on QOL was studied with a linear mixed-effects model. Neurocognitive function or QOL deterioration was defined relative to each patient's own baseline. Lead or lag time, defined as NCF deterioration before or after the date of QOL decline, respectively, was computed. Results: At baseline, all NCF tests showed statistically significant correlations with ADL, which became stronger at 4 months. A similar observation was made with FACT-Br. Neurocognitive function scores from previous visits predicted ADL (p < 0.05 for seven of eight tests) or FACT-Br. Scores on all eight NCF tests deteriorated before ADL decline (net lead time 9-153 days); and scores on six of eight NCF tests deteriorated before FACT-Br (net lead time 9-82 days). Conclusions: Neurocognitive function and QOL are correlated. Neurocognitive function scores from previous visits are predictive of QOL. Neurocognitive function deterioration precedes QOL decline. The sequential association between NCF and QOL decline suggests that delaying NCF deterioration is a worthwhile treatment goal in brain metastases patients.

  18. Cerebral energy metabolism and the brain's functional network architecture: an integrative review

    PubMed Central

    Lord, Louis-David; Expert, Paul; Huckins, Jeremy F; Turkheimer, Federico E

    2013-01-01

    Recent functional magnetic resonance imaging (fMRI) studies have emphasized the contributions of synchronized activity in distributed brain networks to cognitive processes in both health and disease. The brain's ‘functional connectivity' is typically estimated from correlations in the activity time series of anatomically remote areas, and postulated to reflect information flow between neuronal populations. Although the topological properties of functional brain networks have been studied extensively, considerably less is known regarding the neurophysiological and biochemical factors underlying the temporal coordination of large neuronal ensembles. In this review, we highlight the critical contributions of high-frequency electrical oscillations in the γ-band (30 to 100 Hz) to the emergence of functional brain networks. After describing the neurobiological substrates of γ-band dynamics, we specifically discuss the elevated energy requirements of high-frequency neural oscillations, which represent a mechanistic link between the functional connectivity of brain regions and their respective metabolic demands. Experimental evidence is presented for the high oxygen and glucose consumption, and strong mitochondrial performance required to support rhythmic cortical activity in the γ-band. Finally, the implications of mitochondrial impairments and deficits in glucose metabolism for cognition and behavior are discussed in the context of neuropsychiatric and neurodegenerative syndromes characterized by large-scale changes in the organization of functional brain networks. PMID:23756687

  19. ABCD: a functional database for the avian brain.

    PubMed

    Schrott, Aniko; Kabai, Peter

    2008-01-30

    Here we present the first database developed for storing, retrieving and cross-referencing neuroscience information about the connectivity of the avian brain. The Avian Brain Circuitry Database (ABCD) contains entries about the new and old terminology of the areas and their hierarchy, data on connections between brain regions, as well as a functional keyword system linked to brain regions and connections. Data were collected from the primary literature and textbooks, and an online submission system was developed to facilitate further data collection directly from researchers. The database aims to help spread the results of avian connectivity studies, the recently revised nomenclature and also to provide data for brain network research. ABCD is freely available at http://www.behav.org/abcd. PMID:17889371

  20. Magnetoencephalography in studies of human cognitive brain function.

    PubMed

    Näätänen, R; Ilmoniemi, R J; Alho, K

    1994-09-01

    Magnetoencephalography provides a new dimension to the functional imaging of the brain. The cerebral magnetic fields recorded noninvasively enable the accurate determination of locations of cerebral activity with an uncompromized time resolution. The first whole-scalp sensor arrays have just recently come into operation, and significant advances are to be expected in both neurophysiological and cognitive studies, as well as in clinical practice. However, although the accuracy of locating isolated sources of brain activity has improved, identification of multiple simultaneous sources can still be a problem. Therefore, attempts are being made to combine magnetoencephalography with other brain-imaging methods to improve spatial localization of multiple sources and, simultaneously, to achieve a more complete characterization of different aspects of brain activity during cognitive processing. Owing to its good time resolution and considerably better spatial accuracy than that provided by EEG, magnetoencephalography holds great promise as a tool for revealing information-processing sequences of the human brain. PMID:7529443

  1. Impact of head morphology on local brain specific absorption rate from exposure to mobile phone radiation.

    PubMed

    Adibzadeh, Fatemeh; Bakker, Jurriaan F; Paulides, Margarethus M; Verhaart, René F; van Rhoon, Gerard C

    2015-01-01

    Among various possible health effects of mobile phone radiation, the risk of inducing cancer has the strongest interest of laymen and health organizations. Recently, the Interphone epidemiological study investigated the association between the estimated Radio Frequency (RF) dose from mobile phones and the risk of developing a brain tumor. Their dosimetric analysis included over 100 phone models but only two homogeneous head phantoms. So, the potential impact of individual morphological features on global and local RF absorption in the brain was not investigated. In this study, we performed detailed dosimetric simulations for 20 head models and quantified the variation of RF dose in different brain regions as a function of head morphology. Head models were exposed to RF fields from generic mobile phones at 835 and 1900 MHz in the "tilted" and "cheek" positions. To evaluate the local RF dose variation, we used and compared two different post-processing methods, that is, averaging specific absorption rate (SAR) over Talairach regions and over sixteen predefined 1 cm(3) cube-shaped field-sensors. The results show that the variation in the averaged SAR among the heads can reach up to 16.4 dB at a 1 cm(3) cube inside the brain (field-sensor method) and alternatively up to 15.8 dB in the medulla region (Talairach method). In conclusion, we show head morphology as an important uncertainty source for dosimetric studies of mobile phones. Therefore, any dosimetric analysis dealing with RF dose at a specific region in the brain (e.g., tumor risk analysis) should be based upon real morphology. PMID:25399806

  2. Functional imaging of the brain with/sup 18/F-fluorodeoxyglucose

    SciTech Connect

    Reivich, M; Greenberg, J; Alavi, A; Hand, P; Rintelmann, W; Rosenquist, A; Christman, D; Fowler, J; MacGregor, R; Wolf, A

    1980-01-01

    A techniques is reported by which it is possible to determine which regions of the human brain become functionally active in response to a specific stimulus. The method utilizes /sup 18/F-2-fluoro-2-deoxyglucose ((/sup 18/F)-FDG) administered as a bolus. (/sup 18/F)-FDG is used as a tracer for the exchange of glucose between plasma and brain and its phosphorylation. The subject is then scanned during administration of a physiologic stimulus by position emission tomography and the three-dimensional distribution of /sup 18/F activity in the brain determined. (ACR)

  3. Human brain functional MRI and DTI visualization with virtual reality

    PubMed Central

    Chen, Bin; Moreland, John; Zhang, Jingyu

    2011-01-01

    Magnetic resonance diffusion tensor imaging (DTI) and functional MRI (fMRI) are two active research areas in neuroimaging. DTI is sensitive to the anisotropic diffusion of water exerted by its macromolecular environment and has been shown useful in characterizing structures of ordered tissues such as the brain white matter, myocardium, and cartilage. The diffusion tensor provides two new types of information of water diffusion: the magnitude and the spatial orientation of water diffusivity inside the tissue. This information has been used for white matter fiber tracking to review physical neuronal pathways inside the brain. Functional MRI measures brain activations using the hemodynamic response. The statistically derived activation map corresponds to human brain functional activities caused by neuronal activities. The combination of these two methods provides a new way to understand human brain from the anatomical neuronal fiber connectivity to functional activities between different brain regions. In this study, virtual reality (VR) based MR DTI and fMRI visualization with high resolution anatomical image segmentation and registration, ROI definition and neuronal white matter fiber tractography visualization and fMRI activation map integration is proposed. Rationale and methods for producing and distributing stereoscopic videos are also discussed. PMID:23256049

  4. Changes in functional brain organization and behavioral correlations after rehabilitative therapy using a brain-computer interface

    PubMed Central

    Young, Brittany M.; Nigogosyan, Zack; Walton, Léo M.; Song, Jie; Nair, Veena A.; Grogan, Scott W.; Tyler, Mitchell E.; Edwards, Dorothy F.; Caldera, Kristin; Sattin, Justin A.; Williams, Justin C.; Prabhakaran, Vivek

    2014-01-01

    This study aims to examine the changes in task-related brain activity induced by rehabilitative therapy using brain-computer interface (BCI) technologies and whether these changes are relevant to functional gains achieved through the use of these therapies. Stroke patients with persistent upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device (n = 8) or no therapy (n = 6). Behavioral assessments using the Stroke Impact Scale, the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT) as well as task-based fMRI scans were conducted before, during, after, and 1 month after therapy administration or at analogous intervals in the absence of therapy. Laterality Index (LI) values during finger tapping of each hand were calculated for each time point and assessed for correlation with behavioral outcomes. Brain activity during finger tapping of each hand shifted over the course of BCI therapy, but not in the absence of therapy, to greater involvement of the non-lesioned hemisphere (and lesser involvement of the stroke-lesioned hemisphere) as measured by LI. Moreover, changes from baseline LI values during finger tapping of the impaired hand were correlated with gains in both objective and subjective behavioral measures. These findings suggest that the administration of interventional BCI therapy can induce differential changes in brain activity patterns between the lesioned and non-lesioned hemispheres and that these brain changes are associated with changes in specific motor functions. PMID:25076886

  5. Functional neuroimaging of traumatic brain injury: advances and clinical utility

    PubMed Central

    Irimia, Andrei; Van Horn, John Darrell

    2015-01-01

    Functional deficits due to traumatic brain injury (TBI) can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimaging studies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. PMID:26396520

  6. Magnetic resonance and the human brain: anatomy, function and metabolism.

    PubMed

    Talos, I-F; Mian, A Z; Zou, K H; Hsu, L; Goldberg-Zimring, D; Haker, S; Bhagwat, J G; Mulkern, R V

    2006-05-01

    The introduction and development, over the last three decades, of magnetic resonance (MR) imaging and MR spectroscopy technology for in vivo studies of the human brain represents a truly remarkable achievement, with enormous scientific and clinical ramifications. These effectively non-invasive techniques allow for studies of the anatomy, the function and the metabolism of the living human brain. They have allowed for new understandings of how the healthy brain works and have provided insights into the mechanisms underlying multiple disease processes which affect the brain. Different MR techniques have been developed for studying anatomy, function and metabolism. The primary focus of this review is to describe these different methodologies and to briefly review how they are being employed to more fully appreciate the intricacies associated with the organ, which most distinctly differentiates the human species from the other animal forms on earth. PMID:16568243

  7. Resiliency of EEG-Based Brain Functional Networks.

    PubMed

    Jalili, Mahdi

    2015-01-01

    Applying tools available in network science and graph theory to study brain networks has opened a new era in understanding brain mechanisms. Brain functional networks extracted from EEG time series have been frequently studied in health and diseases. In this manuscript, we studied failure resiliency of EEG-based brain functional networks. The network structures were extracted by analysing EEG time series obtained from 30 healthy subjects in resting state eyes-closed conditions. As the network structure was extracted, we measured a number of metrics related to their resiliency. In general, the brain networks showed worse resilient behaviour as compared to corresponding random networks with the same degree sequences. Brain networks had higher vulnerability than the random ones (P < 0.05), indicating that their global efficiency (i.e., communicability between the regions) is more affected by removing the important nodes. Furthermore, the breakdown happened as a result of cascaded failures in brain networks was severer (i.e., less nodes survived) as compared to randomized versions (P < 0.05). These results suggest that real EEG-based networks have not been evolved to possess optimal resiliency against failures. PMID:26295341

  8. Hubs of brain functional networks are radically reorganized in comatose patients.

    PubMed

    Achard, Sophie; Delon-Martin, Chantal; Vértes, Petra E; Renard, Félix; Schenck, Maleka; Schneider, Francis; Heinrich, Christian; Kremer, Stéphane; Bullmore, Edward T

    2012-12-11

    Human brain networks have topological properties in common with many other complex systems, prompting the following question: what aspects of brain network organization are critical for distinctive functional properties of the brain, such as consciousness? To address this question, we used graph theoretical methods to explore brain network topology in resting state functional MRI data acquired from 17 patients with severely impaired consciousness and 20 healthy volunteers. We found that many global network properties were conserved in comatose patients. Specifically, there was no significant abnormality of global efficiency, clustering, small-worldness, modularity, or degree distribution in the patient group. However, in every patient, we found evidence for a radical reorganization of high degree or highly efficient "hub" nodes. Cortical regions that were hubs of healthy brain networks had typically become nonhubs of comatose brain networks and vice versa. These results indicate that global topological properties of complex brain networks may be homeostatically conserved under extremely different clinical conditions and that consciousness likely depends on the anatomical location of hub nodes in human brain networks. PMID:23185007

  9. Chemotherapy altered brain functional connectivity in women with breast cancer: a pilot study.

    PubMed

    Dumas, Julie A; Makarewicz, Jenna; Schaubhut, Geoffrey J; Devins, Robert; Albert, Kimberly; Dittus, Kim; Newhouse, Paul A

    2013-12-01

    Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, 1 month after, and 1 year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity 1 month after chemotherapy that partially returned to baseline at 1 year in the dorsal attention network. Decreased connectivity was seen in the default mode network at 1 month and 1 year following chemotherapy. In addition, increased subjective memory complaints were noted at 1 month and 1 year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment. PMID:23852814

  10. Democratic reinforcement: A principle for brain function

    NASA Astrophysics Data System (ADS)

    Stassinopoulos, Dimitris; Bak, Per

    1995-05-01

    We introduce a simple ``toy'' brain model. The model consists of a set of randomly connected, or layered integrate-and-fire neurons. Inputs to and outputs from the environment are connected randomly to subsets of neurons. The connections between firing neurons are strengthened or weakened according to whether the action was successful or not. Unlike previous reinforcement learning algorithms, the feedback from the environment is democratic: it affects all neurons in the same way, irrespective of their position in the network and independent of the output signal. Thus no unrealistic back propagation or other external computation is needed. This is accomplished by a global threshold regulation which allows the system to self-organize into a highly susceptible, possibly ``critical'' state with low activity and sparse connections between firing neurons. The low activity permits memory in quiescent areas to be conserved since only firing neurons are modified when new information is being taught.

  11. Functional connectome fingerprinting: identifying individuals using patterns of brain connectivity.

    PubMed

    Finn, Emily S; Shen, Xilin; Scheinost, Dustin; Rosenberg, Monica D; Huang, Jessica; Chun, Marvin M; Papademetris, Xenophon; Constable, R Todd

    2015-11-01

    Functional magnetic resonance imaging (fMRI) studies typically collapse data from many subjects, but brain functional organization varies between individuals. Here we establish that this individual variability is both robust and reliable, using data from the Human Connectome Project to demonstrate that functional connectivity profiles act as a 'fingerprint' that can accurately identify subjects from a large group. Identification was successful across scan sessions and even between task and rest conditions, indicating that an individual's connectivity profile is intrinsic, and can be used to distinguish that individual regardless of how the brain is engaged during imaging. Characteristic connectivity patterns were distributed throughout the brain, but the frontoparietal network emerged as most distinctive. Furthermore, we show that connectivity profiles predict levels of fluid intelligence: the same networks that were most discriminating of individuals were also most predictive of cognitive behavior. Results indicate the potential to draw inferences about single subjects on the basis of functional connectivity fMRI. PMID:26457551

  12. Early Bifrontal Brain Injury: Disturbances in Cognitive Function Development

    PubMed Central

    Bonnier, Christine; Costet, Aurélie; Hmaimess, Ghassan; Catale, Corinne; Maillart, Christelle; Marique, Patricia

    2010-01-01

    We describe six psychomotor, language, and neuropsychological sequential developmental evaluations in a boy who sustained a severe bifrontal traumatic brain injury (TBI) at 19 months of age. Visuospatial, drawing, and writing skills failed to develop normally. Gradually increasing difficulties were noted in language leading to reading and spontaneous speech difficulties. The last two evaluations showed executive deficits in inhibition, flexibility, and working memory. Those executive abnormalities seemed to be involved in the other impairments. In conclusion, early frontal brain injury disorganizes the development of cognitive functions, and interactions exist between executive function and other cognitive functions during development. PMID:21188227

  13. Patient-specific computational biomechanics of the brain without segmentation and meshing.

    PubMed

    Zhang, Johnny Y; Joldes, Grand Roman; Wittek, Adam; Miller, Karol

    2013-02-01

    Motivated by patient-specific computational modelling in the context of image-guided brain surgery, we propose a new fuzzy mesh-free modelling framework. The method works directly on an unstructured cloud of points that do not form elements so that mesh generation is not required. Mechanical properties are assigned directly to each integration point based on fuzzy tissue classification membership functions without the need for image segmentation. Geometric integration is performed over an underlying uniform background grid. The verification example shows that, while requiring no hard segmentation and meshing, the proposed model gives, for all practical purposes, equivalent results to a finite element model. PMID:23345159

  14. Organization of Cognitive Functions in the Brain.

    ERIC Educational Resources Information Center

    Smith, Aaron

    Neuropsychological research on the effects of hemispherectomy-the excision of one of the cerebral hemispheres-in children and adults adds to knowledge about the division of labor between the left cerebral hemisphere, which specializes in language and verbal cognitive functions, and the right hemisphere, which specializes in nonlanguage functions.…

  15. How the brain attunes to sentence processing: Relating behavior, structure, and function.

    PubMed

    Fengler, Anja; Meyer, Lars; Friederici, Angela D

    2016-04-01

    Unlike other aspects of language comprehension, the ability to process complex sentences develops rather late in life. Brain maturation as well as verbal working memory (vWM) expansion have been discussed as possible reasons. To determine the factors contributing to this functional development, we assessed three aspects in different age-groups (5-6years, 7-8years, and adults): first, functional brain activity during the processing of increasingly complex sentences; second, brain structure in language-related ROIs; and third, the behavioral comprehension performance on complex sentences and the performance on an independent vWM test. At the whole-brain level, brain functional data revealed a qualitatively similar neural network in children and adults including the left pars opercularis (PO), the left inferior parietal lobe together with the posterior superior temporal gyrus (IPL/pSTG), the supplementary motor area, and the cerebellum. While functional activation of the language-related ROIs PO and IPL/pSTG predicted sentence comprehension performance for all age-groups, only adults showed a functional selectivity in these brain regions with increased activation for more complex sentences. The attunement of both the PO and IPL/pSTG toward a functional selectivity for complex sentences is predicted by region-specific gray matter reduction while that of the IPL/pSTG is additionally predicted by vWM span. Thus, both structural brain maturation and vWM expansion provide the basis for the emergence of functional selectivity in language-related brain regions leading to more efficient sentence processing during development. PMID:26777477

  16. How the brain attunes to sentence processing: Relating behavior, structure, and function

    PubMed Central

    Fengler, Anja; Meyer, Lars; Friederici, Angela D.

    2016-01-01

    Unlike other aspects of language comprehension, the ability to process complex sentences develops rather late in life. Brain maturation as well as verbal working memory (vWM) expansion have been discussed as possible reasons. To determine the factors contributing to this functional development, we assessed three aspects in different age-groups (5–6 years, 7–8 years, and adults): first, functional brain activity during the processing of increasingly complex sentences; second, brain structure in language-related ROIs; and third, the behavioral comprehension performance on complex sentences and the performance on an independent vWM test. At the whole-brain level, brain functional data revealed a qualitatively similar neural network in children and adults including the left pars opercularis (PO), the left inferior parietal lobe together with the posterior superior temporal gyrus (IPL/pSTG), the supplementary motor area, and the cerebellum. While functional activation of the language-related ROIs PO and IPL/pSTG predicted sentence comprehension performance for all age-groups, only adults showed a functional selectivity in these brain regions with increased activation for more complex sentences. The attunement of both the PO and IPL/pSTG toward a functional selectivity for complex sentences is predicted by region-specific gray matter reduction while that of the IPL/pSTG is additionally predicted by vWM span. Thus, both structural brain maturation and vWM expansion provide the basis for the emergence of functional selectivity in language-related brain regions leading to more efficient sentence processing during development. PMID:26777477

  17. Function-Structure Associations of the Brain: Evidence from Multimodal Connectivity and Covariance Studies

    PubMed Central

    Sui, Jing; Huster, Rene; Yu, Qingbao; Segall, Judith M.; Calhoun, Vince D

    2013-01-01

    Despite significant advances in multimodal imaging techniques and analysis approaches, unimodal studies are still the predominant way to investigate brain changes or group differences, including structural magnetic resonance imaging (sMRI), functional MRI (fMRI), diffusion tensor imaging (DTI) and electroencephalography (EEG). Multimodal brain studies can be used to understand the complex interplay of anatomical, functional and physiological brain alterations or development, and to better comprehend the biological significance of multiple imaging measures. To examine the function-structure associations of the brain in a more comprehensive and integrated manner, we reviewed a number of multimodal studies that combined two or more functional (fMRI and/or EEG) and structural (sMRI and/or DTI) modalities. In this review paper, we specifically focused on multimodal neuroimaging studies on cognition, aging, disease and behavior. We also compared multiple analysis approaches, including univariate and multivariate methods. The possible strengths and limitations of each method are highlighted, which can guide readers when selecting a method based on a given research question. In particular, we believe that multimodal fusion approaches will shed further light on the neuronal mechanisms underlying the major structural and functional pathophysiological features of both the healthy brain (e.g. development) or the diseased brain (e.g. mental illness). And in the latter case, may provide a more sensitive measure than unimodal imaging for disease classification, e.g. multimodal biomarkers, which potentially can be used to support clinical diagnosis based on neuroimaging techniques. PMID:24084066

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

    PubMed Central

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

    2013-01-01

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

  19. Altered host behaviour and brain serotonergic activity caused by acanthocephalans: evidence for specificity

    PubMed Central

    Tain, Luke; Perrot-Minnot, Marie-Jeanne; Cézilly, Frank

    2006-01-01

    Manipulative parasites can alter the phenotype of intermediate hosts in various ways. However, it is unclear whether such changes are just by-products of infection or adaptive and enhance transmission to the final host. Here, we show that the alteration of serotonergic activity is functionally linked to the alteration of specific behaviour in the amphipod Gammarus pulex infected with acanthocephalan parasites. Pomphorhynchus laevis and, to a lesser extent, Pomphorhynchus tereticollis altered phototactism, but not geotactism, in G. pulex, whereas the reverse was true for Polymorphus minutus. Serotonin (5-hydroxytryptamine, 5-HT) injected to uninfected G. pulex mimicked the altered phototactism, but had no effect on geotactism. Photophilic G. pulex infected with P. laevis or P. tereticollis showed a 40% increase in brain 5-HT immunoreactivity compared to photophobic, uninfected individuals. In contrast, brain 5-HT immunoreactivity did not differ between P. minutus-infected and uninfected G. pulex. Finally, brain 5-HT immunoreactivity differed significantly among P. tereticollis-infected individuals in accordance with their degree of manipulation. Our results demonstrate that altered 5-HT activity is not the mere consequence of infection by acanthocephalans but is specifically linked to the disruption of host photophobic behaviour, whereas the alteration of other behaviours such as geotactism may rely on distinct physiological routes. PMID:17015346

  20. Region-specific changes in presynaptic agmatine and glutamate levels in the aged rat brain.

    PubMed

    Jing, Y; Liu, P; Leitch, B

    2016-01-15

    During the normal aging process, the brain undergoes a range of biochemical and structural alterations, which may contribute to deterioration of sensory and cognitive functions. Age-related deficits are associated with altered efficacy of synaptic neurotransmission. Emerging evidence indicates that levels of agmatine, a putative neurotransmitter in the mammalian brain, are altered in a region-specific manner during the aging process. The gross tissue content of agmatine in the prefrontal cortex (PFC) of aged rat brains is decreased whereas levels in the temporal cortex (TE) are increased. However, it is not known whether these changes in gross tissue levels are also mirrored by changes in agmatine levels at synapses and thus could potentially contribute to altered synaptic function with age. In the present study, agmatine levels in presynaptic terminals in the PFC and TE regions (300 terminals/region) of young (3month; n=3) and aged (24month; n=3) brains of male Sprague-Dawley rats were compared using quantitative post-embedding immunogold electron-microscopy. Presynaptic levels of agmatine were significantly increased in the TE region (60%; p<0.001) of aged rats compared to young rats, however no significant differences were detected in synaptic levels in the PFC region. Double immunogold labeling indicated that agmatine and glutamate were co-localized in the same synaptic terminals, and quantitative analyses revealed significantly reduced glutamate levels in agmatine-immunopositive synaptic terminals in both regions in aged rats compared to young animals. This study, for the first time, demonstrates differential effects of aging on agmatine and glutamate in the presynaptic terminals of PFC and TE. Future research is required to understand the functional significance of these changes and the underlying mechanisms. PMID:26548412

  1. Specific binding of naloxone to ovine brain tissue: comparison of brain regions and endocrine states.

    PubMed

    Weesner, G D; Trout, W E; Malven, P V

    1989-06-01

    Binding of [3H]naloxone ([3H]NAL) to brain membranes was quantified by Scatchard analysis using two methods of separating bound from free [3H]NAL. In the centrifugation method, membranes that were soluble at 1,000 x g, but sedimented at 20,000 x g, were incubated with [3H]NAL. For filtration, all membranes that sedimented at 20,000 x g were incubated and filtered through glass filter fibers. Nonspecific binding was estimated using greater than 500-fold excess of unlabeled naloxone (10(-6) M). Specific binding of [3H]NAL was used to generate linear multiple-point Scatchard plots, which indicated a single class of high-affinity sites. In Exp. 1, 10 ovariectomized (OVX) ewes were injected with estradiol-17 beta alone or in combination with progesterone. Compared with OVX controls, these hormonal treatments did not affect binding of [3H]NAL (centrifugation method) to combined hypothalamus (HYP) + preoptic (POA) tissues. In cyclic ewes (Exp. 2, filtration method), affinity constants (2.4 +/- .2 x 10(8) M-1) did not differ among HYP, POA and basal forebrain (BF) tissues, but BF had more sites (39 +/- 3 fmol/mg) than either HYP (14 +/- 1) or POA (17 +/- 1). Binding affinity and concentration of sites within each brain area (HYP, POA, BF) did not differ between d 8 and d 16 (preovulatory but after luteolysis) in normally cycling ewes. Overall, neural tissue dissected from BF had a greater concentration of binding sites than HYP or POA. Exogenous and endogenous fluctuations in ovarian steroids did not affect binding of [3H]NAL to these tissues. PMID:2768110

  2. Loss of brain function - liver disease

    MedlinePlus

    ... may be made by the body, such as ammonia. Or they may be substances that you take ... MRI EEG Liver function tests Prothrombin time Serum ammonia level Sodium level in the blood Potassium level ...

  3. Analyzing complex functional brain networks: Fusing statistics and network science to understand the brain*†

    PubMed Central

    Simpson, Sean L.; Bowman, F. DuBois; Laurienti, Paul J.

    2014-01-01

    Complex functional brain network analyses have exploded over the last decade, gaining traction due to their profound clinical implications. The application of network science (an interdisciplinary offshoot of graph theory) has facilitated these analyses and enabled examining the brain as an integrated system that produces complex behaviors. While the field of statistics has been integral in advancing activation analyses and some connectivity analyses in functional neuroimaging research, it has yet to play a commensurate role in complex network analyses. Fusing novel statistical methods with network-based functional neuroimage analysis will engender powerful analytical tools that will aid in our understanding of normal brain function as well as alterations due to various brain disorders. Here we survey widely used statistical and network science tools for analyzing fMRI network data and discuss the challenges faced in filling some of the remaining methodological gaps. When applied and interpreted correctly, the fusion of network scientific and statistical methods has a chance to revolutionize the understanding of brain function. PMID:25309643

  4. Understanding entangled cerebral networks: a prerequisite for restoring brain function with brain-computer interfaces

    PubMed Central

    Mandonnet, Emmanuel; Duffau, Hugues

    2014-01-01

    Historically, cerebral processing has been conceptualized as a framework based on statically localized functions. However, a growing amount of evidence supports a hodotopical (delocalized) and flexible organization. A number of studies have reported absence of a permanent neurological deficit after massive surgical resections of eloquent brain tissue. These results highlight the tremendous plastic potential of the brain. Understanding anatomo-functional correlates underlying this cerebral reorganization is a prerequisite to restore brain functions through brain-computer interfaces (BCIs) in patients with cerebral diseases, or even to potentiate brain functions in healthy individuals. Here, we review current knowledge of neural networks that could be utilized in the BCIs that enable movements and language. To this end, intraoperative electrical stimulation in awake patients provides valuable information on the cerebral functional maps, their connectomics and plasticity. Overall, these studies indicate that the complex cerebral circuitry that underpins interactions between action, cognition and behavior should be throughly investigated before progress in BCI approaches can be achieved. PMID:24834030

  5. Stereotactic PET atlas of the human brain: Aid for visual interpretation of functional brain images

    SciTech Connect

    Minoshima, S.; Koeppe, R.A.; Frey, A.; Ishihara, M.; Kuhl, D.E.

    1994-06-01

    In the routine analysis of functional brain images obtained by PET, subjective visual interpretation is often used for anatomic localization. To enhance the accuracy and consistency of the anatomic interpretation, a PET stereotactic atlas and localization approach was designed for functional brain images. The PET atlas was constructed from a high-resolution [{sup 18}F]fluorodeoxyglucose (FDG) image set of a normal volunteer (a 41-yr-ld woman). The image set was reoriented stereotactically, according to the intercommissural (anterior and posterior commissures) line and transformed to the standard stereotactic atlas coordinates. Cerebral structures were annotated on the transaxial planes using a proportional grid system and surface-rendered images. The stereotactic localization technique was applied to image sets from patients with Alzheimer`s disease, and areas of functional alteration were localized visually by referring to the PET atlas. Major brain structures were identified on both transaxial planes and surface-rendered images. In the stereotactic system, anatomic correspondence between the PET atlas and stereotactically reoriented individual image sets of patients with Alzheimer`s disease facilitated both indirect and direct localization of the cerebral structures. Because rapid stereotactic alignment methods for PET images are now available for routine use, the PET atlas will serve as an aid for visual interpretation of functional brain images in the stereotactic system. Widespread application of stereotactic localization may be used in functional brain images, not only in the research setting, but also in routine clinical situations. 41 refs., 3 figs.

  6. Fluid intelligence and brain functional organization in aging yoga and meditation practitioners

    PubMed Central

    Gard, Tim; Taquet, Maxime; Dixit, Rohan; Hölzel, Britta K.; de Montjoye, Yves-Alexandre; Brach, Narayan; Salat, David H.; Dickerson, Bradford C.; Gray, Jeremy R.; Lazar, Sara W.

    2014-01-01

    Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation. PMID:24795629

  7. Fluid intelligence and brain functional organization in aging yoga and meditation practitioners.

    PubMed

    Gard, Tim; Taquet, Maxime; Dixit, Rohan; Hölzel, Britta K; de Montjoye, Yves-Alexandre; Brach, Narayan; Salat, David H; Dickerson, Bradford C; Gray, Jeremy R; Lazar, Sara W

    2014-01-01

    Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation. PMID:24795629

  8. Brain Region-Specific Expression of MeCP2 Isoforms Correlates with DNA Methylation within Mecp2 Regulatory Elements

    PubMed Central

    Liyanage, Vichithra R. B.; Rastegar, Mojgan

    2014-01-01

    MeCP2 is a critical epigenetic regulator in brain and its abnormal expression or compromised function leads to a spectrum of neurological disorders including Rett Syndrome and autism. Altered expression of the two MeCP2 isoforms, MeCP2E1 and MeCP2E2 has been implicated in neurological complications. However, expression, regulation and functions of the two isoforms are largely uncharacterized. Previously, we showed the role of MeCP2E1 in neuronal maturation and reported MeCP2E1 as the major protein isoform in the adult mouse brain, embryonic neurons and astrocytes. Recently, we showed that DNA methylation at the regulatory elements (REs) within the Mecp2 promoter and intron 1 impact the expression of Mecp2 isoforms in differentiating neural stem cells. This current study is aimed for a comparative analysis of temporal, regional and cell type-specific expression of MeCP2 isoforms in the developing and adult mouse brain. MeCP2E2 displayed a later expression onset than MeCP2E1 during mouse brain development. In the adult female and male brain hippocampus, both MeCP2 isoforms were detected in neurons, astrocytes and oligodendrocytes. Furthermore, MeCP2E1 expression was relatively uniform in different brain regions (olfactory bulb, striatum, cortex, hippocampus, thalamus, brainstem and cerebellum), whereas MeCP2E2 showed differential enrichment in these brain regions. Both MeCP2 isoforms showed relatively similar distribution in these brain regions, except for cerebellum. Lastly, a preferential correlation was observed between DNA methylation at specific CpG dinucleotides within the REs and Mecp2 isoform-specific expression in these brain regions. Taken together, we show that MeCP2 isoforms display differential expression patterns during brain development and in adult mouse brain regions. DNA methylation patterns at the Mecp2 REs may impact this differential expression of Mecp2/MeCP2 isoforms in brain regions. Our results significantly contribute towards characterizing the expression profiles of Mecp2/MeCP2 isoforms and thereby provide insights on the potential role of MeCP2 isoforms in the developing and adult brain. PMID:24594659

  9. Laterality patterns of brain functional connectivity: gender effects.

    PubMed

    Tomasi, Dardo; Volkow, Nora D

    2012-06-01

    Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism). PMID:21878483

  10. Linking structure and function: Information processing in the brain

    SciTech Connect

    Gremillion, M.A.V.

    1990-01-01

    Traditionally, theories of function in neuroscience have emerged from physiology. Physiologists have suggested a number of means by which information in the brain can be processed, yet the principles underlying the generation of these phenomena are not well understood. A complex systems approach would be to examine the overall structure and function of the system and to attempt to establish a common framework for information processing interactions. This paper will use the structure-function relationship as a basis for exploring units of information processing. It will examine the brain as a whole, first providing the non-specialists with an short overview of the structure and some of the functions or outputs of the brain. It then very briefly reviews three of the prominent theoretical concepts that have emerged in the last few decades: receptive fields, feature extraction, and parallel processing. Next, it addresses the question of information processing and outlines the structures which have traditionally been proposed to be the basic unit of information processing. An alternative unit on which information processing in the brain might be based is then proposed, and data outlined to support it. Finally, the implications of this different mode of processing are discussed, both for the brain and for other complex systems. 40 refs., 4 figs., 2 tabs.

  11. An Adaptive Complex Network Model for Brain Functional Networks

    PubMed Central

    Gomez Portillo, Ignacio J.; Gleiser, Pablo M.

    2009-01-01

    Brain functional networks are graph representations of activity in the brain, where the vertices represent anatomical regions and the edges their functional connectivity. These networks present a robust small world topological structure, characterized by highly integrated modules connected sparsely by long range links. Recent studies showed that other topological properties such as the degree distribution and the presence (or absence) of a hierarchical structure are not robust, and show different intriguing behaviors. In order to understand the basic ingredients necessary for the emergence of these complex network structures we present an adaptive complex network model for human brain functional networks. The microscopic units of the model are dynamical nodes that represent active regions of the brain, whose interaction gives rise to complex network structures. The links between the nodes are chosen following an adaptive algorithm that establishes connections between dynamical elements with similar internal states. We show that the model is able to describe topological characteristics of human brain networks obtained from functional magnetic resonance imaging studies. In particular, when the dynamical rules of the model allow for integrated processing over the entire network scale-free non-hierarchical networks with well defined communities emerge. On the other hand, when the dynamical rules restrict the information to a local neighborhood, communities cluster together into larger ones, giving rise to a hierarchical structure, with a truncated power law degree distribution. PMID:19738902

  12. Neuron-glia networks: integral gear of brain function

    PubMed Central

    Perea, Gertrudis; Sur, Mriganka; Araque, Alfonso

    2014-01-01

    Astrocytes, the most abundant glial cell in the brain, play critical roles in metabolic and homeostatic functions of the Nervous System; however, their participation in coding information and cognitive processes has been largely ignored. The strategic position of astrocyte processes facing synapses and the astrocyte ability to uptake neurotransmitters and release neuroactive substances, so-called “gliotransmitters”, provide the scenario for prolific neuron-astrocyte signaling. From studies at single-cell level to animal behavior, recent advances in technology and genetics have revealed the impact of astrocyte activity in brain function from cellular and synaptic physiology, neuronal circuits to behavior. The present review critically discusses the consequences of astrocyte signaling on synapses and networks, as well as its impact on neuronal information processing, showing that some crucial brain functions arise from the coordinated activity of neuron-glia networks. PMID:25414643

  13. Assortative mixing in functional brain networks during epileptic seizures

    NASA Astrophysics Data System (ADS)

    Bialonski, Stephan; Lehnertz, Klaus

    2013-09-01

    We investigate assortativity of functional brain networks before, during, and after one-hundred epileptic seizures with different anatomical onset locations. We construct binary functional networks from multi-channel electroencephalographic data recorded from 60 epilepsy patients; and from time-resolved estimates of the assortativity coefficient, we conclude that positive degree-degree correlations are inherent to seizure dynamics. While seizures evolve, an increasing assortativity indicates a segregation of the underlying functional network into groups of brain regions that are only sparsely interconnected, if at all. Interestingly, assortativity decreases already prior to seizure end. Together with previous observations of characteristic temporal evolutions of global statistical properties and synchronizability of epileptic brain networks, our findings may help to gain deeper insights into the complicated dynamics underlying generation, propagation, and termination of seizures.

  14. The brain and higher mental function.

    PubMed

    Smith, G C

    1991-06-01

    Critical evaluation of biological theories of psychiatric disorder requires an understanding of current concepts of higher mental function and its related biology. Both the nature of the topic and the rapidity of advances in the field make it difficult to obtain an updated synthesis. Part I of this paper attempts to provide that by reviewing current concepts of the mind/body relationship, emotion, arousal, attention, consciousness and motivation. Part II considers those concepts in relation to recent work on the structure and function of the reticular, limbic and anterior cerebral systems. It is concluded that the model of the limbic system as subserving emotional life could now perhaps be set aside in favour of the model of a core set of chemically identified neurons in the reticular system being necessary but not sufficient to subserve higher mental function whilst also subserving other integrating functions for which no mental terminology is required. The problem of developing an eclectic theory of higher mental function that will embrace these concepts is discussed. PMID:1678938

  15. Specific absorbed fractions of energy from internal photon sources in brain tumor and cerebrospinal fluid

    SciTech Connect

    Evans, J.F. )); Stubbs, J.B. )

    1995-03-01

    Transferrin, radiolabeled with In-111, can be coinjected into glioblastoma multiforme lesions, and subsequent scintigraphic imaging can demonstrate the biokinetics of the cytotoxic transferrin. The administration of [sup 111]In transferrin into a brain tumor results in distribution of radioactivity in the brain, brain tumor, and the cerebrospinal fluid (CSF). Information about absorbed radiation doses to these regions, as well as other nearby tissues and organs, is important for evaluating radiation-related risks from this procedure. The radiation dose is usually estimated for a mathematical representation of the human body. We have included source/target regions for the eye, lens of the eye, spinal column, spinal CSF, cranial CSF, and a 100-g tumor within the brain of an adult male phantom developed by Cristy and Eckerman. The spinal column, spinal CSF, and the eyes have not been routinely included in photon transport simulations. Specific absorbed fractions (SAFs) as a function of photon energy were calculated using the ALGAMP computer code, which utilizes Monte Carlo techniques for simulating photon transport. The ALGAMP code was run three times, with the source activity distributed uniformly within the tumor, cranial CSF, and the spinal CSF volumes. These SAFs, which were generated for 12 discrete photon energies ranging from 0.01 to 4.0 MeV, were used with decay scheme data to calculate [ital S]-values needed for estimating absorbed doses. [ital S]-values for [sup 111]In are given for three source regions (brain tumor, cranial CSF, and spinal CSF) and all standard target regions/organs, the eye and lens, as well as to tissues within these source regions. [ital S]-values for the skeletal regions containing active marrow are estimated. These results are useful in evaluating the radiation doses from intracranial administration of [sup 111]In transferrin.

  16. Functional brain regeneration in the acoel worm Symsagittifera roscoffensis.

    PubMed

    Sprecher, Simon G; Bernardo-Garcia, F Javier; van Giesen, Lena; Hartenstein, Volker; Reichert, Heinrich; Neves, Ricardo; Bailly, Xavier; Martinez, Pedro; Brauchle, Michael

    2015-01-01

    The ability of some animals to regrow their head and brain after decapitation provides a striking example of the regenerative capacity within the animal kingdom. The acoel worm Symsagittifera roscoffensis can regrow its head, brain and sensory head organs within only a few weeks after decapitation. How rapidly and to what degree it also reacquires its functionality to control behavior however remains unknown. We provide here a neuroanatomical map of the brain neuropils of the adult S. roscoffensis and show that after decapitation a normal neuroanatomical organization of the brain is restored in the majority of animals. By testing different behaviors we further show that functionality of both sensory perception and the underlying brain architecture are restored within weeks after decapitation. Interestingly not all behaviors are restored at the same speed and to the same extent. While we find that phototaxis recovered rapidly, geotaxis is not restored within 7 weeks. Our findings show that regeneration of the head, sensory organs and brain result in the restoration of directed navigation behavior, suggesting a tight coordination in the regeneration of certain sensory organs with that of their underlying neural circuits. Thus, at least in S. roscoffensis, the regenerative capacity of different sensory modalities follows distinct paths. PMID:26581588

  17. Functional brain regeneration in the acoel worm Symsagittifera roscoffensis

    PubMed Central

    Sprecher, Simon G.; Bernardo-Garcia, F. Javier; van Giesen, Lena; Hartenstein, Volker; Reichert, Heinrich; Neves, Ricardo; Bailly, Xavier; Martinez, Pedro; Brauchle, Michael

    2015-01-01

    ABSTRACT The ability of some animals to regrow their head and brain after decapitation provides a striking example of the regenerative capacity within the animal kingdom. The acoel worm Symsagittifera roscoffensis can regrow its head, brain and sensory head organs within only a few weeks after decapitation. How rapidly and to what degree it also reacquires its functionality to control behavior however remains unknown. We provide here a neuroanatomical map of the brain neuropils of the adult S. roscoffensis and show that after decapitation a normal neuroanatomical organization of the brain is restored in the majority of animals. By testing different behaviors we further show that functionality of both sensory perception and the underlying brain architecture are restored within weeks after decapitation. Interestingly not all behaviors are restored at the same speed and to the same extent. While we find that phototaxis recovered rapidly, geotaxis is not restored within 7 weeks. Our findings show that regeneration of the head, sensory organs and brain result in the restoration of directed navigation behavior, suggesting a tight coordination in the regeneration of certain sensory organs with that of their underlying neural circuits. Thus, at least in S. roscoffensis, the regenerative capacity of different sensory modalities follows distinct paths. PMID:26581588

  18. Identification of subject specific and functional consistent ROIs using semi-supervised learning

    NASA Astrophysics Data System (ADS)

    Du, Yuhui; Li, Hongming; Wu, Hong; Fan, Yong

    2012-02-01

    Regions of interests (ROIs) for defining nodes of brain network are of great importance in brain network analysis of fMRI data. The ROIs are typically identified using prior anatomical information, seed region based correlation analysis, clustering analysis, region growing or ICA based methods. In this paper, we propose a novel method to identify subject specific and functional consistent ROIs for brain network analysis using semi-supervised learning. Specifically, a graph theory based semi-supervised learning method is adopted to optimize ROIs defined using prior knowledge with a constraint of local and global functional consistency, yielding subject specific ROIs with enhanced functional connectivity. Experiments using simulated fMRI data have demonstrated that functional consistent ROIs can be identified effectively from data with different signal to noise ratios (SNRs). Experiments using resting state fMRI data of 25 normal subjects for identifying ROIs of the default mode network have demonstrated that the proposed method is capable of identifying subject specific ROIs with stronger functional connectivity and higher consistency across subjects than existing alternative techniques, indicating that the proposed method can better identify brain network ROIs with intrinsic functional connectivity.

  19. Functionally Enigmatic Genes: A Case Study of the Brain Ignorome

    PubMed Central

    Pandey, Ashutosh K.; Lu, Lu; Wang, Xusheng; Homayouni, Ramin; Williams, Robert W.

    2014-01-01

    What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed—the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum—a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases—ELMOD1, TMEM88B, and DZANK1—we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes. PMID:24523945

  20. Estimating brain's functional graph from the structural graph's Laplacian

    NASA Astrophysics Data System (ADS)

    Abdelnour, F.; Dayan, M.; Devinsky, O.; Thesen, T.; Raj, A.

    2015-09-01

    The interplay between the brain's function and structure has been of immense interest to the neuroscience and connectomics communities. In this work we develop a simple linear model relating the structural network and the functional network. We propose that the two networks are related by the structural network's Laplacian up to a shift. The model is simple to implement and gives accurate prediction of function's eigenvalues at the subject level and its eigenvectors at group level.

  1. The microbiota-gut-brain axis in functional gastrointestinal disorders.

    PubMed

    De Palma, Giada; Collins, Stephen M; Bercik, Premysl

    2014-01-01

    Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients' quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other's expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis. PMID:24921926

  2. The microbiota-gut-brain axis in functional gastrointestinal disorders

    PubMed Central

    De Palma, Giada; Collins, Stephen M; Bercik, Premysl

    2014-01-01

    Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients’ quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other’s expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis. PMID:24921926

  3. Peptide aptamers: specific inhibitors of protein function.

    PubMed

    Hoppe-Seyler, Felix; Crnkovic-Mertens, Irena; Tomai, Evangelia; Butz, Karin

    2004-08-01

    In recent years, peptide aptamers have emerged as novel molecular tools that are useful for both basic and applied aspects of molecular medicine. Due to their ability to specifically bind to and inactivate a given target protein at the intracellular level, they provide a new experimental strategy for functional protein analyses, both in vitro and in vivo. In addition, by using peptide aptamers as "pertubagens", they can be employed for genetic analyses, in order to identify biochemical pathways, and their components, that are associated with the induction of distinct cellular phenotypes. Furthermore, peptide aptamers may be developed into diagnostic tools for the detection of a given target protein or for the generation of high-throughput protein arrays. Finally, the peptide aptamer technology has direct therapeutic implications. Peptide aptamers can be used in order to validate therapeutic targets at the intracellular level. Moreover, the peptide aptamer molecules themselves should possess therapeutic potential, both as lead structures for drug design and as a basis for the development of protein drugs. PMID:15267224

  4. Allelic Specificity of Ube3a Expression in the Mouse Brain during Postnatal Development

    PubMed Central

    JUDSON, MATTHEW C.; SOSA-PAGAN, JASON O.; DEL CID, WILMER A.; HAN, JI EUN; PHILPOT, BENJAMIN D.

    2014-01-01

    Genetic alterations of the maternal UBE3A allele result in Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, lack of speech, and difficulty with movement and balance. The combined effects of maternal UBE3A mutation and cell type-specific epigenetic silencing of paternal UBE3A are hypothesized to result in a complete loss of functional UBE3A protein in neurons. However, the allelic specificity of UBE3A expression in neurons and other cell types in the brain has yet to be characterized throughout development, including the early postnatal period when AS phenotypes emerge. Here we define maternal and paternal allele-specific Ube3a protein expression throughout postnatal brain development in the mouse, a species which exhibits orthologous epigenetic silencing of paternal Ube3a in neurons and AS-like behavioral phenotypes subsequent to maternal Ube3a deletion. We find that neurons downregulate paternal Ube3a protein expression as they mature and, with the exception of neurons born from postnatal stem cell niches, do not express detectable paternal Ube3a beyond the first postnatal week. By contrast, neurons express maternal Ube3a throughout postnatal development, during which time localization of the protein becomes increasingly nuclear. Unlike neurons, astrocytes and oligodendrotyes biallelically express Ube3a. Notably, mature oligodendrocytes emerge as the predominant Ube3a-expressing glial cell type in the cortex and white matter tracts during postnatal development. These findings demonstrate the spatiotemporal characteristics of allele-specific Ube3a expression in key brain cell types, thereby improving our understanding of the developmental parameters of paternal Ube3a silencing and the cellular basis of AS. PMID:24254964

  5. Task-specific brain reorganization in motor recovery induced by a hybrid-rehabilitation combining training with brain stimulation after stroke.

    PubMed

    Koganemaru, Satoko; Sawamoto, Nobukatsu; Aso, Toshihiko; Sagara, Akiko; Ikkaku, Tomoko; Shimada, Kenji; Kanematsu, Madoka; Takahashi, Ryosuke; Domen, Kazuhisa; Fukuyama, Hidenao; Mima, Tatsuya

    2015-03-01

    Recently, we have developed a new hybrid-rehabilitation combining 5Hz repetitive transcranial magnetic stimulation and extensor motor training of the paretic upper-limb for stroke patients with flexor hypertonia. We previously showed that the extensor-specific plastic change in M1 was associated with beneficial effects of our protocol (Koganemaru et al., 2010). Here, we investigated whether extensor-specific multiregional brain reorganization occurred after the hybrid-rehabilitation using functional magnetic resonance imaging. Eleven chronic stroke patients were scanned while performing upper-limb extensor movements. Untrained flexor movements were used as a control condition. The scanning and clinical assessments were done before, immediately and 2 weeks after the hybrid-rehabilitation. As a result, during the trained extensor movements, the imaging analysis showed a significant reduction of brain activity in the ipsilesional sensorimotor cortex, the contralesional cingulate motor cortex and the contralesional premotor cortex in association with functional improvements of the paretic hands. The activation change was not found for the control condition. Our results suggested that use-dependent plasticity induced by repetitive motor training with brain stimulation might be related to task-specific multi-regional brain reorganization. It provides a key to understand why repetitive training of the target action is one of the most powerful rehabilitation strategies to help patients. PMID:25450315

  6. Functional Reorganizations of Brain Network in Prelingually Deaf Adolescents

    PubMed Central

    Li, Wenjing; Li, Jianhong; Wang, Jieqiong; Zhou, Peng; Wang, Zhenchang; Xian, Junfang; He, Huiguang

    2016-01-01

    Previous neuroimaging studies suggested structural or functional brain reorganizations occurred in prelingually deaf subjects. However, little is known about the reorganizations of brain network architectures in prelingually deaf adolescents. The present study aims to investigate alterations of whole-brain functional network using resting-state fMRI and graph theory analysis. We recruited 16 prelingually deaf adolescents (10~18 years) and 16 normal controls matched in age and gender. Brain networks were constructed from mean time courses of 90 regions. Widely distributed network was observed in deaf subjects, with increased connectivity between the limbic system and regions involved in visual and language processing, suggesting reinforcement of the processing for the visual and verbal information in deaf adolescents. Decreased connectivity was detected between the visual regions and language regions possibly due to inferior reading or speaking skills in deaf subjects. Using graph theory analysis, we demonstrated small-worldness property did not change in prelingually deaf adolescents relative to normal controls. However, compared with healthy adolescents, eight regions involved in visual, language, and auditory processing were identified as hubs only present in prelingually deaf adolescents. These findings revealed reorganization of brain functional networks occurred in prelingually deaf adolescents to adapt to deficient auditory input. PMID:26819781

  7. Interactions between occlusion and human brain function activities.

    PubMed

    Ohkubo, C; Morokuma, M; Yoneyama, Y; Matsuda, R; Lee, J S

    2013-02-01

    There are few review articles in the area of human research that focus on the interactions between occlusion and brain function. This systematic review discusses the effect of occlusion on the health of the entire body with a focus on brain function. Available relevant articles in English from 1999 to 2011 were assessed in an online database and as hard copies in libraries. The selected 19 articles were classified into the following five categories: chewing and tongue movements, clenching and grinding, occlusal splints and occlusal interference, prosthetic rehabilitation, and pain and stimulation. The relationships between the brain activity observed in the motor and sensory cortices and movements of the oral and maxillofacial area, such as those produced by gum chewing, tapping and clenching, were investigated. It was found that the sensorimotor cortex was also affected by the placement of the occlusal interference devices, splints and implant prostheses. Brain activity may change depending on the strength of the movements in the oral and maxillofacial area. Therefore, mastication and other movements stimulate the activity in the cerebral cortex and may be helpful in preventing degradation of a brain function. However, these findings must be verified by evidence gathered from more subjects. PMID:22624951

  8. Functional Reorganizations of Brain Network in Prelingually Deaf Adolescents.

    PubMed

    Li, Wenjing; Li, Jianhong; Wang, Jieqiong; Zhou, Peng; Wang, Zhenchang; Xian, Junfang; He, Huiguang

    2016-01-01

    Previous neuroimaging studies suggested structural or functional brain reorganizations occurred in prelingually deaf subjects. However, little is known about the reorganizations of brain network architectures in prelingually deaf adolescents. The present study aims to investigate alterations of whole-brain functional network using resting-state fMRI and graph theory analysis. We recruited 16 prelingually deaf adolescents (10~18 years) and 16 normal controls matched in age and gender. Brain networks were constructed from mean time courses of 90 regions. Widely distributed network was observed in deaf subjects, with increased connectivity between the limbic system and regions involved in visual and language processing, suggesting reinforcement of the processing for the visual and verbal information in deaf adolescents. Decreased connectivity was detected between the visual regions and language regions possibly due to inferior reading or speaking skills in deaf subjects. Using graph theory analysis, we demonstrated small-worldness property did not change in prelingually deaf adolescents relative to normal controls. However, compared with healthy adolescents, eight regions involved in visual, language, and auditory processing were identified as hubs only present in prelingually deaf adolescents. These findings revealed reorganization of brain functional networks occurred in prelingually deaf adolescents to adapt to deficient auditory input. PMID:26819781

  9. Cultured pericytes from human brain show phenotypic and functional differences associated with differential CD90 expression.

    PubMed

    Park, Thomas I-H; Feisst, Vaughan; Brooks, Anna E S; Rustenhoven, Justin; Monzo, Hector J; Feng, Sheryl X; Mee, Edward W; Bergin, Peter S; Oldfield, Robyn; Graham, E Scott; Curtis, Maurice A; Faull, Richard L M; Dunbar, P Rod; Dragunow, Mike

    2016-01-01

    The human brain is a highly vascular organ in which the blood-brain barrier (BBB) tightly regulates molecules entering the brain. Pericytes are an integral cell type of the BBB, regulating vascular integrity, neuroinflammation, angiogenesis and wound repair. Despite their importance, identifying pericytes amongst other perivascular cell types and deciphering their specific role in the neurovasculature remains a challenge. Using primary adult human brain cultures and fluorescent-activated cell sorting, we identified two CD73(+)CD45(-) mesenchymal populations that showed either high or low CD90 expression. CD90 is known to be present on neurons in the brain and peripheral blood vessels. We found in the human brain, that CD90 immunostaining localised to the neurovasculature and often associated with pericytes. In vitro, CD90(+) cells exhibited higher basal proliferation, lower expression of markers αSMA and CD140b, produced less extracellular matrix (ECM) proteins, and exhibited lesser pro-inflammatory responses when compared to the CD90(-) population. Thus, CD90 distinguishes two interrelated, yet functionally distinct pericyte populations in the adult human brain that may have discrete roles in neurovascular function, immune response and scar formation. PMID:27215737

  10. Effects of Soccer Heading on Brain Structure and Function.

    PubMed

    Rodrigues, Ana Carolina; Lasmar, Rodrigo Pace; Caramelli, Paulo

    2016-01-01

    Soccer is the most popular sport in the world, with more than 265 million players worldwide, including professional and amateur ones. Soccer is unique in comparison to other sports, as it is the only sport in which participants purposely use their head to hit the ball. Heading is considered as an offensive or defensive move whereby the player's unprotected head is used to deliberately impact the ball and direct it during play. A soccer player can be subjected to an average of 6-12 incidents of heading the ball per competitive game, where the ball reaches high velocities. Moreover, in practice sessions, heading training, which involves heading the ball repeatedly at low velocities, is common. Although the scientific community, as well as the media, has focused on the effects of concussions in contact sports, the role of subconcussive impacts, as it can occur during heading, has recently gained attention, considering that it may represent an additional mechanism of cumulative brain injury. The purpose of this study is to review the existing literature regarding the effects of soccer heading on brain structure and function. Only in the last years, some investigations have addressed the impact of heading on brain structure, by using neuroimaging techniques. Similarly, there have been some recent studies investigating biochemical markers of brain injury in soccer players. There is evidence of association between heading and abnormal brain structure, but the data are still preliminary. Also, some studies have suggested that subconcussive head impacts, as heading, could cause cognitive impairment, whereas others have not corroborated this finding. Questions persist as to whether or not heading is deleterious to cognitive functioning. Further studies, especially with longitudinal designs, are needed to clarify the clinical significance of heading as a cause of brain injury and to identify risk factors. Such investigations might contribute to the establishment of safety guidelines that could help to minimize the risk of possible adverse effects of soccer on brain structure and function. PMID:27047444

  11. Effects of Soccer Heading on Brain Structure and Function

    PubMed Central

    Rodrigues, Ana Carolina; Lasmar, Rodrigo Pace; Caramelli, Paulo

    2016-01-01

    Soccer is the most popular sport in the world, with more than 265 million players worldwide, including professional and amateur ones. Soccer is unique in comparison to other sports, as it is the only sport in which participants purposely use their head to hit the ball. Heading is considered as an offensive or defensive move whereby the player’s unprotected head is used to deliberately impact the ball and direct it during play. A soccer player can be subjected to an average of 6–12 incidents of heading the ball per competitive game, where the ball reaches high velocities. Moreover, in practice sessions, heading training, which involves heading the ball repeatedly at low velocities, is common. Although the scientific community, as well as the media, has focused on the effects of concussions in contact sports, the role of subconcussive impacts, as it can occur during heading, has recently gained attention, considering that it may represent an additional mechanism of cumulative brain injury. The purpose of this study is to review the existing literature regarding the effects of soccer heading on brain structure and function. Only in the last years, some investigations have addressed the impact of heading on brain structure, by using neuroimaging techniques. Similarly, there have been some recent studies investigating biochemical markers of brain injury in soccer players. There is evidence of association between heading and abnormal brain structure, but the data are still preliminary. Also, some studies have suggested that subconcussive head impacts, as heading, could cause cognitive impairment, whereas others have not corroborated this finding. Questions persist as to whether or not heading is deleterious to cognitive functioning. Further studies, especially with longitudinal designs, are needed to clarify the clinical significance of heading as a cause of brain injury and to identify risk factors. Such investigations might contribute to the establishment of safety guidelines that could help to minimize the risk of possible adverse effects of soccer on brain structure and function. PMID:27047444

  12. Insights into brain function and neural plasticity using magnetic source imaging.

    PubMed

    Simos, P G; Papanicolaou, A C; Breier, J I; Fletcher, J M; Wheless, J W; Maggio, W W; Gormley, W; Constantinou, J E; Kramer, L

    2000-03-01

    This review outlines the rationale for the use of magnetoencephalography (MEG) or magnetic source imaging (MSI), a noninvasive functional imaging technique, and the features that any imaging method should display to make a substantial contribution to cognitive neuroscience. After a brief discussion of the basic experimental approach used in the authors' studies, the use of early sensory components of brain magnetic responses is reviewed to address issues of the functional organization of the primary sensory cortices, followed by a comment on the clinical use of these components. Second, normative studies focusing on the late components of magnetic responses for establishing the validity and reliability of MSI maps of the language-specific cortex in normal subjects are reviewed. Third, the authors' investigations of fine spatiotemporal features of brain activation maps, specific to receptive language and to reading, are reviewed. Fourth, experience with presurgical mapping of the language-specific cortex in neurosurgery candidates and in patients undergoing the "Wada" procedure is summarized followed by a comment on the perfect agreement of the MSI maps with those derived by more direct invasive brain mapping procedures. Fifth. MSI-derived evidence of often dramatic, functional reorganization of brain areas subserving both simple sensory and linguistic functions is summarized along with comments on the use of MSI as a means for investigating brain plasticity. Finally, in the sixth section of this review, the authors relate their experience with the use of MSI in deriving brain activation profiles during silent reading of real words and pseudowords that are specific to dyslexic children. The review concludes with a discussion on the further use of MSI in assessing, among other issues, the effectiveness of intervention strategies designed to improve reading fluency in dyslexic children. PMID:10831106

  13. Functional constraints in the evolution of brain circuits

    PubMed Central

    Bosman, Conrado A.; Aboitiz, Francisco

    2015-01-01

    Regardless of major anatomical and neurodevelopmental differences, the vertebrate isocortex shows a remarkably well-conserved organization. In the isocortex, reciprocal connections between excitatory and inhibitory neurons are distributed across multiple layers, encompassing modular, dynamical and recurrent functional networks during information processing. These dynamical brain networks are often organized in neuronal assemblies interacting through rhythmic phase relationships. Accordingly, these oscillatory interactions are observed across multiple brain scale levels, and they are associated with several sensory, motor, and cognitive processes. Most notably, oscillatory interactions are also found in the complete spectrum of vertebrates. Yet, it is unknown why this functional organization is so well conserved in evolution. In this perspective, we propose some ideas about how functional requirements of the isocortex can account for the evolutionary stability observed in microcircuits across vertebrates. We argue that isocortex architectures represent canonical microcircuits resulting from: (i) the early selection of neuronal architectures based on the oscillatory excitatory-inhibitory balance, which lead to the implementation of compartmentalized oscillations and (ii) the subsequent emergence of inferential coding strategies (predictive coding), which are able to expand computational capacities. We also argue that these functional constraints may be the result of several advantages that oscillatory activity contributes to brain network processes, such as information transmission and code reliability. In this manner, similarities in mesoscale brain circuitry and input-output organization between different vertebrate groups may reflect evolutionary constraints imposed by these functional requirements, which may or may not be traceable to a common ancestor. PMID:26388716

  14. Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

    NASA Astrophysics Data System (ADS)

    Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

    1998-12-01

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

  15. Brain tissue segmentation of neonatal MR images using a longitudinal subject-specific probabilistic atlas

    NASA Astrophysics Data System (ADS)

    Shi, Feng; Fan, Yong; Tang, Songyuan; Gilmore, John; Lin, Weili; Shen, Dinggang

    2009-02-01

    Brain tissue segmentation of neonate MR images is a challenging task in study of early brain development, due to low signal contrast among brain tissues and high intensity variability especially in white matter. Among various brain tissue segmentation algorithms, the atlas-based segmentation techniques can potentially produce reasonable segmentation results on neonatal brain images. However, their performance on the population-based atlas is still limited due to the high variability of brain structures across different individuals. Moreover, it may be impossible to generate a reasonable probabilistic atlas for neonates without tissue segmentation samples. To overcome these limitations, we present a neonatal brain tissue segmentation method by taking advantage of the longitudinal data available in our study to establish a subject-specific probabilistic atlas. In particular, tissue segmentation of the neonatal brain is formulated as two iterative steps of bias correction and probabilistic atlas based tissue segmentation, along with the guidance of brain tissue segmentation resulted from the later time images of the same subject which serve as a subject-specific probabilistic atlas. The proposed method has been evaluated qualitatively through visual inspection and quantitatively by comparing with manual delineation results. Experimental results show that the utilization of a subject-specific probabilistic atlas can substantially improve tissue segmentation of neonatal brain images.

  16. Fluctuations in Neuronal Activity: Clues to Brain Function

    NASA Astrophysics Data System (ADS)

    Pérez Velazquez, José L.; Guevara, Ramón; Belkas, Jason; Wennberg, Richard; Senjanoviè, Goran; García Dominguez, Luis

    2005-08-01

    Recordings from neuronal preparations, either in vitro or in the intact brain, are characterized by fluctuations, what is commonly considered as "noise". Due to the current recording and analysis methods, it is not feasible to separate what we term noise, from the "meaningful" neuronal activity. We propose that fluctuations serve to maintain brain activity in an optimal state for cognitive processing, not allowing it to fall into long-term periodic behaviour. We have studied fluctuations in magnetoencephalographic (MEG) recordings from normal subjects and epileptic patients, in electroencephalographic (EEG) recordings from children with impact injury, as well as in intracerebral electrophysiological recordings in freely moving rats. Specifically, we have determined phase locking patterns between brain areas from these recordings, which display fluctuations at different scales. We submit the idea that the variability in phase synchronization affords a more complete search of all possible phase differences in a hypothetical phase-locking state space that contributes to brain information processing. In brain pathologies, like epileptiform activity here studied, different levels of fluctuations in phase synchrony may favour the generation of stable synchronized states that characterize epileptic seizures. While the border between noise and high-dimensional dynamics is fuzzy, the scrutiny of neuronal fluctuations at different levels will provide important insights to the unravelling of the relation between brain and behaviour.

  17. Rationally Designed MicroRNA-Based Genetic Classifiers Target Specific Neurons in the Brain

    PubMed Central

    Cha, Susie S.; Goodloe, Michael; Wong, Wilson W.; Han, Xue

    2015-01-01

    Targeting transgene expression to specific cell types in vivo has proven instrumental in characterizing the functional role of defined cell populations. Genetic classifiers, synthetic transgene constructs designed to restrict expression to particular classes of cells, commonly rely on transcriptional promoters to define cellular specificity. However, the large size of many natural promoters complicates their use in viral vectors, an important mode of transgene delivery in the brain and in human gene therapy. Here, we expanded upon an emerging classifier platform, orthogonal to promoter-based strategies, that exploits endogenous microRNA regulation to target gene expression. Such classifiers have been extensively explored in other tissues; however, their use in the nervous system has thus far been limited to targeting gene expression between neurons and supporting cells. Here, we tested the possibility of using combinatory microRNA regulation to specify gene targeting between neuronal subtypes, and successfully targeted inhibitory cells in the neocortex. These classifiers demonstrate the feasibility of designing a new generation of microRNA-based neuron-type- and brain-region-specific gene expression targeting neurotechnologies. PMID:25848814

  18. Brain tumour cells interconnect to a functional and resistant network.

    PubMed

    Osswald, Matthias; Jung, Erik; Sahm, Felix; Solecki, Gergely; Venkataramani, Varun; Blaes, Jonas; Weil, Sophie; Horstmann, Heinz; Wiestler, Benedikt; Syed, Mustafa; Huang, Lulu; Ratliff, Miriam; Karimian Jazi, Kianush; Kurz, Felix T; Schmenger, Torsten; Lemke, Dieter; Gömmel, Miriam; Pauli, Martin; Liao, Yunxiang; Häring, Peter; Pusch, Stefan; Herl, Verena; Steinhäuser, Christian; Krunic, Damir; Jarahian, Mostafa; Miletic, Hrvoje; Berghoff, Anna S; Griesbeck, Oliver; Kalamakis, Georgios; Garaschuk, Olga; Preusser, Matthias; Weiss, Samuel; Liu, Haikun; Heiland, Sabine; Platten, Michael; Huber, Peter E; Kuner, Thomas; von Deimling, Andreas; Wick, Wolfgang; Winkler, Frank

    2015-12-01

    Astrocytic brain tumours, including glioblastomas, are incurable neoplasms characterized by diffusely infiltrative growth. Here we show that many tumour cells in astrocytomas extend ultra-long membrane protrusions, and use these distinct tumour microtubes as routes for brain invasion, proliferation, and to interconnect over long distances. The resulting network allows multicellular communication through microtube-associated gap junctions. When damage to the network occurred, tumour microtubes were used for repair. Moreover, the microtube-connected astrocytoma cells, but not those remaining unconnected throughout tumour progression, were protected from cell death inflicted by radiotherapy. The neuronal growth-associated protein 43 was important for microtube formation and function, and drove microtube-dependent tumour cell invasion, proliferation, interconnection, and radioresistance. Oligodendroglial brain tumours were deficient in this mechanism. In summary, astrocytomas can develop functional multicellular network structures. Disconnection of astrocytoma cells by targeting their tumour microtubes emerges as a new principle to reduce the treatment resistance of this disease. PMID:26536111

  19. Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.

    PubMed

    Mahncke, Henry W; Bronstone, Amy; Merzenich, Michael M

    2006-01-01

    Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults. PMID:17046669

  20. Improved measurement of drug exposure in the brain using drug-specific correction for residual blood

    PubMed Central

    Fridén, Markus; Ljungqvist, Helena; Middleton, Brian; Bredberg, Ulf; Hammarlund-Udenaes, Margareta

    2010-01-01

    A major challenge associated with the determination of the unbound brain-to-plasma concentration ratio of a drug (Kp,uu,brain), is the error associated with correction for the drug in various vascular spaces of the brain, i.e., in residual blood. The apparent brain vascular spaces of plasma water (Vwater, 10.3 μL/g brain), plasma proteins (Vprotein, 7.99 μL/g brain), and the volume of erythrocytes (Ver, 2.13 μL/g brain) were determined and incorporated into a novel, drug-specific correction model that took the drug-unbound fraction in the plasma (fu,p) into account. The correction model was successfully applied for the determination of Kp,uu,brain for indomethacin, loperamide, and moxalactam, which had potential problems associated with correction. The influence on correction of the drug associated with erythrocytes was shown to be minimal. Therefore, it is proposed that correction for residual blood can be performed using an effective plasma space in the brain (Veff), which is calculated from the measured fu,p of the particular drug as well as from the estimates of Vwater and Vprotein, which are provided in this study. Furthermore, the results highlight the value of determining Kp,uu,brain with statistical precision to enable appropriate interpretation of brain exposure for drugs that appear to be restricted to the brain vascular spaces. PMID:19756019

  1. Brain-Specific Superoxide Dismutase 2 Deficiency Causes Perinatal Death with Spongiform Encephalopathy in Mice

    PubMed Central

    Izuo, Naotaka; Nojiri, Hidetoshi; Uchiyama, Satoshi; Noda, Yoshihiro; Kawakami, Satoru; Kojima, Shuji; Sasaki, Toru; Shirasawa, Takuji; Shimizu, Takahiko

    2015-01-01

    Oxidative stress is believed to greatly contribute to the pathogenesis of various diseases, including neurodegeneration. Impairment of mitochondrial energy production and increased mitochondrial oxidative damage are considered early pathological events that lead to neurodegeneration. Manganese superoxide dismutase (Mn-SOD, SOD2) is a mitochondrial antioxidant enzyme that converts toxic superoxide to hydrogen peroxide. To investigate the pathological role of mitochondrial oxidative stress in the central nervous system, we generated brain-specific SOD2-deficient mice (B-Sod2−/−) using nestin-Cre-loxp system. B-Sod2−/− showed perinatal death, along with severe growth retardation. Interestingly, these mice exhibited spongiform neurodegeneration in motor cortex, hippocampus, and brainstem, accompanied by gliosis. In addition, the mutant mice had markedly decreased mitochondrial complex II activity, but not complex I or IV, in the brain based on enzyme histochemistry. Furthermore, brain lipid peroxidation was significantly increased in the B-Sod2−/−, without any compensatory alterations of the activities of other antioxidative enzymes, such as catalase or glutathione peroxidase. These results suggest that SOD2 protects the neural system from oxidative stress in the perinatal stage and is essential for infant survival and central neural function in mice. PMID:26301039

  2. Sharing self-related information is associated with intrinsic functional connectivity of cortical midline brain regions.

    PubMed

    Meshi, Dar; Mamerow, Loreen; Kirilina, Evgeniya; Morawetz, Carmen; Margulies, Daniel S; Heekeren, Hauke R

    2016-01-01

    Human beings are social animals and they vary in the degree to which they share information about themselves with others. Although brain networks involved in self-related cognition have been identified, especially via the use of resting-state experiments, the neural circuitry underlying individual differences in the sharing of self-related information is currently unknown. Therefore, we investigated the intrinsic functional organization of the brain with respect to participants' degree of self-related information sharing using resting state functional magnetic resonance imaging and self-reported social media use. We conducted seed-based correlation analyses in cortical midline regions previously shown in meta-analyses to be involved in self-referential cognition: the medial prefrontal cortex (MPFC), central precuneus (CP), and caudal anterior cingulate cortex (CACC). We examined whether and how functional connectivity between these regions and the rest of the brain was associated with participants' degree of self-related information sharing. Analyses revealed associations between the MPFC and right dorsolateral prefrontal cortex (DLPFC), as well as the CP with the right DLPFC, the left lateral orbitofrontal cortex and left anterior temporal pole. These findings extend our present knowledge of functional brain connectivity, specifically demonstrating how the brain's intrinsic functional organization relates to individual differences in the sharing of self-related information. PMID:26948055

  3. Pro-cognitive drug effects modulate functional brain network organization

    PubMed Central

    Giessing, Carsten; Thiel, Christiane M.

    2012-01-01

    Previous studies document that cholinergic and noradrenergic drugs improve attention, memory and cognitive control in healthy subjects and patients with neuropsychiatric disorders. In humans neural mechanisms of cholinergic and noradrenergic modulation have mainly been analyzed by investigating drug-induced changes of task-related neural activity measured with functional magnetic resonance imaging (fMRI). Endogenous neural activity has often been neglected. Further, although drugs affect the coupling between neurons, only a few human studies have explicitly addressed how drugs modulate the functional connectome, i.e., the functional neural interactions within the brain. These studies have mainly focused on synchronization or correlation of brain activations. Recently, there are some drug studies using graph theory and other new mathematical approaches to model the brain as a complex network of interconnected processing nodes. Using such measures it is possible to detect not only focal, but also subtle, widely distributed drug effects on functional network topology. Most important, graph theoretical measures also quantify whether drug-induced changes in topology or network organization facilitate or hinder information processing. Several studies could show that functional brain integration is highly correlated with behavioral performance suggesting that cholinergic and noradrenergic drugs which improve measures of cognitive performance should increase functional network integration. The purpose of this paper is to show that graph theory provides a mathematical tool to develop theory-driven biomarkers of pro-cognitive drug effects, and also to discuss how these approaches can contribute to the understanding of the role of cholinergic and noradrenergic modulation in the human brain. Finally we discuss the “global workspace” theory as a theoretical framework of pro-cognitive drug effects and argue that pro-cognitive effects of cholinergic and noradrenergic drugs might be related to higher network integration. PMID:22973209

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

    PubMed

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

    2016-05-01

    Sudden sensorineural hearing loss (SSNHL) is generally defined as sensorineural hearing loss of 30 dB or greater over at least three contiguous audiometric frequencies and within a three-day period. This hearing loss is usually unilateral and can be associated with tinnitus and vertigo. The pathogenesis of unilateral sudden sensorineural hearing loss is still unknown, and the alterations in the functional connectivity are suspected to involve one possible pathogenesis. Despite scarce findings with respect to alterations in brain functional networks in unilateral sudden sensorineural hearing loss, the alterations of the whole brain functional connectome and whether these alterations were already in existence in the acute period remains unknown. The aim of this study was to investigate the alterations of brain functional connectome in two large samples of unilateral sudden sensorineural hearing loss patients and to investigate the correlation between unilateral sudden sensorineural hearing loss characteristics and changes in the functional network properties. Pure tone audiometry was performed to assess hearing ability. Abnormal changes in the peripheral auditory system were examined using conventional magnetic resonance imaging. The graph theoretical network analysis method was used to detect brain connectome alterations in unilateral sudden sensorineural hearing loss. Compared with the control groups, both groups of unilateral SSNHL patients exhibited a significantly increased clustering coefficient, global efficiency, and local efficiency but a significantly decreased characteristic path length. In addition, the primary increased nodal strength (e.g., nodal betweenness, hubs) was observed in several regions primarily, including the limbic and paralimbic systems, and in the auditory network brain areas. These findings suggest that the alteration of network organization already exists in unilateral sudden sensorineural hearing loss patients within the acute period and that the functional connectome of unilateral SSNHL patients is characterized by a shift toward small-worldization. Additionally, we hope that these findings will help to elucidate unilateral SSNHL through a new research perspective and provide insight for the potential pathophysiology of unilateral SSNHL. PMID:26969260

  5. Predictors of physical functioning in postoperative brain tumor patients.

    PubMed

    Tankumpuan, Thitipong; Utriyaprasit, Ketsarin; Chayaput, Prangtip; Itthimathin, Parunut

    2015-02-01

    A cross-sectional predictive design was used to study the relationships among recovery symptoms, mood state, and physical functioning and to identify predictors of physical functioning in patients who underwent surgery for brain tumor at the first follow-up visit (2 weeks) after hospital discharge. The sample included 88 patients who were 18 years or older, had full level of consciousness, and underwent first-time surgery for brain tumor without other adjuvant treatments from a tertiary hospital in Bangkok, Thailand. Descriptive statistics, Pearson product-moment correlation coefficient, and multiple regression were used for data analysis. The results revealed that most participants were women (75%) with an average age of 45.18 ± 11.49 years, having benign brain tumors (91%) and pathological results as meningioma (48.9%). The most common recovery symptoms were pain (mean = 3.2, SD = 2.6) and sleep disturbance (mean = 3.1, SD = 3.0). As for mood state, the problem of confusion was found the most (mean = 4.6, SD = 2.7). The physical functioning problem found the most was work aspect (mean = 66.3, SD = 13.3). Recovery symptoms had positive relationships with physical functioning and mood state (r = .406, .716; p < .01), respectively. At the same time, mood state had positive relationships with physical functioning (r = .288, p < .01). Recovery symptoms, total mood disturbance, fatigue, and vigor were statistically significant predictors of physical functioning and could explain variance of postoperative physical functioning in these patients at 2 weeks after discharge by 35%. Total mood disturbance was the strongest predictor of physical functioning followed by vigor, fatigue, and recovery symptom, respectively. Interventions to improve physical functioning in postoperative brain tumor patients during home recovery should account for not only recovery symptom management but also mood state. PMID:25565598

  6. Modulatory Interactions of Resting-State Brain Functional Connectivity

    PubMed Central

    Di, Xin; Biswal, Bharat B.

    2013-01-01

    The functional brain connectivity studies are generally based on the synchronization of the resting-state functional magnetic resonance imaging (fMRI) signals. Functional connectivity measures usually assume a stable relationship over time; however, accumulating studies have reported time-varying properties of strength and spatial distribution of functional connectivity. The present study explored the modulation of functional connectivity between two regions by a third region using the physiophysiological interaction (PPI) technique. We first identified eight brain networks and two regions of interest (ROIs) representing each of the networks using a spatial independent component analysis. A voxel-wise analysis was conducted to identify regions that showed modulatory interactions (PPI) with the two ROIs of each network. Mostly, positive modulatory interactions were observed within regions involved in the same system. For example, the two regions of the dorsal attention network revealed modulatory interactions with the regions related to attention, while the two regions of the extrastriate network revealed modulatory interactions with the regions in the visual cortex. In contrast, the two regions of the default mode network (DMN) revealed negative modulatory interactions with the regions in the executive network, and vice versa, suggesting that the activities of one network may be associated with smaller within network connectivity of the competing network. These results validate the use of PPI analysis to study modulation of resting-state functional connectivity by a third region. The modulatory effects may provide a better understanding of complex brain functions. PMID:24023609

  7. "Hotheaded": the role OF TRPV1 in brain functions.

    PubMed

    Martins, D; Tavares, I; Morgado, C

    2014-10-01

    The TRPV1 (vanilloid 1) channel is best known for its role in sensory transmission in the nociceptive neurons of the peripheral nervous system. Although first studied in the dorsal root ganglia as the receptor for capsaicin, TRPV1 has been recently recognized to have a broader distribution in the central nervous system, where it is likely to constitute an atypical neurotransmission system involved in several functions through modulation of both neuronal and glial activities. The endovanilloid-activated brain TRPV1 channels seem to be involved in somatosensory, motor and visceral functions. Recent studies suggested that TRPV1 channels also account for more complex functions, as addiction, anxiety, mood and cognition/learning. However, more studies are needed before the relevance of TRPV1 in brain activity can be clearly stated. This review highlights the increasing importance of TRPV1 as a regulator of brain function and discusses possible bases for the future development of new therapeutic approaches that by targeting brain TRPV1 receptors might be used for the treatment of several neurological disorders. PMID:24887171

  8. Functional craniology and brain evolution: from paleontology to biomedicine

    PubMed Central

    Bruner, Emiliano; de la Cuétara, José Manuel; Masters, Michael; Amano, Hideki; Ogihara, Naomichi

    2014-01-01

    Anatomical systems are organized through a network of structural and functional relationships among their elements. This network of relationships is the result of evolution, it represents the actual target of selection, and it generates the set of rules orienting and constraining the morphogenetic processes. Understanding the relationship among cranial and cerebral components is necessary to investigate the factors that have influenced and characterized our neuroanatomy, and possible drawbacks associated with the evolution of large brains. The study of the spatial relationships between skull and brain in the human genus has direct relevance in cranial surgery. Geometrical modeling can provide functional perspectives in evolution and brain physiology, like in simulations to investigate metabolic heat production and dissipation in the endocranial form. Analysis of the evolutionary constraints between facial and neural blocks can provide new information on visual impairment. The study of brain form variation in fossil humans can supply a different perspective for interpreting the processes behind neurodegeneration and Alzheimer’s disease. Following these examples, it is apparent that paleontology and biomedicine can exchange relevant information and contribute at the same time to the development of robust evolutionary hypotheses on brain evolution, while offering more comprehensive biological perspectives with regard to the interpretation of pathological processes. PMID:24765064

  9. Function of insulin in snail brain in associative learning.

    PubMed

    Kojima, S; Sunada, H; Mita, K; Sakakibara, M; Lukowiak, K; Ito, E

    2015-10-01

    Insulin is well known as a hormone regulating glucose homeostasis across phyla. Although there are insulin-independent mechanisms for glucose uptake in the mammalian brain, which had contributed to a perception of the brain as an insulin-insensitive organ for decades, the finding of insulin and its receptors in the brain revolutionized the concept of insulin signaling in the brain. However, insulin's role in brain functions, such as cognition, attention, and memory, remains unknown. Studies using invertebrates with their open blood-vascular system have the promise of promoting a better understanding of the role played by insulin in mediating/modulating cognitive functions. In this review, the relationship between insulin and its impact on long-term memory (LTM) is discussed particularly in snails. The pond snail Lymnaea stagnalis has the ability to undergo conditioned taste aversion (CTA), that is, it associatively learns and forms LTM not to respond with a feeding response to a food that normally elicits a robust feeding response. We show that molluscan insulin-related peptides are up-regulated in snails exhibiting CTA-LTM and play a key role in the causal neural basis of CTA-LTM. We also survey the relevant literature of the roles played by insulin in learning and memory in other phyla. PMID:26233474

  10. Current Trends and Challenges in MRI Acquisitions to Investigate Brain Function

    PubMed Central

    Sutton, Bradley P.; Ouyang, Cheng; Karampinos, Dimitrios C.; Miller, Gregory A.

    2009-01-01

    Functional magnetic resonance imaging (fMRI) studies using the blood oxygenation level dependent (BOLD) response have become a widely used tool for noninvasive assessment of functional organization of the brain. Yet the technique is still fairly new, with many significant challenges remaining. Capitalizing on additional contrast mechanisms available with MRI, several other functional imaging techniques have been developed that potentially provide improved quantification or specificity of neuronal function. This article reviews the challenges and the current state of the art in MRI-based methods of imaging cognitive function. PMID:19236896

  11. The Functional Connectivity Landscape of the Human Brain

    PubMed Central

    Fatima, Zainab; Jonides, John; McIntosh, Anthony R.

    2014-01-01

    Functional brain networks emerge and dissipate over a primarily static anatomical foundation. The dynamic basis of these networks is inter-regional communication involving local and distal regions. It is assumed that inter-regional distances play a pivotal role in modulating network dynamics. Using three different neuroimaging modalities, 6 datasets were evaluated to determine whether experimental manipulations asymmetrically affect functional relationships based on the distance between brain regions in human participants. Contrary to previous assumptions, here we show that short- and long-range connections are equally likely to strengthen or weaken in response to task demands. Additionally, connections between homotopic areas are the most stable and less likely to change compared to any other type of connection. Our results point to a functional connectivity landscape characterized by fluid transitions between local specialization and global integration. This ability to mediate functional properties irrespective of spatial distance may engender a diverse repertoire of cognitive processes when faced with a dynamic environment. PMID:25350370

  12. Covert brand recognition engages emotion-specific brain networks.

    PubMed

    Casarotto, Silvia; Ricciardi, Emiliano; Romani, Simona; Dalli, Daniele; Pietrini, Pietro

    2012-12-01

    Consumer goods' brands have become a major driver of consumers' choice: they have got symbolic, relational and even social properties that add substantial cultural and affective value to goods and services. Therefore, measuring the role of brands in consumers' cognitive and affective processes would be very helpful to better understand economic decision making. This work aimed at finding the neural correlates of automatic, spontaneous emotional response to brands, showing how deeply integrated are consumption symbols within the cognitive and affective processes of individuals. Functional magnetic resonance imaging (fMRI) was measured during a visual oddball paradigm consisting in the presentation of scrambled pictures as frequent stimuli, colored squares as targets, and brands and emotional pictures (selected from the International Affective Picture System [IAPS]) as emotionally-salient distractors. Affective rating of brands was assessed individually after scanning by a validated questionnaire. Results showed that, similarly to IAPS pictures, brands activated a well-defined emotional network, including amygdala and dorsolateral prefrontal cortex, highly specific of affective valence. In conclusion, this work identified the neural correlates of brands within cognitive and affective processes of consumers. PMID:23479459

  13. Memory Function Before and After Whole Brain Radiotherapy in Patients With and Without Brain Metastases

    SciTech Connect

    Welzel, Grit Fleckenstein, Katharina; Schaefer, Joerg; Hermann, Brigitte; Kraus-Tiefenbacher, Uta; Mai, Sabine K.; Wenz, Frederik

    2008-12-01

    Purpose: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. Methods and Materials: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. Results: Before therapy, prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. Conclusions: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects.

  14. Fine-grained mapping of mouse brain functional connectivity with resting-state fMRI.

    PubMed

    Mechling, Anna E; Hübner, Neele S; Lee, Hsu-Lei; Hennig, Jürgen; von Elverfeldt, Dominik; Harsan, Laura-Adela

    2014-08-01

    Understanding the intrinsic circuit-level functional organization of the brain has benefited tremendously from the advent of resting-state fMRI (rsfMRI). In humans, resting-state functional network has been consistently mapped and its alterations have been shown to correlate with symptomatology of various neurological or psychiatric disorders. To date, deciphering the mouse brain functional connectivity (MBFC) with rsfMRI remains a largely underexplored research area, despite the plethora of human brain disorders that can be modeled in this specie. To pave the way from pre-clinical to clinical investigations we characterized here the intrinsic architecture of mouse brain functional circuitry, based on rsfMRI data acquired at 7T using the Cryoprobe technology. High-dimensional spatial group independent component analysis demonstrated fine-grained segregation of cortical and subcortical networks into functional clusters, overlapping with high specificity onto anatomical structures, down to single gray matter nuclei. These clusters, showing a high level of stability and reliability in their patterning, formed the input elements for computing the MBFC network using partial correlation and graph theory. Its topological architecture conserved the fundamental characteristics described for the human and rat brain, such as small-worldness and partitioning into functional modules. Our results additionally showed inter-modular interactions via "network hubs". Each major functional system (motor, somatosensory, limbic, visual, autonomic) was found to have representative hubs that might play an important input/output role and form a functional core for information integration. Moreover, the rostro-dorsal hippocampus formed the highest number of relevant connections with other brain areas, highlighting its importance as core structure for MBFC. PMID:24718287

  15. Topological Comparison of Brain Functional Networks and Internet Service Providers

    NASA Astrophysics Data System (ADS)

    Leibnitz, Kenji; Shimokawa, Tetsuya; Umehara, Hiroaki; Murata, Tsutomu

    Network structures can be found in almost any kind of natural or artificial systems as transport medium for communication between the respective nodes. In this paper we study certain key topological features of brain functional networks obtained from functional magnetic resonance imaging (fMRI) measurements. We compare complex network measures of the extracted topologies with those from Internet service providers (ISPs). Our goal is to identify important features which will be helpful in designing more robust and adaptive future information network architectures.

  16. Human brain somatic representation: a functional magnetic resonance mapping

    NASA Astrophysics Data System (ADS)

    Romero-Romo, Juan; Rojas, Rafael; Salgado, Perla; Sánchez-Cortázar, Julián; Vazquez-Vela, Arturo; Barrios, Fernando A.

    2001-10-01

    Central nervous system studies of injury and plasticity for the reorganization in the phantom limb sensation area presented. In particular functional magnetic resonance imaging (fMRI) mapping of the somatic and motor cortex of amputee patients, in the case of referred sensations. Using fMRI we can show the correlation between structure and functional field and study the reorganization due to plasticity in the brain.

  17. Left Brain vs. Right Brain: Findings on Visual Spatial Capacities and the Functional Neurology of Giftedness

    ERIC Educational Resources Information Center

    Kalbfleisch, M. Layne; Gillmarten, Charles

    2013-01-01

    As neuroimaging technologies increase their sensitivity to assess the function of the human brain and results from these studies draw the attention of educators, it becomes paramount to identify misconceptions about what these data illustrate and how these findings might be applied to educational contexts. Some of these "neuromyths" have

  18. Left Brain vs. Right Brain: Findings on Visual Spatial Capacities and the Functional Neurology of Giftedness

    ERIC Educational Resources Information Center

    Kalbfleisch, M. Layne; Gillmarten, Charles

    2013-01-01

    As neuroimaging technologies increase their sensitivity to assess the function of the human brain and results from these studies draw the attention of educators, it becomes paramount to identify misconceptions about what these data illustrate and how these findings might be applied to educational contexts. Some of these "neuromyths" have…

  19. Anatomical and functional assemblies of brain BOLD oscillations

    PubMed Central

    Baria, Alexis T.; Baliki, Marwan N.; Parrish, Todd; Apkarian, A. Vania

    2011-01-01

    Brain oscillatory activity has long been thought to have spatial properties, the details of which are unresolved. Here we examine spatial organizational rules for the human brain oscillatory activity as measured by blood oxygen level-dependent (BOLD). Resting state BOLD signal was transformed into frequency space (Welch’s method), averaged across subjects, and its spatial distribution studied as a function of four frequency bands, spanning the full bandwidth of BOLD. The brain showed anatomically constrained distribution of power for each frequency band. This result was replicated on a repository dataset of 195 subjects. Next, we examined larger-scale organization by parceling the neocortex into regions approximating Brodmann Areas (BAs). This indicated that BAs of simple function/connectivity (unimodal), vs. complex properties (transmodal), are dominated by low frequency BOLD oscillations, and within the visual ventral stream we observe a graded shift of power to higher frequency bands for BAs further removed from the primary visual cortex (increased complexity), linking frequency properties of BOLD to hodology. Additionally, BOLD oscillation properties for the default mode network demonstrated that it is composed of distinct frequency dependent regions. When the same analysis was performed on a visual-motor task, frequency-dependent global and voxel-wise shifts in BOLD oscillations could be detected at brain sites mostly outside those identified with general linear modeling. Thus, analysis of BOLD oscillations in full bandwidth uncovers novel brain organizational rules, linking anatomical structures and functional networks to characteristic BOLD oscillations. The approach also identifies changes in brain intrinsic properties in relation to responses to external inputs. PMID:21613505

  20. Effects of exercise on brain functions in diabetic animal models

    PubMed Central

    Yi, Sun Shin

    2015-01-01

    Human life span has dramatically increased over several decades, and the quality of life has been considered to be equally important. However, diabetes mellitus (DM) characterized by problems related to insulin secretion and recognition has become a serious health problem in recent years that threatens human health by causing decline in brain functions and finally leading to neurodegenerative diseases. Exercise is recognized as an effective therapy for DM without medication administration. Exercise studies using experimental animals are a suitable option to overcome this drawback, and animal studies have improved continuously according to the needs of the experimenters. Since brain health is the most significant factor in human life, it is very important to assess brain functions according to the different exercise conditions using experimental animal models. Generally, there are two types of DM; insulin-dependent type 1 DM and an insulin-independent type 2 DM (T2DM); however, the author will mostly discuss brain functions in T2DM animal models in this review. Additionally, many physiopathologic alterations are caused in the brain by DM such as increased adiposity, inflammation, hormonal dysregulation, uncontrolled hyperphagia, insulin and leptin resistance, and dysregulation of neurotransmitters and declined neurogenesis in the hippocampus and we describe how exercise corrects these alterations in animal models. The results of changes in the brain environment differ according to voluntary, involuntary running exercises and resistance exercise, and gender in the animal studies. These factors have been mentioned in this review, and this review will be a good reference for studying how exercise can be used with therapy for treating DM. PMID:25987956

  1. Effects of exercise on brain functions in diabetic animal models.

    PubMed

    Yi, Sun Shin

    2015-05-15

    Human life span has dramatically increased over several decades, and the quality of life has been considered to be equally important. However, diabetes mellitus (DM) characterized by problems related to insulin secretion and recognition has become a serious health problem in recent years that threatens human health by causing decline in brain functions and finally leading to neurodegenerative diseases. Exercise is recognized as an effective therapy for DM without medication administration. Exercise studies using experimental animals are a suitable option to overcome this drawback, and animal studies have improved continuously according to the needs of the experimenters. Since brain health is the most significant factor in human life, it is very important to assess brain functions according to the different exercise conditions using experimental animal models. Generally, there are two types of DM; insulin-dependent type 1 DM and an insulin-independent type 2 DM (T2DM); however, the author will mostly discuss brain functions in T2DM animal models in this review. Additionally, many physiopathologic alterations are caused in the brain by DM such as increased adiposity, inflammation, hormonal dysregulation, uncontrolled hyperphagia, insulin and leptin resistance, and dysregulation of neurotransmitters and declined neurogenesis in the hippocampus and we describe how exercise corrects these alterations in animal models. The results of changes in the brain environment differ according to voluntary, involuntary running exercises and resistance exercise, and gender in the animal studies. These factors have been mentioned in this review, and this review will be a good reference for studying how exercise can be used with therapy for treating DM. PMID:25987956

  2. Complex function in the dynamic brain. Comment on “Understanding brain networks and brain organization” by Luiz Pessoa

    NASA Astrophysics Data System (ADS)

    Anderson, Michael L.

    2014-09-01

    There is much to commend in this excellent overview of the progress we've made toward-and the challenges that remain for-developing an empirical framework for neuroscience that is adequate to the dynamic complexity of the brain [17]. Here I will limit myself first to highlighting the concept of dynamic affiliation, which I take to be the central feature of the functional architecture of the brain, and second to clarifying Pessoa's brief discussion of the ontology of cognition, to be sure readers appreciate this crucial issue.

  3. [On the question of the organization of brain function: cortical associations, «disconnection» syndrome and higher brain functions].

    PubMed

    Damulin, I V

    2015-01-01

    The review considers the structural/functional brain organization, the disturbance of which is accompanied by the development of cognitive and behavioral disorders. The significance of the disruption of parallel circuits connecting frontal lobes with subcortical structures (the basal ganglia, thalamus, cerebellum) is highlighted. This disruption is clinically described as "disconnection" syndrome. The associations between the basal ganglia and the cortex of the large cerebral hemispheres responsible for motor, cognitive and emotional/behavioral functions do not restricted to these spheres and is characteristic not only of frontal brain areas. There are circuits connecting other brain compartments and the basal ganglia that provide perception, and are involved in decision making on the basis of input information of different modalities.The improvement of understanding of the pathophysiology and neurochemistry of these structures opens new possibilities for selective action on some or other circuit to achieve the best therapeutic result. PMID:26978059

  4. Tesmilifene modifies brain endothelial functions and opens the blood-brain/blood-glioma barrier.

    PubMed

    Walter, Fruzsina R; Veszelka, Szilvia; Pásztói, Mária; Péterfi, Zoltán A; Tóth, András; Rákhely, Gábor; Cervenak, László; Ábrahám, Csongor S; Deli, Mária A

    2015-09-01

    Tesmilifene, a tamoxifen analog with antihistamine action, has chemopotentiating properties in experimental and clinical cancer studies. In our previous works, tesmilifene increased the permeability of the blood-brain barrier (BBB) in animal and culture models. Our aim was to investigate the effects of tesmilifene on brain microvessel permeability in the rat RG2 glioma model and to reveal its mode of action in brain endothelial cells. Tesmilifene significantly increased fluorescein extravasation in the glioma. Short-term treatment with tesmilifene reduced the resistance and increased the permeability for marker molecules in a rat triple co-culture BBB model. Tesmilifene also affected the barrier integrity in brain endothelial cells co-cultured with RG2 glioblastoma cells. Tesmilifene inhibited the activity of P-glycoprotein and multidrug resistance-associated protein-1 efflux pumps and down-regulated the mRNA expression of tight junction proteins, efflux pumps, solute carriers, and metabolic enzymes important for BBB functions. Among the possible signaling pathways that regulate BBB permeability, tesmilifene activated the early nuclear translocation of NFκB. The MAPK/ERK and PI3K/Akt kinase pathways were also involved. We demonstrate for the first time that tesmilifene increases permeability marker molecule extravasation in glioma and inhibits efflux pump activity in brain endothelial cells, which may have therapeutic relevance. Tesmilifene, a chemopotentiator in experimental and clinical cancer studies increases vascular permeability in RG2 glioma in rats and permeability for marker molecules in a culture model of the blood-brain barrier. Tesmilifene inhibits the activity of efflux pumps and down-regulates the mRNA expression of tight junction proteins, transporters, and metabolic enzymes important for the blood-brain barrier functions, which may have therapeutic relevance. PMID:26112237

  5. Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

    PubMed Central

    Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

    2015-01-01

    Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653

  6. Functional Brain Connectivity using fMRI in Aging and Alzheimer’s Disease

    PubMed Central

    Dennis, Emily L.; Thompson, Paul M.

    2014-01-01

    Normal aging and Alzheimer’s disease cause profound changes in the brain’s structure and function. AD in particular is accompanied by widespread cortical neuronal loss, and loss of connections between brain systems. This degeneration of neural pathways disrupts the functional coherence of brain activation. Recent innovations in brain imaging have detected characteristic disruptions in functional networks. Here we review studies examining changes in functional connectivity, measured through fMRI (functional magnetic resonance imaging), starting with healthy aging and then Alzheimer’s disease (AD). We cover studies that employ the three primary methods to analyze functional connectivity – seed-based, ICA (independent components analysis), and graph theory. At the end we include a brief discussion of other methodologies, such as EEG (electroencephalography), MEG (magnetoencephalography), and PET (positron emission tomography). We also describe multi-modal studies that combine rsfMRI (resting state fMRI) with PET imaging, as well as studies examining the effects of medications. Overall, connectivity and network integrity appear to decrease in healthy aging, but this decrease is accelerated in AD, with specific systems hit hardest, such as the default mode network (DMN). Functional connectivity is a relatively new topic of research, but it holds great promise in revealing how brain network dynamics change across the lifespan and in disease. PMID:24562737

  7. Mapping causal functional contributions derived from the clinical assessment of brain damage after stroke

    PubMed Central

    Zavaglia, Melissa; Forkert, Nils D.; Cheng, Bastian; Gerloff, Christian; Thomalla, Götz; Hilgetag, Claus C.

    2015-01-01

    Lesion analysis reveals causal contributions of brain regions to mental functions, aiding the understanding of normal brain function as well as rehabilitation of brain-damaged patients. We applied a novel lesion inference technique based on game theory, Multi-perturbation Shapley value Analysis (MSA), to a large clinical lesion dataset. We used MSA to analyze the lesion patterns of 148 acute stroke patients together with their neurological deficits, as assessed by the National Institutes of Health Stroke Scale (NIHSS). The results revealed regional functional contributions to essential behavioral and cognitive functions as reflected in the NIHSS, particularly by subcortical structures. There were also side specific differences of functional contributions between the right and left hemispheric brain regions which may reflect the dominance of the left hemispheric syndrome aphasia in the NIHSS. Comparison of MSA to established lesion inference methods demonstrated the feasibility of the approach for analyzing clinical data and indicated its capability for objectively inferring functional contributions from multiple injured, potentially interacting sites, at the cost of having to predict the outcome of unknown lesion configurations. The analysis of regional functional contributions to neurological symptoms measured by the NIHSS contributes to the interpretation of this widely used standardized stroke scale in clinical practice as well as clinical trials and provides a first approximation of a ‘map of stroke’. PMID:26448908

  8. Resting-State Functional Connectivity of the Rat Brain

    PubMed Central

    Pawela, Christopher P.; Biswal, Bharat B.; Cho, Younghoon R.; Kao, Dennis S.; Li, Rupeng; Jones, Seth R.; Schulte, Marie L.; Matloub, Hani S.; Hudetz, Anthony G.; Hyde, James S.

    2008-01-01

    Regional-specific average time courses of spontaneous fluctuations in blood oxygen level dependent (BOLD) MRI contrast at 9.4T in lightly anesthetized resting rat brain are formed, and correlation coefficients between time course pairs are interpreted as measures of connectivity. A hierarchy of regional pairwise correlation coefficients (RPCCs) is observed, with the highest values found in the thalamus and cortex, both intra- and interhemisphere, and lower values between cortex and thalamus. Independent sensory networks are distinguished by two methods: data driven, where task activation defines regions of interest (ROI), and hypothesis driven, where regions are defined by the rat histological atlas. Success in these studies is attributed in part to the use of medetomidine hydrochloride (Domitor) for anesthesia. Consistent results in two different rat-brain systems, the sensorimotor and visual, strongly support the hypothesis that resting-state BOLD fluctuations are conserved across mammalian species and can be used to map brain systems. PMID:18429028

  9. Altered functional and structural brain network organization in autism.

    PubMed

    Rudie, J D; Brown, J A; Beck-Pancer, D; Hernandez, L M; Dennis, E L; Thompson, P M; Bookheimer, S Y; Dapretto, M

    2012-01-01

    Structural and functional underconnectivity have been reported for multiple brain regions, functional systems, and white matter tracts in individuals with autism spectrum disorders (ASD). Although recent developments in complex network analysis have established that the brain is a modular network exhibiting small-world properties, network level organization has not been carefully examined in ASD. Here we used resting-state functional MRI (n = 42 ASD, n = 37 typically developing; TD) to show that children and adolescents with ASD display reduced short and long-range connectivity within functional systems (i.e., reduced functional integration) and stronger connectivity between functional systems (i.e., reduced functional segregation), particularly in default and higher-order visual regions. Using graph theoretical methods, we show that pairwise group differences in functional connectivity are reflected in network level reductions in modularity and clustering (local efficiency), but shorter characteristic path lengths (higher global efficiency). Structural networks, generated from diffusion tensor MRI derived fiber tracts (n = 51 ASD, n = 43 TD), displayed lower levels of white matter integrity yet higher numbers of fibers. TD and ASD individuals exhibited similar levels of correlation between raw measures of structural and functional connectivity (n = 35 ASD, n = 35 TD). However, a principal component analysis combining structural and functional network properties revealed that the balance of local and global efficiency between structural and functional networks was reduced in ASD, positively correlated with age, and inversely correlated with ASD symptom severity. Overall, our findings suggest that modeling the brain as a complex network will be highly informative in unraveling the biological basis of ASD and other neuropsychiatric disorders. PMID:24179761

  10. Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain.

    PubMed

    Wong, Becky; Yin, Bin; O'Brien, Beth

    2016-01-01

    Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the "universal" language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics. PMID:26881224

  11. Impact of fatty acids on brain circulation, structure and function.

    PubMed

    Haast, Roy A M; Kiliaan, Amanda J

    2015-01-01

    The use of dietary intervention has evolved into a promising approach to prevent the onset and progression of brain diseases. The positive relationship between intake of omega-3 long chain polyunsaturated fatty acids (ω3-LCPUFAs) and decreased onset of disease- and aging-related deterioration of brain health is increasingly endorsed across epidemiological and diet-interventional studies. Promising results are found regarding to the protection of proper brain circulation, structure and functionality in healthy and diseased humans and animal models. These include enhanced cerebral blood flow (CBF), white and gray matter integrity, and improved cognitive functioning, and are possibly mediated through increased neurovascular coupling, neuroprotection and neuronal plasticity, respectively. Contrary, studies investigating diets high in saturated fats provide opposite results, which may eventually lead to irreversible damage. Studies like these are of great importance given the high incidence of obesity caused by the increased and decreased consumption of respectively saturated fats and ω3-LCPUFAs in the Western civilization. This paper will review in vivo research conducted on the effects of ω3-LCPUFAs and saturated fatty acids on integrity (circulation, structure and function) of the young, aging and diseased brain. PMID:24485516

  12. Cross-hemispheric functional connectivity in the human fetal brain

    PubMed Central

    Thomason, ME; Dassanayake, MT; Shen, S; Katkuri, Y; Alexis, M; Anderson, AL; Yeo, L; Mody, S; Hernandez-Andrade, E; Hassan, SS; Studholme, C; Jeong, JW; Romero, R

    2013-01-01

    Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC. PMID:23427244

  13. Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain

    PubMed Central

    Wong, Becky; Yin, Bin; O'Brien, Beth

    2016-01-01

    Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the “universal” language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics. PMID:26881224

  14. Effects of chronic peripheral olfactory loss on functional brain networks.

    PubMed

    Kollndorfer, K; Jakab, A; Mueller, C A; Trattnig, S; Schöpf, V

    2015-12-01

    The effects of sensory loss on central processing in various sensory systems have already been described. The olfactory system holds the special ability to be activated by a sensorimotor act, without the presentation of an odor. In this study, we investigated brain changes related to chronic peripheral smell loss. We included 11 anosmic patients (eight female, three male; mean age, 43.5 years) with smell loss after an infection of the upper respiratory tract (mean disease duration, 4.64 years) and 14 healthy controls (seven female, seven male; mean age, 30.1 years) in a functional magnetic resonance imaging experiment with a sniffing paradigm. Data were analyzed using group-independent component analysis and functional connectivity analysis. Our results revealed a spatially intact olfactory network in patients, whereas major aberrations due to peripheral loss were observed in functional connectivity through a variety of distributed brain areas. This is the first study to show the re-organization caused by the lack of peripheral input. The results of this study indicate that anosmic patients hold the ability to activate an olfaction-related functional network through the sensorimotor component of odor-perception (sniffing). The areas involved were not different from those that emerged in healthy controls. However, functional connectivity appears to be different between the two groups, with a decrease in functional connectivity in the brain in patients with chronic peripheral sensory loss. We can further conclude that the loss of the sense of smell may induce far-reaching effects in the whole brain, which lead to compensatory mechanisms from other sensory systems due to the close interconnectivity of the olfactory system with other functional networks. PMID:26415766

  15. Antibodies specific for alpha-subunit subtypes of GABAA receptors reveal brain regional heterogeneity.

    PubMed

    Endo, S; Olsen, R W

    1993-04-01

    Antisera were produced in rabbits against synthetic peptides based on subtype-specific regions of the cDNA sequences of the alpha 1, alpha 2, alpha 3, and alpha 4 (also termed alpha 5) subunits of mammalian GABAA receptors. The antigen peptides were chosen from the putative cytoplasmic loop between the proposed third and fourth membrane spanning helices; they were not only subtype-specific sequences, but also their hydrophilicity and predicted secondary structures suggested high potential antigenicity. In all cases, antipeptide antisera recognized on western blots the corresponding alpha-subunit polypeptide of the GABAA receptors purified from bovine brain by benzodiazepine-affinity chromatography, and were able to immunoprecipitate binding activity from detergent-solubilized purified receptors. The four antisera each recognized a unique polypeptide, and only one, in the purified receptor, with alpha 1, alpha 2, alpha 3, and alpha 4 identified at 51, 52, 56, and 57 kDa, respectively. This represents the first identification of the alpha 4 gene product on a gel. Both the relative amount of staining in immunoblots and the fraction of receptor binding that could be immunoprecipitated by saturating concentrations of each of the four subtype-specific antibodies varied in a consistent manner between receptors purified from different brain regions. Thus, cerebral cortex receptor contained all four alpha polypeptides on western blots, and significant activity could be precipitated by all four. Hippocampal receptor lacked alpha 3 immunoreactivity on blotting and by immunoprecipitation; alpha 1 was less, whereas both alpha 2 and alpha 4 were more abundant in hippocampus than in cortex by both techniques. Cerebellum receptor contained only alpha 1 of the four alpha subunits tested, and the anti-alpha 1 antibodies immunoprecipitated > 90% of the binding activity. The variable amounts of staining and immunoprecipitation from the three brain areas by the four antisera demonstrate the presence of heterooligomeric receptor complexes with different alpha-subunit constituents in cortex, hippocampus, and cerebellum. The sum of cortical receptor activity precipitated individually by the four anti-alpha antisera was > 150%, indicating that some heterooligomers are likely to contain more than one class of alpha subtype, although most receptor complexes probably contain only one alpha subtype. These alpha-subunit subtype-specific antibodies should be useful in analyzing structure, function, and localization of GABAA/benzodiazepine receptors in mammalian brain. PMID:8384249

  16. Brain-specific tropomyosins TMBr-1 and TMBr-3 have distinct patterns of expression during development and in adult brain.

    PubMed Central

    Stamm, S; Casper, D; Lees-Miller, J P; Helfman, D M

    1993-01-01

    In this study we report on the developmental and regional expression of two brain-specific isoforms of tropomyosin, TMBr-1 and TMBr-3, that are generated from the rat alpha-tropomyosin gene via the use of alternative promoters and alternative RNA splicing. Western blot analysis using an exon-specific peptide polyclonal antibody revealed that the two isoforms are differentially expressed in development with TMBr-3 appearing in the embryonic brain at 16 days of gestation, followed by the expression of TMBr-1 at 20 days after birth. TMBr-3 was detected in all brain regions examined, whereas TMBr-1 was detected predominantly in brain areas that derived from the prosencephalon. Immunocytochemical studies on mixed primary cultures made from rat embryonic midbrain indicate that expression of the brain-specific epitope is restricted to neurons. The developmental pattern and neuronal localization of these forms of tropomyosin suggest that these isoforms have a specialized role in the development and plasticity of the nervous system. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7694294

  17. A review on functional and structural brain connectivity in numerical cognition

    PubMed Central

    Moeller, Korbinian; Willmes, Klaus; Klein, Elise

    2015-01-01

    Only recently has the complex anatomo-functional system underlying numerical cognition become accessible to evaluation in the living brain. We identified 27 studies investigating brain connectivity in numerical cognition. Despite considerable heterogeneity regarding methodological approaches, populations investigated, and assessment procedures implemented, the results provided largely converging evidence regarding the underlying brain connectivity involved in numerical cognition. Analyses of both functional/effective as well as structural connectivity have consistently corroborated the assumption that numerical cognition is subserved by a fronto-parietal network including (intra)parietal as well as (pre)frontal cortex sites. Evaluation of structural connectivity has indicated the involvement of fronto-parietal association fibers encompassing the superior longitudinal fasciculus dorsally and the external capsule/extreme capsule system ventrally. Additionally, commissural fibers seem to connect the bilateral intraparietal sulci when number magnitude information is processed. Finally, the identification of projection fibers such as the superior corona radiata indicates connections between cortex and basal ganglia as well as the thalamus in numerical cognition. Studies on functional/effective connectivity further indicated a specific role of the hippocampus. These specifications of brain connectivity augment the triple-code model of number processing and calculation with respect to how gray matter areas associated with specific number-related representations may work together. PMID:26029075

  18. Partial sleep in the context of augmentation of brain function

    PubMed Central

    Pigarev, Ivan N.; Pigareva, Marina L.

    2014-01-01

    Inability to solve complex problems or errors in decision making is often attributed to poor brain processing, and raises the issue of brain augmentation. Investigation of neuronal activity in the cerebral cortex in the sleep-wake cycle offers insights into the mechanisms underlying the reduction in mental abilities for complex problem solving. Some cortical areas may transit into a sleep state while an organism is still awake. Such local sleep would reduce behavioral ability in the tasks for which the sleeping areas are crucial. The studies of this phenomenon have indicated that local sleep develops in high order cortical areas. This is why complex problem solving is mostly affected by local sleep, and prevention of local sleep might be a potential way of augmentation of brain function. For this approach to brain augmentation not to entail negative consequences for the organism, it is necessary to understand the functional role of sleep. Our studies have given an unexpected answer to this question. It was shown that cortical areas that process signals from extero- and proprioreceptors during wakefulness, switch to the processing of interoceptive information during sleep. It became clear that during sleep all “computational power” of the brain is directed to the restoration of the vital functions of internal organs. These results explain the logic behind the initiation of total and local sleep. Indeed, a mismatch between the current parameters of any visceral system and the genetically determined normal range would provide the feeling of tiredness, or sleep pressure. If an environmental situation allows falling asleep, the organism would transit to a normal total sleep in all cortical areas. However, if it is impossible to go to sleep immediately, partial sleep may develop in some cortical areas in the still behaviorally awake organism. This local sleep may reduce both the “intellectual power” and the restorative function of sleep for visceral organs. PMID:24822040

  19. The brain-specific Beta4 subunit downregulates BK channel cell surface expression.

    PubMed

    Shruti, Sonal; Urban-Ciecko, Joanna; Fitzpatrick, James A; Brenner, Robert; Bruchez, Marcel P; Barth, Alison L

    2012-01-01

    The large-conductance K(+) channel (BK channel) can control neural excitability, and enhanced channel currents facilitate high firing rates in cortical neurons. The brain-specific auxiliary subunit β4 alters channel Ca(++)- and voltage-sensitivity, and β4 knock-out animals exhibit spontaneous seizures. Here we investigate β4's effect on BK channel trafficking to the plasma membrane. Using a novel genetic tag to track the cellular location of the pore-forming BKα subunit in living cells, we find that β4 expression profoundly reduces surface localization of BK channels via a C-terminal ER retention sequence. In hippocampal CA3 neurons from C57BL/6 mice with endogenously high β4 expression, whole-cell BK channel currents display none of the characteristic properties of BKα+β4 channels observed in heterologous cells. Finally, β4 knock-out animals exhibit a 2.5-fold increase in whole-cell BK channel current, indicating that β4 also regulates current magnitude in vivo. Thus, we propose that a major function of the brain-specific β4 subunit in CA3 neurons is control of surface trafficking. PMID:22438928

  20. Gender-associated differential expression of cytokines in specific areas of the brain during helminth infection.

    PubMed

    López-Griego, Lorena; Nava-Castro, Karen Elizabeth; López-Salazar, Valeria; Hernández-Cervantes, Rosalía; Tiempos Guzmán, Nelly; Muñiz-Hernández, Saé; Hernández-Bello, Romel; Besedovsky, Hugo O; Pavón, Lenin; Becerril Villanueva, Luis Enrique; Morales-Montor, Jorge

    2015-02-01

    Intraperitoneal infection with Taenia crassiceps cysticerci in mice alters several behaviors, including sexual, aggressive, and cognitive function. Cytokines and their receptors are produced in the central nervous system (CNS) by specific neural cell lineages under physiological and pathological conditions, regulating such processes as neurotransmission. This study is aimed to determine the expression patterns of cytokines in various areas of the brain in normal and T. crassiceps-infected mice in both genders and correlate them with the pathology of the CNS and parasite counts. IL-4, IFN-γ, and TNF-α levels in the hippocampus and olfactory bulb increased significantly in infected male mice, but IL-6 was downregulated in these regions in female mice. IL-1β expression in the hippocampus was unaffected by infection in either gender. Our novel findings demonstrate a clear gender-associated pattern of cytokine expression in specific areas of the brain in mammals that parasitic infection can alter. Thus, we hypothesize that intraperitoneal infection is sensed by the CNS of the host, wherein cytokines are important messengers in the host-parasite neuroimmunoendocrine network. PMID:25495255

  1. Gender-Associated Differential Expression of Cytokines in Specific Areas of the Brain During Helminth Infection

    PubMed Central

    López-Griego, Lorena; Nava-Castro, Karen Elizabeth; López-Salazar, Valeria; Hernández-Cervantes, Rosalía; Tiempos Guzmán, Nelly; Muñiz-Hernández, Saé; Hernández-Bello, Romel; Besedovsky, Hugo O.; Pavón, Lenin; Becerril Villanueva, Luis Enrique

    2015-01-01

    Intraperitoneal infection with Taenia crassiceps cysticerci in mice alters several behaviors, including sexual, aggressive, and cognitive function. Cytokines and their receptors are produced in the central nervous system (CNS) by specific neural cell lineages under physiological and pathological conditions, regulating such processes as neurotransmission. This study is aimed to determine the expression patterns of cytokines in various areas of the brain in normal and T. crassiceps-infected mice in both genders and correlate them with the pathology of the CNS and parasite counts. IL-4, IFN-γ, and TNF-α levels in the hippocampus and olfactory bulb increased significantly in infected male mice, but IL-6 was downregulated in these regions in female mice. IL-1β expression in the hippocampus was unaffected by infection in either gender. Our novel findings demonstrate a clear gender-associated pattern of cytokine expression in specific areas of the brain in mammals that parasitic infection can alter. Thus, we hypothesize that intraperitoneal infection is sensed by the CNS of the host, wherein cytokines are important messengers in the host–parasite neuroimmunoendocrine network. PMID:25495255

  2. Two distinct forms of functional lateralization in the human brain

    PubMed Central

    Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex

    2013-01-01

    The hemispheric lateralization of certain faculties in the human brain has long been held to be beneficial for functioning. However, quantitative relationships between the degree of lateralization in particular brain regions and the level of functioning have yet to be established. Here we demonstrate that two distinct forms of functional lateralization are present in the left vs. the right cerebral hemisphere, with the left hemisphere showing a preference to interact more exclusively with itself, particularly for cortical regions involved in language and fine motor coordination. In contrast, right-hemisphere cortical regions involved in visuospatial and attentional processing interact in a more integrative fashion with both hemispheres. The degree of lateralization present in these distinct systems selectively predicted behavioral measures of verbal and visuospatial ability, providing direct evidence that lateralization is associated with enhanced cognitive ability. PMID:23959883

  3. Gender and brain regions specific differences in brain derived neurotrophic factor protein levels of depressed individuals who died through suicide.

    PubMed

    Hayley, Shawn; Du, Lisheng; Litteljohn, Darcy; Palkovits, Miklós; Faludi, Gábor; Merali, Zul; Poulter, Michael O; Anisman, Hymie

    2015-07-23

    Considerable evidence supports the view that depressive illness and suicidal behaviour stem from perturbations of neuroplasticity. Presently, we assessed whether depressed individuals who died by suicide displayed brain region-specific changes in brain derived neurotrophic factor (BDNF) and whether such effects varied by gender. Using postmortem samples from non-psychiatric controls and depressed individuals who died by suicide, BDNF protein levels were assessed within the hippocampus and frontopolar prefrontal cortex using Western blot. As expected, BDNF levels were reduced within the frontopolar prefrontal cortex among female depressed suicides; however, males showed no such effect. Contrastingly, within the hippocampus, depressed male but not female suicides displayed significant reductions of BDNF protein levels. Although the mechanisms driving the gender and brain region specific BDNF changes are unclear, our data do support the notion that complex alterations of neuroplasticity may be fundamentally involved in the illness. PMID:26033186

  4. Exercise-mimetic AICAR transiently benefits brain function.

    PubMed

    Guerrieri, Davide; van Praag, Henriette

    2015-07-30

    Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP-kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function. PMID:26286955

  5. Exercise-mimetic AICAR transiently benefits brain function

    PubMed Central

    Guerrieri, Davide; van Praag, Henriette

    2015-01-01

    Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP-kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function. PMID:26286955

  6. Genetic Architecture of Subcortical Brain Regions: Common and Region-Specific Genetic Contributions

    PubMed Central

    Rentería, Miguel E.; Hansell, Narelle K.; Strike, Lachlan T.; McMahon, Katie L.; de Zubicaray, Greig I.; Hickie, Ian B.; Thompson, Paul M.; Martin, Nicholas G.; Medland, Sarah E.; Wright, Margaret J.

    2014-01-01

    Understanding the etiology of patterns of variation within and covariation across brain regions is key to advancing our understanding of the functional, anatomical and developmental networks of the brain. Here we applied multivariate twin modeling and principal component analysis (PCA) to investigate the genetic architecture of the size of seven subcortical regions (caudate nucleus, thalamus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens) in a genetically informative sample of adolescents and young adults (N=1,038; mean age=21.6 ± 3.2 years; including 148 monozygotic and 202 dizygotic twin pairs) from the Queensland Twin IMaging (QTIM) Study. Our multivariate twin modeling identified a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In addition, we also found substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52). This provides further insight into the extent and organization of multiple genetic factors, which include developmental and general growth pathways, as well as functional specialization and maturation trajectories that influence each subcortical region. PMID:25199620

  7. WONOEP APPRAISAL: NEW SYSTEMIC FUNCTIONAL IMAGING TECHNOLOGIES TO STUDY THE BRAIN IN EXPERIMENTAL MODELS OF EPILEPSY

    PubMed Central

    Dedeurwaerdere, Stefanie; Shultz, Sandy R.; Federico, Paolo; Engel, Jerome

    2014-01-01

    Summary Objectives Modern functional neuroimaging provides opportunities to visualize activity of the entire brain, making it an indispensable diagnostic tool for epilepsy. Various forms of non-invasive functional neuroimaging are now also being performed as research tools in animal models of epilepsy and provide opportunities for parallel animal/human investigations into fundamental mechanisms of epilepsy and identification of epilepsy biomarkers. Methods Recent animal studies of epilepsy using positron emission tomography, tractography, and functional magnetic resonance imaging were reviewed. Results Epilepsy is an abnormal emergent property of disturbances in neuronal networks which, even for epilepsies characterized by focal seizures, involve widely distributed systems, often in both hemispheres. Functional neuroimaging in animal models now provides opportunities to examine neuronal disturbances in the whole brain that underlie generalized and focal seizure generation as well as various types of epileptogenesis. Significance Tremendous advances in understanding the contribution of specific properties of widely distributed neuronal networks to both normal and abnormal human behavior have been provided by current functional neuroimaging methodologies. Successful application of functional neuroimaging of the whole brain in the animal laboratory now permits investigations during epileptogenesis and correlation with deep brain EEG activity. With the continuing development of these techniques and analytical methods, the potential for future translational research on epilepsy is enormous. PMID:24836499

  8. Whole-brain functional hypoconnectivity as an endophenotype of autism in adolescents

    PubMed Central

    Moseley, R.L.; Ypma, R.J.F.; Holt, R.J.; Floris, D.; Chura, L.R.; Spencer, M.D.; Baron-Cohen, S.; Suckling, J.; Bullmore, E.; Rubinov, M.

    2015-01-01

    Endophenotypes are heritable and quantifiable markers that may assist in the identification of the complex genetic underpinnings of psychiatric conditions. Here we examined global hypoconnectivity as an endophenotype of autism spectrum conditions (ASCs). We studied well-matched groups of adolescent males with autism, genetically-related siblings of individuals with autism, and typically-developing control participants. We parcellated the brain into 258 regions and used complex-network analysis to detect a robust hypoconnectivity endophenotype in our participant group. We observed that whole-brain functional connectivity was highest in controls, intermediate in siblings, and lowest in ASC, in task and rest conditions. We identified additional, local endophenotype effects in specific networks including the visual processing and default mode networks. Our analyses are the first to show that whole-brain functional hypoconnectivity is an endophenotype of autism in adolescence, and may thus underlie the heritable similarities seen in adolescents with ASC and their relatives. PMID:26413477

  9. Identification of brain-specific angiogenesis inhibitor 2 as an interaction partner of glutaminase interacting protein

    SciTech Connect

    Zencir, Sevil; Ovee, Mohiuddin; Dobson, Melanie J.; Banerjee, Monimoy; Topcu, Zeki; Mohanty, Smita

    2011-08-12

    Highlights: {yields} Brain-specific angiogenesis inhibitor 2 (BAI2) is a new partner protein for GIP. {yields} BAI2 interaction with GIP was revealed by yeast two-hybrid assay. {yields} Binding of BAI2 to GIP was characterized by NMR, CD and fluorescence. {yields} BAI2 and GIP binding was mediated through the C-terminus of BAI2. -- Abstract: The vast majority of physiological processes in living cells are mediated by protein-protein interactions often specified by particular protein sequence motifs. PDZ domains, composed of 80-100 amino acid residues, are an important class of interaction motif. Among the PDZ-containing proteins, glutaminase interacting protein (GIP), also known as Tax Interacting Protein TIP-1, is unique in being composed almost exclusively of a single PDZ domain. GIP has important roles in cellular signaling, protein scaffolding and modulation of tumor growth and interacts with a number of physiological partner proteins, including Glutaminase L, {beta}-Catenin, FAS, HTLV-1 Tax, HPV16 E6, Rhotekin and Kir 2.3. To identify the network of proteins that interact with GIP, a human fetal brain cDNA library was screened using a yeast two-hybrid assay with GIP as bait. We identified brain-specific angiogenesis inhibitor 2 (BAI2), a member of the adhesion-G protein-coupled receptors (GPCRs), as a new partner of GIP. BAI2 is expressed primarily in neurons, further expanding GIP cellular functions. The interaction between GIP and the carboxy-terminus of BAI2 was characterized using fluorescence, circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy assays. These biophysical analyses support the interaction identified in the yeast two-hybrid assay. This is the first study reporting BAI2 as an interaction partner of GIP.

  10. Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

    PubMed

    Wichmann, Thomas; DeLong, Mahlon R

    2016-04-01

    Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks. PMID:26956115

  11. Structural and functional brain changes in delusional disorder.

    PubMed

    Vicens, Victor; Radua, Joaquim; Salvador, Raymond; Anguera-Camós, Maria; Canales-Rodríguez, Erick J; Sarró, Salvador; Maristany, Teresa; McKenna, Peter J; Pomarol-Clotet, Edith

    2016-02-01

    BackgroundDelusional disorder has been the subject of very little investigation using brain imaging.AimsTo examine potential structural and/or functional brain abnormalities in this disorder.MethodWe used structural imaging (voxel-based morphometry, VBM) and functional imaging (during performance of the n-back task and whole-brain resting connectivity analysis) to examine 22 patients meeting DSM-IV criteria for delusional disorder and 44 matched healthy controls.ResultsThe patients showed grey matter reductions in the medial frontal/anterior cingulate cortex and bilateral insula on unmodulated (but not on modulated) VBM analysis, failure of de-activation in the medial frontal/anterior cingulate cortex during performance of the n-back task, and decreased resting-state connectivity in the bilateral insula.ConclusionsThe findings provide evidence of brain abnormality in the medial frontal/anterior cingulate cortex and insula in delusional disorder. A role for the former region in the pathogenesis of delusions is consistent with several other lines of evidence. PMID:26382955

  12. Sleep Restriction Impairs Blood–Brain Barrier Function

    PubMed Central

    He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J.; Wang, Yuping

    2014-01-01

    The blood–brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. PMID:25355222

  13. Functional brain networks associated with eating behaviors in obesity.

    PubMed

    Park, Bo-Yong; Seo, Jongbum; Park, Hyunjin

    2016-01-01

    Obesity causes critical health problems including diabetes and hypertension that affect billions of people worldwide. Obesity and eating behaviors are believed to be closely linked but their relationship through brain networks has not been fully explored. We identified functional brain networks associated with obesity and examined how the networks were related to eating behaviors. Resting state functional magnetic resonance imaging (MRI) scans were obtained for 82 participants. Data were from an equal number of people of healthy weight (HW) and non-healthy weight (non-HW). Connectivity matrices were computed with spatial maps derived using a group independent component analysis approach. Brain networks and associated connectivity parameters with significant group-wise differences were identified and correlated with scores on a three-factor eating questionnaire (TFEQ) describing restraint, disinhibition, and hunger eating behaviors. Frontoparietal and cerebellum networks showed group-wise differences between HW and non-HW groups. Frontoparietal network showed a high correlation with TFEQ disinhibition scores. Both frontoparietal and cerebellum networks showed a high correlation with body mass index (BMI) scores. Brain networks with significant group-wise differences between HW and non-HW groups were identified. Parts of the identified networks showed a high correlation with eating behavior scores. PMID:27030024

  14. Functional brain networks associated with eating behaviors in obesity

    PubMed Central

    Park, Bo-yong; Seo, Jongbum; Park, Hyunjin

    2016-01-01

    Obesity causes critical health problems including diabetes and hypertension that affect billions of people worldwide. Obesity and eating behaviors are believed to be closely linked but their relationship through brain networks has not been fully explored. We identified functional brain networks associated with obesity and examined how the networks were related to eating behaviors. Resting state functional magnetic resonance imaging (MRI) scans were obtained for 82 participants. Data were from an equal number of people of healthy weight (HW) and non-healthy weight (non-HW). Connectivity matrices were computed with spatial maps derived using a group independent component analysis approach. Brain networks and associated connectivity parameters with significant group-wise differences were identified and correlated with scores on a three-factor eating questionnaire (TFEQ) describing restraint, disinhibition, and hunger eating behaviors. Frontoparietal and cerebellum networks showed group-wise differences between HW and non-HW groups. Frontoparietal network showed a high correlation with TFEQ disinhibition scores. Both frontoparietal and cerebellum networks showed a high correlation with body mass index (BMI) scores. Brain networks with significant group-wise differences between HW and non-HW groups were identified. Parts of the identified networks showed a high correlation with eating behavior scores. PMID:27030024

  15. Intestinal barrier function and the brain-gut axis.

    PubMed

    Alonso, Carmen; Vicario, María; Pigrau, Marc; Lobo, Beatriz; Santos, Javier

    2014-01-01

    The luminal-mucosal interface of the intestinal tract is the first relevant location where microorganism-derived antigens and all other potentially immunogenic particles face the scrutiny of the powerful mammalian immune system. Upon regular functioning conditions, the intestinal barrier is able to effectively prevent most environmental and external antigens to interact openly with the numerous and versatile elements that compose the mucosal-associated immune system. This evolutionary super system is capable of processing an astonishing amount of antigens and non-immunogenic particles, approximately 100 tons in one individual lifetime, only considering food-derived components. Most important, to develop oral tolerance and proper active immune responses needed to prevent disease and inflammation, this giant immunogenic load has to be managed in a way that physiological inflammatory balance is constantly preserved. Adequate functioning of the intestinal barrier involves local and distant regulatory networks integrating the so-called brain-gut axis. Along this complex axis both brain and gut structures participate in the processing and execution of response signals to external and internal changes coming from the digestive tract, using multidirectional pathways to communicate. Dysfunction of brain-gut axis facilitates malfunctioning of the intestinal barrier, and vice versa, increasing the risk of uncontrolled immunological reactions that may trigger mucosal and brain low-grade inflammation, a putative first step to the initiation of more permanent gut disorders. In this chapter, we describe the structure, function and interactions of intestinal barrier, microbiota and brain-gut axis in both healthy and pathological conditions. PMID:24997030

  16. Brain Region-Specific Trafficking of the Dopamine Transporter

    PubMed Central

    Block, Ethan R.; Nuttle, Jacob; Balcita-Pedicino, Judith Joyce; Caltagarone, John; Watkins, Simon C.

    2015-01-01

    The dopamine (DA) transporter (DAT) controls dopaminergic neurotransmission by removing extracellular DA. Although DA reuptake is proposed to be regulated by DAT traffic to and from the cell surface, the membrane trafficking system involved in the endocytic cycling of DAT in the intact mammalian brain has not been characterized. Hence, we performed immunolabeling and quantitative analysis of the subcellular and regional distribution of DAT using the transgenic knock-in mouse expressing hemagglutinin (HA) epitope-tagged DAT (HA-DAT) and by using a combination of electron microscopy and a novel method for immunofluorescence labeling of HA-DAT in acute sagittal brain slices. Both approaches demonstrated that, in midbrain somatodendritic regions, HA-DAT was present in the plasma membrane, endoplasmic reticulum, and Golgi complex, with a small fraction in early and recycling endosomes and an even smaller fraction in late endosomes and lysosomes. In the striatum and in axonal tracts between the midbrain and striatum, HA-DAT was detected predominantly in the plasma membrane, and quantitative analysis revealed increased DAT density in striatal compared with midbrain plasma membranes. Endosomes were strikingly rare and lysosomes were absent in striatal axons, in which there was little intracellular HA-DAT. Acute administration of amphetamine in vivo (60 min) or to slices ex vivo (10–60 min) did not result in detectable changes in DAT distribution. Altogether, these data provide evidence for regional differences in DAT plasma membrane targeting and retention and suggest a surprisingly low level of endocytic trafficking of DAT in the striatum along with limited DAT endocytic activity in somatodendritic areas. SIGNIFICANCE STATEMENT The dopamine transporter (DAT) is the key regulator of the dopamine neurotransmission in the CNS. In the present study, we developed a new approach for studying DAT localization and dynamics in intact neurons in acute sagittal brain slices from the knock-in mouse expressing epitope-tagged DAT. For the first time, the fluorescence imaging analysis of DAT was combined with the immunogold labeling of DAT and quantitative electron microscopy. In contrast to numerous studies of DAT trafficking in heterologous expression systems and dissociated cultured neurons, studies in intact neurons revealed a surprisingly low amount of endocytic trafficking of DAT at steady state and after acute amphetamine treatment and suggested that non-vesicular transport could be the main mechanism establishing DAT distribution within the dopaminergic neuron. PMID:26377471

  17. Transcranial brain stimulation to promote functional recovery after stroke

    PubMed Central

    Raffin, Estelle; Siebner, Hartwig R.

    2014-01-01

    Purpose of review Noninvasive brain stimulation (NIBS) is increasingly used to enhance the recovery of function after stroke. The purpose of this review is to highlight and discuss some unresolved questions that need to be addressed to better understand and exploit the potential of NIBS as a therapeutic tool. Recent findings Recent meta-analyses showed that the treatment effects of NIBS in patients with stroke are rather inconsistent across studies and the evidence for therapeutic efficacy is still uncertain. This raises the question of how NIBS can be developed further to improve its therapeutic efficacy. Summary This review addressed six questions: How does NIBS facilitate the recovery of function after stroke? Which brain regions should be targeted by NIBS? Is there a particularly effective NIBS modality that should be used? Does the location of the stroke influence the therapeutic response? How often should NIBS be repeated? Is the functional state of the brain during or before NIBS relevant to therapeutic efficacy of NIBS? We argue that these questions need to be tackled to obtain sufficient mechanistic understanding of how NIBS facilitates the recovery of function. This knowledge will be critical to fully unfold the therapeutic effects of NIBS and will pave the way towards adaptive NIBS protocols, in which NIBS is tailored to the individual patient. PMID:24296641

  18. Homeostatic control of brain function - new approaches to understand epileptogenesis.

    PubMed

    Boison, Detlev; Sandau, Ursula S; Ruskin, David N; Kawamura, Masahito; Masino, Susan A

    2013-01-01

    Neuronal excitability of the brain and ongoing homeostasis depend not only on intrinsic neuronal properties, but also on external environmental factors; together these determine the functionality of neuronal networks. Homeostatic factors become critically important during epileptogenesis, a process that involves complex disruption of self-regulatory mechanisms. Here we focus on the bioenergetic homeostatic network regulator adenosine, a purine nucleoside whose availability is largely regulated by astrocytes. Endogenous adenosine modulates complex network function through multiple mechanisms including adenosine receptor-mediated pathways, mitochondrial bioenergetics, and adenosine receptor-independent changes to the epigenome. Accumulating evidence from our laboratories shows that disruption of adenosine homeostasis plays a major role in epileptogenesis. Conversely, we have found that reconstruction of adenosine's homeostatic functions provides new hope for the prevention of epileptogenesis. We will discuss how adenosine-based therapeutic approaches may interfere with epileptogenesis on an epigenetic level, and how dietary interventions can be used to restore network homeostasis in the brain. We conclude that reconstruction of homeostatic functions in the brain offers a new conceptual advance for the treatment of neurological conditions which goes far beyond current target-centric treatment approaches. PMID:23882181

  19. Functional magnetic resonance imaging of mild traumatic brain injury.

    PubMed

    Mayer, Andrew R; Bellgowan, Patrick S F; Hanlon, Faith M

    2015-02-01

    Functional magnetic resonance imaging (fMRI) offers great promise for elucidating the neuropathology associated with a single or repetitive mild traumatic brain injury (mTBI). The current review discusses the physiological underpinnings of the blood-oxygen level dependent response and how trauma affects the signal. Methodological challenges associated with fMRI data analyses are considered next, followed by a review of current mTBI findings. The majority of evoked studies have examined working memory and attentional functioning, with results suggesting a complex relationship between cognitive load/attentional demand and neuronal activation. Researchers have more recently investigated how brain trauma affects functional connectivity, and the benefits/drawbacks of evoked and functional connectivity studies are also discussed. The review concludes by discussing the major clinical challenges associated with fMRI studies of brain-injured patients, including patient heterogeneity and variations in scan-time post-injury. We conclude that the fMRI signal represents a complex filter through which researchers can measure the physiological correlates of concussive symptoms, an important goal for the burgeoning field of mTBI research. PMID:25434880

  20. [Mental function, functional hierarchy of the brain and glucoregulation].

    PubMed

    Dejours, C; Assan, R; Tassin, J P

    1983-01-01

    Mental function in insulin-dependent diabetic (IDD) patients can be correlated with the endocrine and metabolic symptoms and signs of anxiety. In IDD patients, anxiety is usually accompanied by hyperactivity of the hyperglycemic hypothalamo-visceral axis. The hypothalamus is controlled by different superior nervous structures (limbic system and cortex) which, themselves, receive dopaminergic afferences. Two main patterns of reaction to anxiety associated with two distinct patterns of hypothalamo-visceral reactions, are suggested. In one, excessive hypothalamo-visceral reactions to stress can be associated with a deficient control of the hypothalamus. In the other, an appropriate control of the hypothalamus by limbic systems and prefrontal systems, via dopaminergic pathways, reduces the hyperglycemic reaction to stress. According to a psychosomatic approach, the principles of which are briefly recalled, some characterisation of mental function in IDD patients can be defined, as well as its psychiatric presentation. An improvement in mental function can be associated with a reduction in hypothalamic responses to the external or internal stimuli. An improvement in metabolic control can follow psychotherapy in such patients. Central dopaminergic pathways may play an important role in the control of anxiety and the subsequent endocrine and metabolic disorders caused by stress. PMID:6347659

  1. Mining topological structures of protein-protein interaction networks for human brain-specific genes.

    PubMed

    Cui, W J; Gong, X J; Yu, H; Zhang, X C

    2015-01-01

    Compared to other placental mammals, humans have unique thinking and cognitive abilities because of their developed cerebral cortex composed of billions of neurons and synaptic connections. As the primary effectors of the mechanisms of life, proteins and their interactions form the basis of cellular and molecular functions in the living body. In this paper, we developed a pipeline for mining topological structures, identifying functional modules, and analyzing their functions from publically available datasets. A human brain-specific protein-protein interaction network with 1482 nodes and 3105 edges was built using a MapReduce based shortest path algorithm. Within this, 7 functional cliques were identified using a network clustering method, 98 hub proteins were obtained by the calculation of betweenness and connectivity, and 5 closest relationship to clique connector proteins were recognized by the combination scores of topological distance and gene ontology similarity. Furthermore, we discovered functional modules interacting with TP53 protein, which involves several fragmented research study conclusions and might be an important clue for further in vivo or in silico experiments to confirm these associations. PMID:26505393

  2. Resting-state functional brain connectivity: lessons from functional near-infrared spectroscopy.

    PubMed

    Niu, Haijing; He, Yong

    2014-04-01

    Resting-state functional near-infrared spectroscopy (R-fNIRS) is an active area of interest and is currently attracting considerable attention as a new imaging tool for the study of resting-state brain function. Using variations in hemodynamic concentration signals, R-fNIRS measures the brain's low-frequency spontaneous neural activity, combining the advantages of portability, low-cost, high temporal sampling rate and less physical burden to participants. The temporal synchronization of spontaneous neuronal activity in anatomically separated regions is referred to as resting-state functional connectivity (RSFC). In the past several years, an increasing body of R-fNIRS RSFC studies has led to many important findings about functional integration among local or whole-brain regions by measuring inter-regional temporal synchronization. Here, we summarize recent advances made in the R-fNIRS RSFC methodologies, from the detection of RSFC (e.g., seed-based correlation analysis, independent component analysis, whole-brain correlation analysis, and graph-theoretical topological analysis), to the assessment of RSFC performance (e.g., reliability, repeatability, and validity), to the application of RSFC in studying normal development and brain disorders. The literature reviewed here suggests that RSFC analyses based on R-fNIRS data are valid and reliable for the study of brain function in healthy and diseased populations, thus providing a promising imaging tool for cognitive science and clinics. PMID:24022325

  3. Control channels in the brain and their influence on brain executive functions

    NASA Astrophysics Data System (ADS)

    Meng, Qinglei; Choa, Fow-Sen; Hong, Elliot; Wang, Zhiguang; Islam, Mohammad

    2014-05-01

    In a computer network there are distinct data channels and control channels where massive amount of visual information are transported through data channels but the information streams are routed and controlled by intelligent algorithm through "control channels". Recent studies on cognition and consciousness have shown that the brain control channels are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person's brain using binaural beats technique and identify the individual's preferred control channels. The identified control channels can then be used to influence the subject's brain executive functions. In the experiment, an EEG measurement system was used to record and identify a subject's control channels. After these channels were identified, the subject was asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject's brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the subject's executive function performance and reduced the time to complete incongruent tests, while the alpha signal didn't seem to be able to slow down the executive function performance.

  4. Sharing self-related information is associated with intrinsic functional connectivity of cortical midline brain regions

    PubMed Central

    Meshi, Dar; Mamerow, Loreen; Kirilina, Evgeniya; Morawetz, Carmen; Margulies, Daniel S.; Heekeren, Hauke R.

    2016-01-01

    Human beings are social animals and they vary in the degree to which they share information about themselves with others. Although brain networks involved in self-related cognition have been identified, especially via the use of resting-state experiments, the neural circuitry underlying individual differences in the sharing of self-related information is currently unknown. Therefore, we investigated the intrinsic functional organization of the brain with respect to participants’ degree of self-related information sharing using resting state functional magnetic resonance imaging and self-reported social media use. We conducted seed-based correlation analyses in cortical midline regions previously shown in meta-analyses to be involved in self-referential cognition: the medial prefrontal cortex (MPFC), central precuneus (CP), and caudal anterior cingulate cortex (CACC). We examined whether and how functional connectivity between these regions and the rest of the brain was associated with participants’ degree of self-related information sharing. Analyses revealed associations between the MPFC and right dorsolateral prefrontal cortex (DLPFC), as well as the CP with the right DLPFC, the left lateral orbitofrontal cortex and left anterior temporal pole. These findings extend our present knowledge of functional brain connectivity, specifically demonstrating how the brain’s intrinsic functional organization relates to individual differences in the sharing of self-related information. PMID:26948055

  5. Understanding structural-functional relationships in the human brain: a large-scale network perspective.

    PubMed

    Wang, Zhijiang; Dai, Zhengjia; Gong, Gaolang; Zhou, Changsong; He, Yong

    2015-06-01

    Relating the brain's structural connectivity (SC) to its functional connectivity (FC) is a fundamental goal in neuroscience because it is capable of aiding our understanding of how the relatively fixed SC architecture underlies human cognition and diverse behaviors. With the aid of current noninvasive imaging technologies (e.g., structural MRI, diffusion MRI, and functional MRI) and graph theory methods, researchers have modeled the human brain as a complex network of interacting neuronal elements and characterized the underlying structural and functional connectivity patterns that support diverse cognitive functions. Specifically, research has demonstrated a tight SC-FC coupling, not only in interregional connectivity strength but also in network topologic organizations, such as community, rich-club, and motifs. Moreover, this SC-FC coupling exhibits significant changes in normal development and neuropsychiatric disorders, such as schizophrenia and epilepsy. This review summarizes recent progress regarding the SC-FC relationship of the human brain and emphasizes the important role of large-scale brain networks in the understanding of structural-functional associations. Future research directions related to this topic are also proposed. PMID:24962094

  6. Whole brain functional connectivity using phase locking measures of resting state magnetoencephalography

    PubMed Central

    Schmidt, Benjamin T.; Ghuman, Avniel S.; Huppert, Theodore J.

    2014-01-01

    The analysis of spontaneous functional connectivity (sFC) reveals the statistical connections between regions of the brain consistent with underlying functional communication networks within the brain. In this work, we describe the implementation of a complete all-to-all network analysis of resting state neuronal activity from magnetoencephalography (MEG). Using graph theory to define networks at the dipole level, we established functionally defined regions by k-means clustering cortical surface locations using Eigenvector centrality (EVC) scores from the all-to-all adjacency model. Permutation testing was used to estimate regions with statistically significant connections compared to empty room data, which adjusts for spatial dependencies introduced by the MEG inverse problem. In order to test this model, we performed a series of numerical simulations investigating the effects of the MEG reconstruction on connectivity estimates. We subsequently applied the approach to subject data to investigate the effectiveness of our method in obtaining whole brain networks. Our findings indicated that our model provides statistically robust estimates of functional region networks. Application of our phase locking network methodology to real data produced networks with similar connectivity to previously published findings, specifically, we found connections between contralateral areas of the arcuate fasciculus that have been previously investigated. The use of data-driven methods for neuroscientific investigations provides a new tool for researchers in identifying and characterizing whole brain functional connectivity networks. PMID:25018690

  7. A biomedical information system for neuroimaging and brain function

    NASA Astrophysics Data System (ADS)

    You, Jun; Zhang, Jie; Luo, Qingming

    2007-05-01

    In order to solve the database interoperability and neuroscientific information integration, we have built an internet-accessible Biomedical Information System (BMIS) for neuroimaging and brain function research. BMIS is a multi-purpose academic periodical full-text literature platform; it safeguards the literature involving Neuroscience, Biomedical Photonics, Medical Imaging, Bioinformatics and so on, and can carry on the input, retrieval and maintenance of the literature data. Based on the cluster system of TS10000 and new data processing technologies, the establishment of this integrated, individualized and extensible system will provide the massive data set needed for knowledge discovery and will serve as a foundation for future hypothesis-driven experiments, which begin with a special problem of substantial scientific interest about neuroimaging and brain function.

  8. Control of Brain Development, Function, and Behavior by the Microbiome

    PubMed Central

    Sampson, Timothy R.; Mazmanian, Sarkis K.

    2015-01-01

    Animals share an intimate and life-long partnership with a myriad of resident microbial species, collectively referred to as the microbiota. Symbiotic microbes have been shown to regulate nutrition and metabolism, and are critical for the development and function of the immune system. More recently, studies have suggested that gut bacteria can impact neurological outcomes – altering behavior and potentially affecting the onset and/or severity of nervous system disorders. In this review, we highlight emerging evidence that the microbiome extends its influence to the brain via various pathways connecting the gut to the central nervous system. While understanding and appreciation of a gut microbial impact on neurological function is nascent, unraveling gut-microbiome-brain connections holds the promise of transforming the neurosciences and revealing potentially novel etiologies for psychiatric and neurodegenerative disorders. PMID:25974299

  9. Global features of functional brain networks change with contextual disorder.

    PubMed

    Andric, Michael; Hasson, Uri

    2015-08-15

    It is known that features of stimuli in the environment affect the strength of functional connectivity in the human brain. However, investigations to date have not converged in determining whether these also impact functional networks' global features, such as modularity strength, number of modules, partition structure, or degree distributions. We hypothesized that one environmental attribute that may strongly impact global features is the temporal regularity of the environment, as prior work indicates that differences in regularity impact regions involved in sensory, attentional and memory processes. We examined this with an fMRI study, in which participants passively listened to tonal series that had identical physical features and differed only in their regularity, as defined by the strength of transition structure between tones. We found that series-regularity induced systematic changes to global features of functional networks, including modularity strength, number of modules, partition structure, and degree distributions. In tandem, we used a novel node-level analysis to determine the extent to which brain regions maintained their within-module connectivity across experimental conditions. This analysis showed that primary sensory regions and those associated with default-mode processes are most likely to maintain their within-module connectivity across conditions, whereas prefrontal regions are least likely to do so. Our work documents a significant capacity for global-level brain network reorganization as a function of context. These findings suggest that modularity and other core, global features, while likely constrained by white-matter structural brain connections, are not completely determined by them. PMID:25988223

  10. Region-Specific Protein Abundance Changes in the Brain of MPTP-induced Parkinson’s Disease Mouse Model

    SciTech Connect

    Zhang, Xu; Zhou, Jianying; Chin, Mark H; Schepmoes, Athena A; Petyuk, Vladislav A; Weitz, Karl K; Petritis, Brianne O; Monroe, Matthew E; Camp, David G; Wood, Stephen A; Melega, William P; Bigelow, Diana J; Smith, Desmond J; Qian, Weijun; Smith, Richard D

    2010-02-15

    Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration in the nigrostriatal region of the brain; however, the neurodegeneration extends well beyond dopaminergic neurons. To gain a better understanding of the molecular changes relevant to PD, we applied two-dimensional LC-MS/MS to comparatively analyze the proteome changes in four brain regions (striatum, cerebellum, cortex, and the rest of brain) using a MPTP-induced PD mouse model with the objective to identify nigrostriatal-specific and other region-specific protein abundance changes. The combined analyses resulted in the identification of 4,895 non-redundant proteins with at least two unique peptides per protein. The relative abundance changes in each analyzed brain region were estimated based on the spectral count information. A total of 518 proteins were observed with significant MPTP-induced changes across different brain regions. 270 of these proteins were observed with specific changes occurring either only in the striatum and/or in the rest of the brain region that contains substantia nigra, suggesting that these proteins are associated with the underlying nigrostriatal pathways. Many of the proteins that exhibit significant abundance changes were associated with dopamine signaling, mitochondrial dysfunction, the ubiquitin system, calcium signaling, the oxidative stress response, and apoptosis. A set of proteins with either consistent change across all brain regions or with changes specific to the cortex and cerebellum regions were also detected. One of the interesting proteins is ubiquitin specific protease (USP9X), a deubiquination enzyme involved in the protection of proteins from degradation and promotion of the TGF-β pathway, which exhibited altered abundances in all brain regions. Western blot validation showed similar spatial changes, suggesting that USP9X is potentially associated with neurodegeneration. Together, this study for the first time presents an overall picture of proteome changes underlying both nigrostriatal pathways and other brain regions potentially involved in MPTP-induced neurodegeneration. The observed molecular changes provide a valuable reference resource for future hypothesis-driven functional studies of PD.

  11. Structural and functional neuroimaging studies of the suicidal brain.

    PubMed

    Desmyter, S; van Heeringen, C; Audenaert, K

    2011-06-01

    Suicidality is a major challenge for today's health care. Evidence suggests that there are differences in cognitive functioning of suicidal patients but the knowledge about the underlying neurobiology is limited. Brain imaging offers the advantage of a non-invasive in vivo direct estimation of detailed brain structure, regional brain functioning and estimation of molecular processes in the brain. We have reviewed the literature on neuroimaging studies of the suicidal brain. This article contains studies on structural imaging such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) and functional imaging, consisting of Positron Emission Tomography (PET), Single Photon Emission Tomography (SPECT) and functional MRI (fMRI). We classified the results of the different imaging modalities in structural and functional imaging. Within our research, we found no significant differences in the suicidal brain demonstrated by Computed Tomography. Magnetic Resonance Imaging studies in subjects with a history of suicide attempt on the other hand deliver differing results, mostly pointing at a higher prevalence of white (especially deep white matter and periventricular) and grey matter hyperintensities in the frontal, temporal and/or parietal lobe and decreased volumes in the frontal and temporal lobe. There seems to be a trend towards findings of reduced grey matter volume in the frontal lobe. Overall, there is no consensus of opinion on structural imaging of the suicidal brain. Research on functional imaging is further divided into studies in resting state, studies in activation conditions and studies on brain neurotransmitters, transporters and receptors. A common finding in functional neuroimaging in resting conditions is a decreased perfusion in the prefrontal cortex of suicidal patients. During cognitive activation, perfusion deficits in the prefrontal cortex have been observed. After fenfluramine challenge, the prefrontal cortex metabolism seems to be inversely correlated to the lethality of previous suicide attempt. The few studies that examined the serotonin transporter in suicide found no significant differences in binding potential. In suicide attempters there seems to be a negative correlation between impulsivity and SERT binding. Our group found a reduced 5-HT(2A) binding in the frontal cortex in patients with a recent suicide attempt. The binding index was significantly lower in the deliberate self injury patients compared to the deliberate self poisoning patients. The few authors that examined DAT binding in suicide found no significant DAT differences between patients and controls. However they demonstrated significant negative correlations between DAT binding potential and mental energy among suicide attempters, but not in healthy control subjects. We did not find studies measuring the binding potential of the noradrenalin or gamma amino butyric acid transporter or receptor in suicidal subjects. Several reports have suggested abnormalities of GABA neurotransmission in depression. During our literature search, we have focused on neuroimaging studies in suicidal populations, but in the absence of evidence in the literature on this group or when further collateral evidence is appropriate, this overview expands to results in impulsive aggressive or in depressed subjects. PMID:21216267

  12. Totally Tubular: The Mystery behind Function and Origin of the Brain Ventricular System

    PubMed Central

    Lowery, Laura Anne; Sive, Hazel

    2010-01-01

    Summary A unique feature of the vertebrate brain is the brain ventricular system, a series of connected cavities which are filled with cerebrospinal fluid (CSF) and surrounded by neuroepithelium. While CSF is critical for both adult brain function and embryonic brain development, neither development nor function of the brain ventricular system is fully understood. In this review, we discuss the mystery of why vertebrate brains have ventricles, and whence they originate. The brain ventricular system develops from the lumen of the neural tube, as the neuroepithelium undergoes morphogenesis. The molecular mechanisms underlying this ontogeny are described. We discuss possible functions of both adult and embryonic brain ventricles, as well as major brain defects that are associated with CSF and brain ventricular abnormalities. We conclude that vertebrates have taken advantage of their neural tube to form the essential brain ventricular system. PMID:19274662

  13. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    PubMed

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function. PMID:26041660

  14. Functional design specification: NASA form 1510

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The 1510 worksheet used to calculate approved facility project cost estimates is explained. Topics covered include data base considerations, program structure, relationship of the 1510 form to the 1509 form, and functions which the application must perform: WHATIF, TENENTER, TENTYPE, and data base utilities. A sample NASA form 1510 printout and a 1510 data dictionary are presented in the appendices along with the cost adjustment table, the floppy disk index, and methods for generating the calculated values (TENCALC) and for calculating cost adjustment (CONSTADJ). Storage requirements are given.

  15. Glycolysis-mediated control of blood-brain barrier development and function.

    PubMed

    Salmina, Alla B; Kuvacheva, Natalia V; Morgun, Andrey V; Komleva, Yulia K; Pozhilenkova, Elena A; Lopatina, Olga L; Gorina, Yana V; Taranushenko, Tatyana E; Petrova, Lyudmila L

    2015-07-01

    The blood-brain barrier (BBB) consists of differentiated cells integrating in one ensemble to control transport processes between the central nervous system (CNS) and peripheral blood. Molecular organization of BBB affects the extracellular content and cell metabolism in the CNS. Developmental aspects of BBB attract much attention in recent years, and barriergenesis is currently recognized as a very important and complex mechanism of CNS development and maturation. Metabolic control of angiogenesis/barriergenesis may be provided by glucose utilization within the neurovascular unit (NVU). The role of glycolysis in the brain has been reconsidered recently, and it is recognized now not only as a process active in hypoxic conditions, but also as a mechanism affecting signal transduction, synaptic activity, and brain development. There is growing evidence that glycolysis-derived metabolites, particularly, lactate, affect barriergenesis and functioning of BBB. In the brain, lactate produced in astrocytes or endothelial cells can be transported to the extracellular space via monocarboxylate transporters (MCTs), and may act on the adjoining cells via specific lactate receptors. Astrocytes are one of the major sources of lactate production in the brain and significantly contribute to the regulation of BBB development and functioning. Active glycolysis in astrocytes is required for effective support of neuronal activity and angiogenesis, while endothelial cells regulate bioavailability of lactate for brain cells adjusting its bidirectional transport through the BBB. In this article, we review the current knowledge with regard to energy production in endothelial and astroglial cells within the NVU. In addition, we describe lactate-driven mechanisms and action of alternative products of glucose metabolism affecting BBB structural and functional integrity in developing and mature brain. PMID:25900038

  16. Brain Oscillations and Functional Connectivity during Overt Language Production

    PubMed Central

    Ewald, Arne; Aristei, Sabrina; Nolte, Guido; Rahman, Rasha Abdel

    2012-01-01

    In the present study we investigate the communication of different large scale brain sites during an overt language production task with state of the art methods for the estimation of EEG functional connectivity. Participants performed a semantic blocking task in which objects were named in semantically homogeneous blocks of trials consisting of members of a semantic category (e.g., all objects are tools) or in heterogeneous blocks, consisting of unrelated objects. The classic pattern of slower naming times in the homogeneous relative to heterogeneous blocks is assumed to reflect the duration of lexical selection. For the collected data in the homogeneous and heterogeneous conditions the imaginary part of coherency (ImC) was evaluated at different frequencies. The ImC is a measure for detecting the coupling of different brain sites acting on sensor level. Most importantly, the ImC is robust to the artifact of volume conduction. We analyzed the ImC at all pairs of 56 EEG channels across all frequencies. Contrasting the two experimental conditions we found pronounced differences in the theta band at 7 Hz and estimated the most dominant underlying brain sources via a minimum norm inverse solution based on the ImC. As a result of the source localization, we observed connectivity between occipito-temporal and frontal areas, which are well-known to play a major role in lexical-semantic language processes. Our findings demonstrate the feasibility of investigating interactive brain activity during overt language production. PMID:22701106

  17. Functional magnetic resonance imaging reflects changes in brain functioning with sedation.

    PubMed

    Starbuck, Victoria N; Kay, Gary G; Platenberg, R. Craig; Lin, Chin-Shoou; Zielinski, Brandon A

    2000-12-01

    Functional magnetic resonance imaging (fMRI) studies have demonstrated localized brain activation during cognitive tasks. Brain activation increases with task complexity and decreases with familiarity. This study investigates how sleepiness alters the relationship between brain activation and task familiarity. We hypothesize that sleepiness prevents the reduction in activation associated with practice. Twenty-nine individuals rated their sleepiness using the Stanford Sleepiness Scale before fMRI. During imaging, subjects performed the Paced Auditory Serial Addition Test, a continuous mental arithmetic task. A positive correlation was observed between self-rated sleepiness and frontal brain activation. Fourteen subjects participated in phase 2. Sleepiness was induced by evening dosing with chlorpheniramine (CP) (8 mg or 12 mg) and terfenadine (60 mg) in the morning for 3 days before the second fMRI scan. The Multiple Sleep Latency Test (MSLT) was also performed. Results revealed a significant increase in fMRI activation in proportion to the dose of CP. In contrast, for all subjects receiving placebo there was a reduction in brain activation. MSLT revealed significant daytime sleepiness for subjects receiving CP. These findings suggest that sleepiness interferes with efficiency of brain functioning. The sleepy or sedated brain shows increased oxygen utilization during performance of a familiar cognitive task. Thus, the beneficial effect of prior task exposure is lost under conditions of sedation. Copyright 2000 John Wiley & Sons, Ltd. PMID:12404614

  18. A Mapping Between Structural and Functional Brain Networks.

    PubMed

    Meier, Jil; Tewarie, Prejaas; Hillebrand, Arjan; Douw, Linda; van Dijk, Bob W; Stufflebeam, Steven M; Van Mieghem, Piet

    2016-05-01

    The relationship between structural and functional brain networks is still highly debated. Most previous studies have used a single functional imaging modality to analyze this relationship. In this work, we use multimodal data, from functional MRI, magnetoencephalography, and diffusion tensor imaging, and assume that there exists a mapping between the connectivity matrices of the resting-state functional and structural networks. We investigate this mapping employing group averaged as well as individual data. We indeed find a significantly high goodness of fit level for this structure-function mapping. Our analysis suggests that a functional connection is shaped by all walks up to the diameter in the structural network in both modality cases. When analyzing the inverse mapping, from function to structure, longer walks in the functional network also seem to possess minor influence on the structural connection strengths. Even though similar overall properties for the structure-function mapping are found for different functional modalities, our results indicate that the structure-function relationship is modality dependent. PMID:26860437

  19. Functional magnetic resonance imaging of the brain: a quick review.

    PubMed

    Vaghela, Viratsinh; Kesavadas, Chandrasekharan; Thomas, Bejoy

    2010-01-01

    Ability to non-invasively map the hemodynamic changes occurring focally in areas of brain involved in various motor, sensory and cognitive functions by functional magnetic resonance imaging (fMRI) has revolutionized research in neuroscience in the last two decades. This technique has already gained clinical use especially in pre-surgical evaluation of epilepsy and neurosurgical planning of resection of mass lesions adjacent to eloquent cortex. In this review we attempt to illustrate basic principles and techniques of fMRI, its applications, practical points to consider while performing and evaluating clinical fMRI and its limitations. PMID:21150054

  20. Disrupted resting-state functional architecture of the brain after 45-day simulated microgravity

    PubMed Central

    Zhou, Yuan; Wang, Yun; Rao, Li-Lin; Liang, Zhu-Yuan; Chen, Xiao-Ping; Zheng, Dang; Tan, Cheng; Tian, Zhi-Qiang; Wang, Chun-Hui; Bai, Yan-Qiang; Chen, Shan-Guang; Li, Shu

    2014-01-01

    Long-term spaceflight induces both physiological and psychological changes in astronauts. To understand the neural mechanisms underlying these physiological and psychological changes, it is critical to investigate the effects of microgravity on the functional architecture of the brain. In this study, we used resting-state functional MRI (rs-fMRI) to study whether the functional architecture of the brain is altered after 45 days of −6° head-down tilt (HDT) bed rest, which is a reliable model for the simulation of microgravity. Sixteen healthy male volunteers underwent rs-fMRI scans before and after 45 days of −6° HDT bed rest. Specifically, we used a commonly employed graph-based measure of network organization, i.e., degree centrality (DC), to perform a full-brain exploration of the regions that were influenced by simulated microgravity. We subsequently examined the functional connectivities of these regions using a seed-based resting-state functional connectivity (RSFC) analysis. We found decreased DC in two regions, the left anterior insula (aINS) and the anterior part of the middle cingulate cortex (MCC; also called the dorsal anterior cingulate cortex in many studies), in the male volunteers after 45 days of −6° HDT bed rest. Furthermore, seed-based RSFC analyses revealed that a functional network anchored in the aINS and MCC was particularly influenced by simulated microgravity. These results provide evidence that simulated microgravity alters the resting-state functional architecture of the brains of males and suggest that the processing of salience information, which is primarily subserved by the aINS–MCC functional network, is particularly influenced by spaceflight. The current findings provide a new perspective for understanding the relationships between microgravity, cognitive function, autonomic neural function, and central neural activity. PMID:24926242

  1. Altered functional brain networks in Prader-Willi syndrome.

    PubMed

    Zhang, Yi; Zhao, Heng; Qiu, Siyou; Tian, Jie; Wen, Xiaotong; Miller, Jennifer L; von Deneen, Karen M; Zhou, Zhenyu; Gold, Mark S; Liu, Yijun

    2013-06-01

    Prader-Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating-related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting-state functional MRI techniques to investigate abnormal brain networks related to eating disorders in children with PWS. First, we applied amplitude of low-frequency fluctuation analysis to define the regions of interest that showed significant alterations in resting-state brain activity levels in patients compared with their sibling control group. We then applied a functional connectivity (FC) analysis to these regions of interest in order to characterize interactions among the brain regions. Our results demonstrated that patients with PWS showed decreased FC strength in the medial prefrontal cortex (MPFC)/inferior parietal lobe (IPL), MPFC/precuneus, IPL/precuneus and IPL/hippocampus in the default mode network; decreased FC strength in the pre-/postcentral gyri and dorsolateral prefrontal cortex (DLPFC)/orbitofrontal cortex (OFC) in the motor sensory network and prefrontal cortex network, respectively; and increased FC strength in the anterior cingulate cortex/insula, ventrolateral prefrontal cortex (VLPFC)/OFC and DLPFC/VLPFC in the core network and prefrontal cortex network, respectively. These findings indicate that there are FC alterations among the brain regions implicated in eating as well as rewarding, even during the resting state, which may provide further evidence supporting the use of PWS as a model to study obesity and to provide information on potential neural targets for the medical treatment of overeating. PMID:23335390

  2. Altered functional brain networks in Prader–Willi syndrome

    PubMed Central

    Zhang, Yi; Zhao, Heng; Qiu, Siyou; Tian, Jie; Wen, Xiaotong; Miller, Jennifer L.; von Deneen, Karen M.; Zhou, Zhenyu; Gold, Mark S.; Liu, Yijun

    2013-01-01

    Prader–Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating-related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting-state functional MRI techniques to investigate abnormal brain networks related to eating disorders in children with PWS. First, we applied amplitude of low-frequency fluctuation analysis to define the regions of interest that showed significant alterations in resting-state brain activity levels in patients compared with their sibling control group. We then applied a functional connectivity (FC) analysis to these regions of interest in order to characterize interactions among the brain regions. Our results demonstrated that patients with PWS showed decreased FC strength in the medial prefrontal cortex (MPFC)/inferior parietal lobe (IPL), MPFC/precuneus, IPL/precuneus and IPL/hippocampus in the default mode network; decreased FC strength in the pre-/postcentral gyri and dorsolateral prefrontal cortex (DLPFC)/orbitofrontal cortex (OFC) in the motor sensory network and prefrontal cortex network, respectively; and increased FC strength in the anterior cingulate cortex/insula, ventrolateral prefrontal cortex (VLPFC)/OFC and DLPFC/VLPFC in the core network and prefrontal cortex network, respectively. These findings indicate that there are FC alterations among the brain regions implicated in eating as well as rewarding, even during the resting state, which may provide further evidence supporting the use of PWS as a model to study obesity and to provide information on potential neural targets for the medical treatment of overeating. PMID:23335390

  3. Neuroplasticity as a function of second language learning: anatomical changes in the human brain.

    PubMed

    Li, Ping; Legault, Jennifer; Litcofsky, Kaitlyn A

    2014-09-01

    The brain has an extraordinary ability to functionally and physically change or reconfigure its structure in response to environmental stimulus, cognitive demand, or behavioral experience. This property, known as neuroplasticity, has been examined extensively in many domains. But how does neuroplasticity occur in the brain as a function of an individual's experience with a second language? It is not until recently that we have gained some understanding of this question by examining the anatomical changes as well as functional neural patterns that are induced by the learning and use of multiple languages. In this article we review emerging evidence regarding how structural neuroplasticity occurs in the brain as a result of one's bilingual experience. Our review aims at identifying the processes and mechanisms that drive experience-dependent anatomical changes, and integrating structural imaging evidence with current knowledge of functional neural plasticity of language and other cognitive skills. The evidence reviewed so far portrays a picture that is highly consistent with structural neuroplasticity observed for other domains: second language experience-induced brain changes, including increased gray matter (GM) density and white matter (WM) integrity, can be found in children, young adults, and the elderly; can occur rapidly with short-term language learning or training; and are sensitive to age, age of acquisition, proficiency or performance level, language-specific characteristics, and individual differences. We conclude with a theoretical perspective on neuroplasticity in language and bilingualism, and point to future directions for research. PMID:24996640

  4. Model-free functional MRI analysis for detecting low-frequency functional connectivity in the human brain

    NASA Astrophysics Data System (ADS)

    Wismueller, Axel; Lange, Oliver; Auer, Dorothee; Leinsinger, Gerda

    2010-03-01

    Slowly varying temporally correlated activity fluctuations between functionally related brain areas have been identified by functional magnetic resonance imaging (fMRI) research in recent years. These low-frequency oscillations of less than 0.08 Hz appear to play a major role in various dynamic functional brain networks, such as the so-called 'default mode' network. They also have been observed as a property of symmetric cortices, and they are known to be present in the motor cortex among others. These low-frequency data are difficult to detect and quantify in fMRI. Traditionally, user-based regions of interests (ROI) or 'seed clusters' have been the primary analysis method. In this paper, we propose unsupervised clustering algorithms based on various distance measures to detect functional connectivity in resting state fMRI. The achieved results are evaluated quantitatively for different distance measures. The Euclidian metric implemented by standard unsupervised clustering approaches is compared with a non-metric topographic mapping of proximities based on the the mutual prediction error between pixel-specific signal dynamics time-series. It is shown that functional connectivity in the motor cortex of the human brain can be detected based on such model-free analysis methods for resting state fMRI.

  5. Hypothalamic-Pituitary Function in Brain Death: A Review.

    PubMed

    Nair-Collins, Michael; Northrup, Jesse; Olcese, James

    2016-01-01

    The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord. PMID:24692211

  6. A Multivariate Granger Causality Concept towards Full Brain Functional Connectivity

    PubMed Central

    Schmid-Hertel, Nicole; Witte, Herbert; Wismüller, Axel; Leistritz, Lutz

    2016-01-01

    Detecting changes of spatially high-resolution functional connectivity patterns in the brain is crucial for improving the fundamental understanding of brain function in both health and disease, yet still poses one of the biggest challenges in computational neuroscience. Currently, classical multivariate Granger Causality analyses of directed interactions between single process components in coupled systems are commonly restricted to spatially low- dimensional data, which requires a pre-selection or aggregation of time series as a preprocessing step. In this paper we propose a new fully multivariate Granger Causality approach with embedded dimension reduction that makes it possible to obtain a representation of functional connectivity for spatially high-dimensional data. The resulting functional connectivity networks may consist of several thousand vertices and thus contain more detailed information compared to connectivity networks obtained from approaches based on particular regions of interest. Our large scale Granger Causality approach is applied to synthetic and resting state fMRI data with a focus on how well network community structure, which represents a functional segmentation of the network, is preserved. It is demonstrated that a number of different community detection algorithms, which utilize a variety of algorithmic strategies and exploit topological features differently, reveal meaningful information on the underlying network module structure. PMID:27064897

  7. Reactivation of Context-Specific Brain Regions during Retrieval

    ERIC Educational Resources Information Center

    Skinner, Erin I.; Grady, Cheryl L.; Fernandes, Myra A.

    2010-01-01

    The neural correlates of recollection were examined using event-related functional MRI. We examined how the presence of different visual context information during encoding of target words influenced later recollection for the words presented alone at retrieval. Participants studied words presented with different pictures of faces or scrambled…

  8. Dietary essential fatty acids and brain function: a developmental perspective on mechanisms.

    PubMed

    Wainwright, Patricia E

    2002-02-01

    Brain development is a complex interactive process in which early disruptive events can have long-lasting effects on later functional adaptation. It is a process that is dependent on the timely orchestration of external and internal inputs through sophisticated intra- and intercellular signalling pathways. Long-chain polyunsaturated fatty acids (LCPUFA), specifically arachidonic acid and docosahexaenoic acid (DHA), accrue rapidly in the grey matter of the brain during development, and brain fatty acid (FA) composition reflects dietary availability. Membrane lipid components can influence signal transduction cascades in various ways, which in the case of LCPUFA include the important regulatory functions mediated by the eicosanoids, and extend to long-term regulation through effects on gene transcription. Our work indicates that FA imbalance as well as specific FA deficiencies can affect development adversely, including the ability to respond to environmental stimulation. For example, although the impaired water-maze performance of mice fed a saturated-fat diet improved in response to early environmental enrichment, the brains of these animals showed less complex patterns of dendritic branching. Dietary n-3 FA deficiency influences specific neurotransmitter systems, particularly the dopamine systems of the frontal cortex. We showed that dietary deficiency of n-3 FA impaired the performance of rats on delayed matching-to-place in the water maze, a task of the type associated with prefrontal dopamine function. We did not, however, find an association over a wider range of brain DHA levels and performance on this task. Some, but not all, studies of human infants suggest that dietary DHA may play a role in cognitive development as well as in some neurodevelopmental disorders; this possibility has important implications for population health. PMID:12002796

  9. Identifying functional subdivisions in the human brain using meta-analytic activation modeling-based parcellation.

    PubMed

    Yang, Yong; Fan, Lingzhong; Chu, Congying; Zhuo, Junjie; Wang, Jiaojian; Fox, Peter T; Eickhoff, Simon B; Jiang, Tianzi

    2016-01-01

    Parcellation of the human brain into fine-grained units by grouping voxels into distinct clusters has been an effective approach for delineating specific brain regions and their subregions. Published neuroimaging studies employing coordinate-based meta-analyses have shown that the activation foci and their corresponding behavioral categories may contain useful information about the anatomical-functional organization of brain regions. Inspired by these developments, we proposed a new parcellation scheme called meta-analytic activation modeling-based parcellation (MAMP) that uses meta-analytically obtained information. The raw meta data, including the experiments and the reported activation coordinates related to a brain region of interest, were acquired from the Brainmap database. Using this data, we first obtained the "modeled activation" pattern by modeling the voxel-wise activation probability given spatial uncertainty for each experiment that featured at least one focus within the region of interest. Then, we processed these "modeled activation" patterns across the experiments with a K-means clustering algorithm to group the voxels into different subregions. In order to verify the reliability of the method, we employed our method to parcellate the amygdala and the left Brodmann area 44 (BA44). The parcellation results were quite consistent with previous cytoarchitectonic and in vivo neuroimaging findings. Therefore, the MAMP proposed in the current study could be a useful complement to other methods for uncovering the functional organization of the human brain. PMID:26296500

  10. On the effects of testosterone on brain behavioral functions

    PubMed Central

    Celec, Peter; Ostatníková, Daniela; Hodosy, Július

    2015-01-01

    Testosterone influences the brain via organizational and activational effects. Numerous relevant studies on rodents and a few on humans focusing on specific behavioral and cognitive parameters have been published. The results are, unfortunately, controversial and puzzling. Dosing, timing, even the application route seem to considerably affect the outcomes. In addition, the methods used for the assessment of psychometric parameters are a bit less than ideal regarding their validity and reproducibility. Metabolism of testosterone contributes to the complexity of its actions. Reduction to dihydrotestosterone by 5-alpha reductase increases the androgen activity; conversion to estradiol by aromatase converts the androgen to estrogen activity. Recently, the non-genomic effects of testosterone on behavior bypassing the nuclear receptors have attracted the interest of researchers. This review tries to summarize the current understanding of the complexity of the effects of testosterone on brain with special focus on their role in the known sex differences. PMID:25741229

  11. Genetic and Environmental Contributions to Functional Connectivity Architecture of the Human Brain.

    PubMed

    Yang, Zhi; Zuo, Xi-Nian; McMahon, Katie L; Craddock, R Cameron; Kelly, Clare; de Zubicaray, Greig I; Hickie, Ian; Bandettini, Peter A; Castellanos, F Xavier; Milham, Michael P; Wright, Margaret J

    2016-05-01

    One of the grand challenges faced by neuroscience is to delineate the determinants of interindividual variation in the comprehensive structural and functional connection matrices that comprise the human connectome. At present, this endeavor appears most tractable at the macroanatomic scale, where intrinsic brain activity exhibits robust patterns of synchrony that recapitulate core functional circuits at the individual level. Here, we use a classical twin study design to examine the heritability of intrinsic functional network properties in 101 twin pairs, including network activity (i.e., variance of a network's specific temporal fluctuations) and internetwork coherence (i.e., correlation between networks' specific temporal fluctuations). Five of 7 networks exhibited significantly heritable (23.3-65.2%) network activity, 6 of the 21 internetwork coherences were significantly heritable (25.6-42.0%), and 11 of the 21 internetwork coherences were significantly influenced by common environmental factors (18.0-47.1%). These results suggest that the source of interindividual variation in functional connectome has a modular architecture: individual modules represented by intrinsic connectivity networks are genetic controlled, while environmental factors influence the interplays between the modules. This work further provides network-specific hypotheses for discovery of the specific genetic and environmental factors influencing functional specialization and integration of the human brain. PMID:26891986

  12. Genetic and Environmental Contributions to Functional Connectivity Architecture of the Human Brain

    PubMed Central

    Yang, Zhi; Zuo, Xi-Nian; McMahon, Katie L.; Craddock, R. Cameron; Kelly, Clare; de Zubicaray, Greig I.; Hickie, Ian; Bandettini, Peter A.; Castellanos, F. Xavier; Milham, Michael P.; Wright, Margaret J.

    2016-01-01

    One of the grand challenges faced by neuroscience is to delineate the determinants of interindividual variation in the comprehensive structural and functional connection matrices that comprise the human connectome. At present, this endeavor appears most tractable at the macroanatomic scale, where intrinsic brain activity exhibits robust patterns of synchrony that recapitulate core functional circuits at the individual level. Here, we use a classical twin study design to examine the heritability of intrinsic functional network properties in 101 twin pairs, including network activity (i.e., variance of a network's specific temporal fluctuations) and internetwork coherence (i.e., correlation between networks' specific temporal fluctuations). Five of 7 networks exhibited significantly heritable (23.3–65.2%) network activity, 6 of the 21 internetwork coherences were significantly heritable (25.6–42.0%), and 11 of the 21 internetwork coherences were significantly influenced by common environmental factors (18.0–47.1%). These results suggest that the source of interindividual variation in functional connectome has a modular architecture: individual modules represented by intrinsic connectivity networks are genetic controlled, while environmental factors influence the interplays between the modules. This work further provides network-specific hypotheses for discovery of the specific genetic and environmental factors influencing functional specialization and integration of the human brain. PMID:26891986

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

    PubMed Central

    Bock, Jrg; Riedel, Anett; Braun, Katharina

    2012-01-01

    The trumpet-tailed rat or degu (Octodon degus) is an established model to investigate the consequences of early stress on the development of emotional brain circuits and behavior. The aim of this study was to identify brain circuits, that respond to different stress conditions and to test if acute stress alters functional coupling of brain activity among prefrontal and limbic regions. Using functional imaging (2-Fluoro-deoxyglucose method) in 8-day-old male degu pups the following stress conditions were compared: (A) pups together with parents and siblings (control), (B) separation of the litter from the parents, (C) individual separation from parents and siblings, and (D) individual separation and presentation of maternal calls. Condition (B) significantly downregulated brain activity in the prefrontal cortex, hippocampus, nucleus accumbens (NAcc), and sensory areas compared to controls. Activity decrease was even more pronounced during condition (C), where, in contrast to all other regions, activity in the PAG was increased. Interestingly, brain activity in stress-associated brain regions such as the amygdala and habenula was not affected. In condition (D) maternal vocalizations reactivated brain activity in the cingulate and precentral medial cortex, NAcc, and striatum and in sensory areas. In contrast, reduced activity was measured in the prelimbic and infralimbic cortex (IL) and in the hippocampus and amygdala. Correlation analysis revealed complex, region- and situation-specific changes of interregional functional coupling among prefrontal and limbic brain regions during stress exposure. We show here for the first time that early life stress results in a widespread reduction of brain activity in the infant brain and changes interregional functional coupling. Moreover, maternal vocalizations can partly buffer stress-induced decrease in brain activity in some regions and evoked very different functional coupling patterns compared to the three other conditions. PMID:22590453

  14. Modularity and Self-Organized Functional Architectures in the Brain

    NASA Astrophysics Data System (ADS)

    Iyer, Laxmi; Minai, Ali A.; Doboli, Simona; Brown, Vincent R.

    It is generally believed that cognition involves the self-organization of coherent dy- namic functional networks across several brain regions in response to incoming stimulus and internal modulation. These context-dependent networks arise continually from the spatiotemporally multi-scale structural substrate of the brain configured by evolution, development and previous experience, persisting for 100-200 ms and generating re- sponses such as imagery, recall and motor action. In the current paper, we show that a system of interacting modular attractor networks can use a selective mechanism for assembling functional networks from the modular substrate. We use the approach to develop a model of idea-generation in the brain. Ideas are modeled as combinations of concepts organized in a recurrent network that reflects previous associations between them. The dynamics of this network, resulting in the transient co-activation of concept groups, is seen as a search through the space of ideas, and attractor dynamics is used to "shape" this search. The process is required to encompass both rapid retrieval of old ideas in familiar contexts and efficient search for novel ones in unfamiliar situations (or during brainstorming). The inclusion of an adaptive modulatory mechanism allows the network to balance the competing requirements of exploiting previous learning and exploring new possibilities as needed in different contexts.

  15. Heritability of human brain functioning as assessed by electroencephalography

    SciTech Connect

    Beijsterveldt, C.E.M. van; Geus, E.J.C. de; Boomsma, D.I.

    1996-03-01

    To study the genetic and environmental contributions to individual differences in CNS functioning, the electroencephalogram (EEG) was measured in 213 twin pairs age 16 years. EEG was measured in 91 MZ and 122 DZ twins. To quantify sex differences in the genetic architecture, EEG was measured in female and male same-sex twins and in opposite-sex twins. EEG was recorded on 14 scalp positions during quiet resting with eyes closed. Spectral powers were calculated for four frequency bands: delta, theta, alpha, and beta. Twin correlations pointed toward high genetic influences for all these powers and scalp locations. Model fitting confirmed these findings; the largest part of the variance of the EEG is explained by additive genetic factors. The averaged heritabilities for the delta, theta, alpha, and beta frequencies was 76%, 89%, 89%, and 86%, respectively. Multivariate analyses suggested that the same genes for EEG alpha rhythm were expressed in different brain areas in the left and right hemisphere. This study shows that brain functioning, as indexed by rhythmic brain-electrical activity, is one of the most heritable characteristics in humans. 44 refs., 5 figs., 4 tabs.

  16. Socioeconomic status and functional brain development - associations in early infancy.

    PubMed

    Tomalski, Przemyslaw; Moore, Derek G; Ribeiro, Helena; Axelsson, Emma L; Murphy, Elizabeth; Karmiloff-Smith, Annette; Johnson, Mark H; Kushnerenko, Elena

    2013-09-01

    Socioeconomic status (SES) impacts on both structural and functional brain development in childhood, but how early its effects can be demonstrated is unknown. In this study we measured resting baseline EEG activity in the gamma frequency range in awake 6-9-month-olds from areas of East London with high socioeconomic deprivation. Between-subject comparisons of infants from low- and high-income families revealed significantly lower frontal gamma power in infants from low-income homes. Similar power differences were found when comparing infants according to maternal occupation, with lower occupational status groups yielding lower power. Infant sleep, maternal education, length of gestation, and birth weight, as well as smoke exposure and bilingualism, did not explain these differences. Our results show that the effects of socioeconomic disparities on brain activity can already be detected in early infancy, potentially pointing to very early risk for language and attention difficulties. This is the first study to reveal region-selective differences in functional brain development associated with early infancy in low-income families. PMID:24033573

  17. Roles of Brain Angiotensin II in Cognitive Function and Dementia

    PubMed Central

    Mogi, Masaki; Iwanami, Jun; Horiuchi, Masatsugu

    2012-01-01

    The brain renin-angiotensin system (RAS) has been highlighted as having a pathological role in stroke, dementia, and neurodegenerative disease. Particularly, in dementia, epidemiological studies indicate a preventive effect of RAS blockade on cognitive impairment in Alzheimer disease (AD). Moreover, basic experiments suggest a role of brain angiotensin II in neural injury, neuroinflammation, and cognitive function and that RAS blockade attenuates cognitive impairment in rodent dementia models of AD. Therefore, RAS regulation is expected to have therapeutic potential for AD. Here, we discuss the role of angiotensin II in cognitive impairment and AD. Angiotensin II binds to the type 2 receptor (AT2) and works mainly by binding with the type 1 receptor (AT1). AT2 receptor signaling plays a role in protection against multiple-organ damage. A direct AT2 receptor agonist is now available and is expected to reduce inflammation and oxidative stress and enhance cell differentiation. We and other groups reported that AT2 receptor activation enhances neuronal differentiation and neurite outgrowth in the brain. Here, we also review the effect of the AT2 receptor on cognitive function. RAS modulation may be a new therapeutic option for dementia including AD in the future. PMID:23304450

  18. kappa-Opioid receptor signaling and brain reward function.

    PubMed

    Bruijnzeel, Adrie W

    2009-12-11

    The dynorphin-like peptides have profound effects on the state of the brain reward system and human and animal behavior. The dynorphin-like peptides affect locomotor activity, food intake, sexual behavior, anxiety-like behavior, and drug intake. Stimulation of kappa-opioid receptors, the endogenous receptor for the dynorphin-like peptides, inhibits dopamine release in the striatum (nucleus accumbens and caudate putamen) and induces a negative mood state in humans and animals. The administration of drugs of abuse increases the release of dopamine in the striatum and mediates the concomitant release of dynorphin-like peptides in this brain region. The reviewed studies suggest that chronic drug intake leads to an upregulation of the brain dynorphin system in the striatum and in particular in the dorsal part of the striatum/caudate putamen. This might inhibit drug-induced dopamine release and provide protection against the neurotoxic effects of high dopamine levels. After the discontinuation of chronic drug intake these neuroadaptations remain unopposed which has been suggested to contribute to the negative emotional state associated with drug withdrawal and increased drug intake. kappa-Opioid receptor agonists have also been shown to inhibit calcium channels. Calcium channel inhibitors have antidepressant-like effects and inhibit the release of norepinephrine. This might explain that in some studies kappa-opioid receptor agonists attenuate nicotine and opioid withdrawal symptomatology. A better understanding of the role of dynorphins in the regulation of brain reward function might contribute to the development of novel treatments for mood disorders and other disorders that stem from a dysregulation of the brain reward system. PMID:19804796

  19. Kappa-opioid receptor signaling and brain reward function

    PubMed Central

    Bruijnzeel, Adrie W.

    2009-01-01

    The dynorphin-like peptides have profound effects on the state of the brain reward system and human and animal behavior. The dynorphin-like peptides affect locomotor activity, food intake, sexual behavior, anxiety-like behavior, and drug intake. Stimulation of kappa-opioid receptors, the endogenous receptor for the dynorphin-like peptides, inhibits dopamine release in the striatum (nucleus accumbens and caudate putamen) and induces a negative mood state in humans and animals. The administration of drugs of abuse increases the release of dopamine in the striatum and mediates the concomitant release of dynorphin-like peptides in this brain region. The reviewed studies suggest that chronic drug intake leads to an upregulation of the brain dynorphin system in the striatum and in particular in the dorsal part of the striatum/caudate putamen. This might inhibit drug-induced dopamine release and provide protection against the neurotoxic effects of high dopamine levels. After the discontinuation of chronic drug intake these neuroadaptations remain unopposed which has been suggested to contribute to the negative emotional state associated with drug withdrawal and increased drug intake. Kappa-opioid receptor agonists have also been shown to inhibit calcium channels. Calcium channel inhibitors have antidepressant-like effects and inhibit the release of norepinephrine. This might explain that in some studies kappa-opioid receptor agonists attenuate nicotine and opioid withdrawal symptomatology. A better understanding of the role of dynorphins in the regulation of brain reward function might contribute to the development of novel treatments for mood disorders and other disorders that stem from a dysregulation of the brain reward system. PMID:19804796

  20. Structural and Functional Rich Club Organization of the Brain in Children and Adults

    PubMed Central

    Grayson, David S.; Ray, Siddharth; Carpenter, Samuel; Iyer, Swathi; Dias, Taciana G. Costa; Stevens, Corinne; Nigg, Joel T.; Fair, Damien A.

    2014-01-01

    Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain’s white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain’s major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism. PMID:24505468

  1. STRENGTHENED FUNCTIONAL CONNECTIVITY IN THE BRAIN DURING MUSCLE FATIGUE

    PubMed Central

    Jiang, Zhiguo; Wang, Xiao-Feng; Kisiel-Sajewicz, Katarzyna; Yan, Jin H; Yue, Guang H

    2012-01-01

    Fatigue caused by sustaining submaximal-intensity muscle contraction(s) involves increased activation in the brain such as primary motor cortex (M1), primary sensory cortex (S1), Premotor and supplementary motor area (PM&SMA) and prefrontal cortex (PFC). The synchronized increases in activation level in these cortical areas suggest fatigue-related strengthening of functional coupling within the motor control network. In the present study, this hypothesis was tested using the cross-correlation based functional connectivity (FC) analysis method. Ten subjects performed a 20-minute intermittent (3.5s ON/6.5s OFF, 120 trials total) handgrip task using the right hand at 50% maximal voluntary contraction (MVC) force level while their brain was scanned by a 3T Siemens Trio scanner using echo planar imaging (EPI) sequence. A representative signal time course of the left M1 was extracted by averaging the time course data of a 2-mm cluster of neighboring voxels of local maximal activation foci, which was identified by a general linear model. Two FC activation maps were created for each subject by cross-correlating the time course data of the minimal (the first 10 trials) and significant (the last 10 trials) fatigue stages across all the voxels in the brain to the corresponding representative time course. Histogram and quantile regression analysis were used to compare the FC between the minimal and significant fatigue stages and the results showed a significant increase in FC among multiple cortical regions, including right M1 and bilateral PM&SMA, S1 and PFC. This strengthened FC indicates that when muscle fatigue worsens, many brain regions increase their coupling with the left M1, the primary motor output control center for the right handgrip, to compensate for diminished force generating capability of the muscle in a coordinated fashion by enhancing the descending command for greater muscle recruitment to maintain the same force. PMID:22197785

  2. PROTEIN III, A NEURON-SPECIFIC PHOSPHOPROTEIN: VARIANT FORMS FOUND IN HUMAN BRAIN

    EPA Science Inventory

    Recent work in the laboratory has shown the presence of many neuron-specific phosphoproteins in the mammalian nervous system. Two of these proteins, Protein III and Synapsin I, are specifically associated with synaptic vesicles in neurons throughout the brain. Protein III consist...

  3. Sleep-disordered breathing: effects on brain structure and function

    PubMed Central

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

    2013-01-01

    Sleep-disordered breathing is accompanied by neural injury that affects a wide range of physiological systems which include processes for sensing chemoreception and airflow, driving respiratory musculature, timing circuitry for coordination of breathing patterning, and integration of blood pressure mechanisms with respiration. The damage also occurs in regions mediating emotion and mood, as well as areas regulating memory and cognitive functioning, and appears in structures that serve significant glycemic control processes. The injured structures include brain areas involved in hormone release and action of major neurotransmitters, including those playing a role in depression. The injury is reflected in a range of structural magnetic resonance procedures, and also appears as functional distortions of evoked activity in brain areas mediating vital autonomic and breathing functions. The damage is preferentially unilateral, and includes axonal projections; the asymmetry of the injury poses unique concerns for sympathetic discharge and potential consequences for arrhythmia. Sleep-disordered breathing should be viewed as a condition that includes central nervous system injury and impaired function; the processes underlying injury remain unclear. PMID:23643610

  4. Functional interactions between intrinsic brain activity and behavior.

    PubMed

    Sadaghiani, Sepideh; Kleinschmidt, Andreas

    2013-10-15

    The brain continuously maintains a remarkably high level of intrinsic activity. This activity is non-stationary and its dynamics reveal highly structured patterns across several spatial scales, from fine-grained functional architecture in sensory cortices to large-scale networks. The mechanistic function of this activity is only poorly understood. The central goal of the current review is to provide an integrated summary of recent studies on structure, dynamics and behavioral consequences of spontaneous brain activity. In light of these empirical observations we propose that the structure of ongoing activity and its itinerant nature can be understood as an indispensible memory system modeling the statistical structure of the world. We review the dynamic properties of ongoing activity, and how they are malleable over short to long temporal scales that permit adapting over a range of short- to long-term cognitive challenges. We conclude by reviewing how the functional significance of ongoing activity manifests in its impact on human action, perception, and higher cognitive function. PMID:23643921

  5. Reorganization of Functional Connectivity as a Correlate of Cognitive Recovery in Acquired Brain Injury

    ERIC Educational Resources Information Center

    Castellanos, Nazareth P.; Paul, Nuria; Ordonez, Victoria E.; Demuynck, Olivier; Bajo, Ricardo; Campo, Pablo; Bilbao, Alvaro; Ortiz, Tomas; del-Pozo, Francisco; Maestu, Fernando

    2010-01-01

    Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on…

  6. Reorganization of Functional Connectivity as a Correlate of Cognitive Recovery in Acquired Brain Injury

    ERIC Educational Resources Information Center

    Castellanos, Nazareth P.; Paul, Nuria; Ordonez, Victoria E.; Demuynck, Olivier; Bajo, Ricardo; Campo, Pablo; Bilbao, Alvaro; Ortiz, Tomas; del-Pozo, Francisco; Maestu, Fernando

    2010-01-01

    Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on

  7. Brain region-specific altered expression and association of mitochondria-related genes in autism

    PubMed Central

    2012-01-01

    Background Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions. Methods For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct (∆∆Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism. Results Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients. Conclusions Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted. PMID:23116158

  8. Rewiring the Brain: Potential Role of the Premotor Cortex in Motor Control, Learning, and Recovery of Function Following Brain Injury

    PubMed Central

    Kantak, Shailesh S.; Stinear, James W.; Buch, Ethan R.; Cohen, Leonardo G.

    2016-01-01

    The brain is a plastic organ with a capability to reorganize in response to behavior and/or injury. Following injury to the motor cortex or emergent corticospinal pathways, recovery of function depends on the capacity of surviving anatomical resources to recover and repair in response to task-specific training. One such area implicated in poststroke reorganization to promote recovery of upper extremity recovery is the premotor cortex (PMC). This study reviews the role of distinct subdivisions of PMC: dorsal (PMd) and ventral (PMv) premotor cortices as critical anatomical and physiological nodes within the neural networks for the control and learning of goal-oriented reach and grasp actions in healthy individuals and individuals with stroke. Based on evidence emerging from studies of intrinsic and extrinsic connectivity, transcranial magnetic stimulation, functional neuroimaging, and experimental studies in animals and humans, the authors propose 2 distinct patterns of reorganization that differentially engage ipsilesional and contralesional PMC. Research directions that may offer further insights into the role of PMC in motor control, learning, and poststroke recovery are also proposed. This research may facilitate neuroplasticity for maximal recovery of function following brain injury. PMID:21926382

  9. Epigenetic Regulation of a Brain-specific Glycosyltransferase N-Acetylglucosaminyltransferase-IX (GnT-IX) by Specific Chromatin Modifiers*

    PubMed Central

    Kizuka, Yasuhiko; Kitazume, Shinobu; Okahara, Kyohei; Villagra, Alejandro; Sotomayor, Eduardo M.; Taniguchi, Naoyuki

    2014-01-01

    Expression of glycosyltransferase genes is essential for glycosylation. However, the detailed mechanisms of how glycosyltransferase gene expression is regulated in a specific tissue or during disease progression are poorly understood. In particular, epigenetic studies of glycosyltransferase genes are limited, although epigenetic mechanisms, such as histone and DNA modifications, are central to establish tissue-specific gene expression. We previously found that epigenetic histone activation is essential for brain-specific expression of N-acetylglucosaminyltransferase-IX (GnT-IX, also designated GnT-Vb), but the mechanism of brain-specific chromatin activation around GnT-IX gene (Mgat5b) has not been clarified. To reveal the mechanisms regulating the chromatin surrounding GnT-IX, we have investigated the epigenetic factors that are specifically involved with the mouse GnT-IX locus by comparing their involvement with other glycosyltransferase loci. We first found that a histone deacetylase (HDAC) inhibitor enhanced the expression of GnT-IX but not of other glycosyltransferases tested. By overexpression and knockdown of a series of HDACs, we found that HDAC11 silenced GnT-IX. We also identified the O-GlcNAc transferase (OGT) and ten-eleven translocation-3 (TET3) complex as a specific chromatin activator of GnT-IX gene. Moreover, chromatin immunoprecipitation (ChIP) analysis in combination with OGT or TET3 knockdown showed that this OGT-TET3 complex facilitates the binding of a potent transactivator, NeuroD1, to the GnT-IX promoter, suggesting that epigenetic chromatin activation by the OGT-TET3 complex is a prerequisite for the efficient binding of NeuroD1. These results reveal a new epigenetic mechanism of brain-specific GnT-IX expression regulated by defined chromatin modifiers, providing new insights into the tissue-specific expression of glycosyltransferases. PMID:24619417

  10. Female-specific target sites for both oestrogen and androgen in the teleost brain.

    PubMed

    Hiraki, Towako; Takeuchi, Akio; Tsumaki, Takayasu; Zempo, Buntaro; Kanda, Shinji; Oka, Yoshitaka; Nagahama, Yoshitaka; Okubo, Kataaki

    2012-12-22

    To dissect the molecular and cellular basis of sexual differentiation of the teleost brain, which maintains marked sexual plasticity throughout life, we examined sex differences in neural expression of all subtypes of nuclear oestrogen and androgen receptors (ER and AR) in medaka. All receptors were differentially expressed between the sexes in specific nuclei in the forebrain. The most pronounced sex differences were found in several nuclei in the ventral telencephalic and preoptic areas, where ER and AR expression were prominent in females but almost completely absent in males, indicating that these nuclei represent female-specific target sites for both oestrogen and androgen in the brain. Subsequent analyses revealed that the female-specific expression of ER and AR is not under the direct control of sex-linked genes but is instead regulated positively by oestrogen and negatively by androgen in a transient and reversible manner. Taken together, the present study demonstrates that sex-specific target sites for both oestrogen and androgen occur in the brain as a result of the activational effects of gonadal steroids. The consequent sex-specific but reversible steroid sensitivity of the adult brain probably contributes substantially to the process of sexual differentiation and the persistent sexual plasticity of the teleost brain. PMID:23075834

  11. Female-specific target sites for both oestrogen and androgen in the teleost brain

    PubMed Central

    Hiraki, Towako; Takeuchi, Akio; Tsumaki, Takayasu; Zempo, Buntaro; Kanda, Shinji; Oka, Yoshitaka; Nagahama, Yoshitaka; Okubo, Kataaki

    2012-01-01

    To dissect the molecular and cellular basis of sexual differentiation of the teleost brain, which maintains marked sexual plasticity throughout life, we examined sex differences in neural expression of all subtypes of nuclear oestrogen and androgen receptors (ER and AR) in medaka. All receptors were differentially expressed between the sexes in specific nuclei in the forebrain. The most pronounced sex differences were found in several nuclei in the ventral telencephalic and preoptic areas, where ER and AR expression were prominent in females but almost completely absent in males, indicating that these nuclei represent female-specific target sites for both oestrogen and androgen in the brain. Subsequent analyses revealed that the female-specific expression of ER and AR is not under the direct control of sex-linked genes but is instead regulated positively by oestrogen and negatively by androgen in a transient and reversible manner. Taken together, the present study demonstrates that sex-specific target sites for both oestrogen and androgen occur in the brain as a result of the activational effects of gonadal steroids. The consequent sex-specific but reversible steroid sensitivity of the adult brain probably contributes substantially to the process of sexual differentiation and the persistent sexual plasticity of the teleost brain. PMID:23075834

  12. Does perception of biological motion rely on specific brain regions?

    PubMed

    Grzes, J; Fonlupt, P; Bertenthal, B; Delon-Martin, C; Segebarth, C; Decety, J

    2001-05-01

    Perception of biological motions plays a major adaptive role in identifying, interpreting, and predicting the actions of others. It may therefore be hypothesized that the perception of biological motions is subserved by a specific neural network. Here we used fMRI to verify this hypothesis. In a group of 10 healthy volunteers, we explored the hemodynamic responses to seven types of visual motion displays: drifting random dots, random dot cube, random dot cube with masking elements, upright point-light walker, inverted point-light walker, upright point-light walker display with masking elements, and inverted point-light walker display with masking elements. A gradient in activation was observed in the occipitotemporal junction. The responses to rigid motion were localized posteriorly to those responses elicited by nonrigid motions. Our results demonstrate that in addition to the posterior portion of superior temporal sulcus, the left intraparietal cortex is involved in the perception of nonrigid biological motions. PMID:11304074

  13. Machine-learning to characterise neonatal functional connectivity in the preterm brain

    PubMed Central

    Ball, G.; Aljabar, P.; Arichi, T.; Tusor, N.; Cox, D.; Merchant, N.; Nongena, P.; Hajnal, J.V.; Edwards, A.D.; Counsell, S.J.

    2016-01-01

    Brain development is adversely affected by preterm birth. Magnetic resonance image analysis has revealed a complex fusion of structural alterations across all tissue compartments that are apparent by term-equivalent age, persistent into adolescence and adulthood, and associated with wide-ranging neurodevelopment disorders. Although functional MRI has revealed the relatively advanced organisational state of the neonatal brain, the full extent and nature of functional disruptions following preterm birth remain unclear. In this study, we apply machine-learning methods to compare whole-brain functional connectivity in preterm infants at term-equivalent age and healthy term-born neonates in order to test the hypothesis that preterm birth results in specific alterations to functional connectivity by term-equivalent age. Functional connectivity networks were estimated in 105 preterm infants and 26 term controls using group-independent component analysis and a graphical lasso model. A random forest–based feature selection method was used to identify discriminative edges within each network and a nonlinear support vector machine was used to classify subjects based on functional connectivity alone. We achieved 80% cross-validated classification accuracy informed by a small set of discriminative edges. These edges connected a number of functional nodes in subcortical and cortical grey matter, and most were stronger in term neonates compared to those born preterm. Half of the discriminative edges connected one or more nodes within the basal ganglia. These results demonstrate that functional connectivity in the preterm brain is significantly altered by term-equivalent age, confirming previous reports of altered connectivity between subcortical structures and higher-level association cortex following preterm birth. PMID:26341027

  14. Machine-learning to characterise neonatal functional connectivity in the preterm brain.

    PubMed

    Ball, G; Aljabar, P; Arichi, T; Tusor, N; Cox, D; Merchant, N; Nongena, P; Hajnal, J V; Edwards, A D; Counsell, S J

    2016-01-01

    Brain development is adversely affected by preterm birth. Magnetic resonance image analysis has revealed a complex fusion of structural alterations across all tissue compartments that are apparent by term-equivalent age, persistent into adolescence and adulthood, and associated with wide-ranging neurodevelopment disorders. Although functional MRI has revealed the relatively advanced organisational state of the neonatal brain, the full extent and nature of functional disruptions following preterm birth remain unclear. In this study, we apply machine-learning methods to compare whole-brain functional connectivity in preterm infants at term-equivalent age and healthy term-born neonates in order to test the hypothesis that preterm birth results in specific alterations to functional connectivity by term-equivalent age. Functional connectivity networks were estimated in 105 preterm infants and 26 term controls using group-independent component analysis and a graphical lasso model. A random forest-based feature selection method was used to identify discriminative edges within each network and a nonlinear support vector machine was used to classify subjects based on functional connectivity alone. We achieved 80% cross-validated classification accuracy informed by a small set of discriminative edges. These edges connected a number of functional nodes in subcortical and cortical grey matter, and most were stronger in term neonates compared to those born preterm. Half of the discriminative edges connected one or more nodes within the basal ganglia. These results demonstrate that functional connectivity in the preterm brain is significantly altered by term-equivalent age, confirming previous reports of altered connectivity between subcortical structures and higher-level association cortex following preterm birth. PMID:26341027

  15. Brain Gut Microbiome Interactions and Functional Bowel Disorders

    PubMed Central

    Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

    2014-01-01

    Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions. PMID:24583088

  16. Ammonium channel expression is essential for brain development and function in the larva of Ciona intestinalis.

    PubMed

    Marino, Rita; Melillo, Daniela; Di Filippo, Miriam; Yamada, Atsuko; Pinto, Maria Rosaria; De Santis, Rosaria; Brown, Euan R; Matassi, Giorgio

    2007-07-01

    Ammonium uptake into the cell is known to be mediated by ammonium transport (Amt) proteins, which are present in all domains of life. The physiological role of Amt proteins remains elusive; indeed, loss-of-function experiments suggested that Amt proteins do not play an essential role in bacteria, yeast, and plants. Here we show that the reverse holds true in the tunicate Ciona intestinalis. The genome of C. intestinalis contains two AMT genes, Ci-AMT1a and Ci-AMT1b, which we show derive from an ascidian-specific gene duplication. We analyzed Ci-AMT expression during embryo development. Notably, Ci-AMT1a is expressed in the larval brain in a small number of cells defining a previously unseen V-shaped territory; these cells connect the brain cavity to the external environment. We show that the knockdown of Ci-AMT1a impairs the formation of the brain cavity and consequently the function of the otolith, the gravity-sensing organ contained in it. We speculate that the normal mechanical functioning (flotation and free movement) of the otolith may require a close regulation of ammonium salt(s) concentration in the brain cavity, because ammonium is known to affect both fluid density and viscosity; the cells forming the V territory may act as a conduit in achieving such a regulation. PMID:17480017

  17. Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain

    PubMed Central

    Williams, Gemma; Fabrizi, Lorenzo; Meek, Judith; Jackson, Deborah; Tracey, Irene; Robertson, Nicola; Slater, Rebeccah; Fitzgerald, Maria

    2015-01-01

    Aim Despite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants. Methods We studied 19 term infants with a mean age of 13days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas. Results Distinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant. Conclusion Distinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain. PMID:25358870

  18. Linking human brain local activity fluctuations to structural and functional network architectures

    PubMed Central

    Baria, A.T.; Mansour, A.; Huang, L.; Baliki, M.N.; Cecchi, G.A.; Mesulam, M.M.; Apkarian, A.V.

    2013-01-01

    Activity of cortical local neuronal populations fluctuates continuously, and a large proportion of these fluctuations are shared across populations of neurons. Here we seek organizational rules that link these two phenomena. Using neuronal activity, as identified by functional MRI (fMRI) and for a given voxel or brain region, we derive a single measure of full bandwidth brain-oxygenation-level-dependent (BOLD) fluctuations by calculating the slope, α, for the log-linear power spectrum. For the same voxel or region, we also measure the temporal coherence of its fluctuations to other voxels or regions, based on exceeding a given threshold, Θ, for zero lag correlation, establishing functional connectivity between pairs of neuronal populations. From resting state fMRI, we calculated whole-brain group-averaged maps for α and for functional connectivity. Both maps showed similar spatial organization, with a correlation coefficient of 0.75 between the two parameters across all brain voxels, as well as variability with hodology. A computational model replicated the main results, suggesting that synaptic low-pass filtering can account for these interrelationships. We also investigated the relationship between α and structural connectivity, as determined by diffusion tensor imaging-based tractography. We observe that the correlation between α and connectivity depends on attentional state; specifically, α correlated more highly to structural connectivity during rest than while attending to a task. Overall, these results provide global rules for the dynamics between frequency characteristics of local brain activity and the architecture of underlying brain networks. PMID:23396160

  19. Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain

    PubMed Central

    Herbst, Eric AF; Holloway, Graham P

    2015-01-01

    Abstract Mitochondria function as the core energy providers in the brain and symptoms of neurodegenerative diseases are often attributed to their dysregulation. Assessing mitochondrial function is classically performed in isolated mitochondria; however, this process requires significant isolation time, demand for abundant tissue and disruption of the cooperative mitochondrial reticulum, all of which reduce reliability when attempting to assess in vivo mitochondrial bioenergetics. Here we introduce a method that advances the assessment of mitochondrial respiration in the brain by permeabilizing existing brain tissue to grant direct access to the mitochondrial reticulum in situ. The permeabilized brain preparation allows for instant analysis of mitochondrial function with unaltered mitochondrial morphology using significantly small sample sizes (∼2 mg), which permits the analysis of mitochondrial function in multiple subregions within a single mouse brain. Here this technique was applied to assess regional variation in brain mitochondrial function with acute ischaemia–reperfusion injuries and to determine the role of reactive oxygen species in exacerbating dysfunction through the application of a transgenic mouse model overexpressing catalase within mitochondria. Through creating accessibility to small regions for the investigation of mitochondrial function, the permeabilized brain preparation enhances the capacity for examining regional differences in mitochondrial regulation within the brain, as the majority of genetic models used for unique approaches exist in the mouse model. PMID:25529987

  20. Characterization of the novel protein P9TLDR (temporal lobe down-regulated) with a brain-site-specific gene expression modality in Alzheimer's disease brain.

    PubMed

    Yokota, Tomoko; Akatsu, Hiroyasu; Miyauchi, Takashi; Heese, Klaus

    2012-12-14

    Alzheimer's disease (AD) is an aging-related neurodegenerative disorder characterized by irreversible loss of higher cognitive functions. The disease is characterized by the presence of amyloid plaques and neurofibrillary tangles (NFT). In the current study we isolated from an intra-cerebral brain-site-specific (AD temporal lobe vs. AD occipital lobe) polymerase chain reaction (PCR)-select cDNA suppression subtractive hybridization (PCR-cDNA-SSH) expression analysis the novel gene P9TLDR, potentially a microtubule-associated protein involved in neuronal migration, with an altered expression pattern: down-regulated in the temporal lobe cortex of early stage AD brains. In an in vitro AD-related cell model, amyloid-? peptide (A?)-treated neurons, reduced P9TLDR expression correlated with increased tau protein phosphorylation. In conclusion, interference with the P9TLDR signalling pathways might be a therapeutic strategy for the treatment of AD. PMID:23159938

  1. [Brain renin-angiotensin-aldosterone system and cognitive function].

    PubMed

    Horiuchi, Masatsugu

    2014-04-01

    The presence of hypertension and other vascular risk factors such as diabetes mellitus is known to be associated with the decreased cognitive function. Blood pressure-lowering with antihypertensive agents was suggested to reduce the risk of dementia or cognitive decline. The renin-angiotensin-aldosterone system plays a role not only in the cardiovascular system including blood pressure regulation, but also in the central nervous system. The possible beneficial effects of ARB and ACE inhibitor on cognitive function are also becoming highlighted in the clinical field. This article reviews the effects of regulation of activation of angiotensin II receptor subtypes, and ACE2/angiotensin- (1-7)/Mas receptor on ischemic brain damage and cognitive function. PMID:24796091

  2. Large-Scale Functional Brain Network Reorganization During Taoist Meditation.

    PubMed

    Jao, Tun; Li, Chia-Wei; Vértes, Petra E; Wu, Changwei Wesley; Achard, Sophie; Hsieh, Chao-Hsien; Liou, Chien-Hui; Chen, Jyh-Horng; Bullmore, Edward T

    2016-02-01

    Meditation induces a distinct and reversible mental state that provides insights into brain correlates of consciousness. We explored brain network changes related to meditation by graph theoretical analysis of resting-state functional magnetic resonance imaging data. Eighteen Taoist meditators with varying levels of expertise were scanned using a within-subjects counterbalanced design during resting and meditation states. State-related differences in network topology were measured globally and at the level of individual nodes and edges. Although measures of global network topology, such as small-worldness, were unchanged, meditation was characterized by an extensive and expertise-dependent reorganization of the hubs (highly connected nodes) and edges (functional connections). Areas of sensory cortex, especially the bilateral primary visual and auditory cortices, and the bilateral temporopolar areas, which had the highest degree (or connectivity) during the resting state, showed the biggest decrease during meditation. Conversely, bilateral thalamus and components of the default mode network, mainly the bilateral precuneus and posterior cingulate cortex, had low degree in the resting state but increased degree during meditation. Additionally, these changes in nodal degree were accompanied by reorganization of anatomical orientation of the edges. During meditation, long-distance longitudinal (antero-posterior) edges increased proportionally, whereas orthogonal long-distance transverse (right-left) edges connecting bilaterally homologous cortices decreased. Our findings suggest that transient changes in consciousness associated with meditation introduce convergent changes in the topological and spatial properties of brain functional networks, and the anatomical pattern of integration might be as important as the global level of integration when considering the network basis for human consciousness. PMID:26165867

  3. Behavioral Relevance of the Dynamics of the Functional Brain Connectome

    PubMed Central

    Jia, Hao

    2014-01-01

    Abstract While many previous studies assumed the functional connectivity (FC) between brain regions to be stationary, recent studies have demonstrated that FC dynamically varies across time. However, two challenges have limited the interpretability of dynamic FC information. First, a principled framework for selecting the temporal extent of the window used to examine the dynamics is lacking and this has resulted in ad-hoc selections of window lengths and subsequent divergent results. Second, it is unclear whether there is any behavioral relevance to the dynamics of the functional connectome in addition to that obtained from conventional static FC (SFC). In this work, we address these challenges by first proposing a principled framework for selecting the extent of the temporal windows in a dynamic and data-driven fashion based on statistical tests of the stationarity of time series. Further, we propose a method involving three levels of clustering—across space, time, and subjects—which allow for group-level inferences of the dynamics. Next, using a large resting-state functional magnetic resonance imaging and behavioral dataset from the Human Connectome Project, we demonstrate that metrics derived from dynamic FC can explain more than twice the variance in 75 behaviors across different domains (alertness, cognition, emotion, and personality traits) as compared with SFC in healthy individuals. Further, we found that individuals with brain networks exhibiting greater dynamics performed more favorably in behavioral tasks. This indicates that the ease with which brain regions engage or disengage may provide potential biomarkers for disorders involving altered neural circuitry. PMID:25163490

  4. Critical periods of brain growth and cognitive function in children.

    PubMed

    Gale, Catharine R; O'Callaghan, Finbar J; Godfrey, Keith M; Law, Catherine M; Martyn, Christopher N

    2004-02-01

    There is evidence that IQ tends to be higher in those who were heavier at birth or who grew taller in childhood and adolescence. Although these findings imply that growth in both foetal and postnatal life influences cognitive performance, little is known about the relative importance of brain growth during different periods of development. We investigated the relationship between brain growth in different periods of pre- and postnatal life and cognitive function in 221 9-year-old children whose mothers had taken part in a study of nutrition in pregnancy and whose head circumference had been measured at 18 weeks gestation, birth and 9 months of age. Cognitive function of the children and their mothers was assessed with the Wechsler Abbreviated Scale of Intelligence. Full-scale IQ at age 9 years rose by 1.98 points [95% confidence interval (CI) 0.34 to 3.62] for each SD increase in head circumference at 9 months and by 2.87 points (95% CI 1.05 to 4.69) for each SD increase in head circumference at 9 years of age, after adjustment for sex, number of older siblings, maternal IQ, age, education, social class, duration of breastfeeding and history of low mood in the post-partum period. Postnatal head growth was significantly greater in children whose mothers were educated to degree level or of higher socio-economic status. There was no relation between IQ and measurements of head size at 18 weeks gestation or at birth. These results suggest that brain growth during infancy and early childhood is more important than growth during foetal life in determining cognitive function. PMID:14645144

  5. Mitochondrial activity and brain functions during cortical depolarization

    NASA Astrophysics Data System (ADS)

    Mayevsky, Avraham; Sonn, Judith

    2008-12-01

    Cortical depolarization (CD) of the cerebral cortex could be developed under various pathophysiological conditions. In animal models, CD was recorded under partial or complete ischemia as well as when cortical spreading depression (SD) was induced externally or by internal stimulus. The development of CD in patients and the changes in various metabolic parameters, during CD, was rarely reported. Brain metabolic, hemodynamic, ionic and electrical responses to the CD event are dependent upon the O2 balance in the tissue. When the O2 balance is negative (i.e. ischemia), the CD process will be developed due to mitochondrial dysfunction, lack of energy and the inhibition of Na+-K+-ATPase. In contradiction, when oxygen is available (i.e. normoxia) the development of CD after induction of SD will accelerate mitochondrial respiration for retaining ionic homeostasis and normal brain functions. We used the multiparametric monitoring approach that enable real time monitoring of mitochondrial NADH redox state, microcirculatory blood flow and oxygenation, extracellular K+, Ca2+, H+ levels, DC steady potential and electrocorticogram (ECoG). This monitoring approach, provide a unique tool that has a significant value in analyzing the pathophysiology of the brain when SD developed under normoxia, ischemia, or hypoxia. We applied the same monitoring approach to patients suffered from severe head injury or exposed to neurosurgical procedures.

  6. Functional Characterization of Germline Mutations in PDGFB and PDGFRB in Primary Familial Brain Calcification

    PubMed Central

    Andaloussi Mäe, Maarja; Nahar, Khayrun; Hornemann, Simone; Kenkel, David; Cunha, Sara I.; Lennartsson, Johan; Boss, Andreas; Heldin, Carl-Henrik; Keller, Annika; Betsholtz, Christer

    2015-01-01

    Primary Familial Brain Calcification (PFBC), a neurodegenerative disease characterized by progressive pericapillary calcifications, has recently been linked to heterozygous mutations in PDGFB and PDGFRB genes. Here, we functionally analyzed several of these mutations in vitro. All six analyzed PDGFB mutations led to complete loss of PDGF-B function either through abolished protein synthesis or through defective binding and/or stimulation of PDGF-Rβ. The three analyzed PDGFRB mutations had more diverse consequences. Whereas PDGF-Rβ autophosphorylation was almost totally abolished in the PDGFRB L658P mutation, the two sporadic PDGFRB mutations R987W and E1071V caused reductions in protein levels and specific changes in the intensity and kinetics of PLCγ activation, respectively. Since at least some of the PDGFB mutations were predicted to act through haploinsufficiency, we explored the consequences of reduced Pdgfb or Pdgfrb transcript and protein levels in mice. Heterozygous Pdgfb or Pdgfrb knockouts, as well as double Pdgfb+/-;Pdgfrb+/- mice did not develop brain calcification, nor did Pdgfrbredeye/redeye mice, which show a 90% reduction of PDGFRβ protein levels. In contrast, Pdgfbret/ret mice, which have altered tissue distribution of PDGF-B protein due to loss of a proteoglycan binding motif, developed brain calcifications. We also determined pericyte coverage in calcification-prone and non-calcification-prone brain regions in Pdgfbret/ret mice. Surprisingly and contrary to our hypothesis, we found that the calcification-prone brain regions in Pdgfbret/ret mice model had a higher pericyte coverage and a more intact blood-brain barrier (BBB) compared to non-calcification-prone brain regions. While our findings provide clear evidence that loss-of-function mutations in PDGFB or PDGFRB cause PFBC, they also demonstrate species differences in the threshold levels of PDGF-B/PDGF-Rβ signaling that protect against small-vessel calcification in the brain. They further implicate region-specific susceptibility factor(s) in PFBC pathogenesis that are distinct from pericyte and BBB deficiency. PMID:26599395

  7. RESTING STATE INTER AND INTRA HEMISPHERIC HUMAN BRAIN FUNCTIONAL CONNECTIVITY

    PubMed Central

    Razlighi, Qolamreza R.; Steffener, Jason; Habeck, Christian; Laine, Andrew; Stern, Yaakov

    2014-01-01

    Resting-state functional connectivity between neuroanatomical regions has attracted significant attention in recent years. In the process of obtaining the resting-state functional connectivity map of the human brain from blood-oxygen-level-dependent fMRI signals, it is common to average the signals from left and right hemispheres. This averaging can introduce unappreciated complexities and unintended consequences not related to the research question of interest. In this paper, we mathematically demonstrate that measures of functional connectivity obtained by averaging homologous regions from the both hemispheres become undesirably dependent on four inter-hemispheric connectivity measures. We explore this finding in real-world fMRI data from 25 healthy young participants. We show that inter-hemispheric averaging has a mixed effect on the results and may introduce correlation artifacts to the connectivity map. Furthermore, we show mathematically and demonstrate with Monte Carlo simulations of null data that inter-hemispheric averaging will not alter human brain connectivity map at rest only and if only there are no inter-hemispheric correlations. PMID:24111236

  8. 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

  9. Crossed-Brain Representation of Verbal and Nonverbal Functions

    PubMed Central

    Matute, Esmeralda; Ardila, Alfredo; Rosselli, Monica; Molina Del Rio, Jahaziel; López Elizalde, Ramiro; López, Manuel; Ontiveros, Angel

    2015-01-01

    A 74-year-old, left-handed man presented with a rapidly evolving loss of strength in his right leg associated with difficulty in walking. MR images disclosed an extensive left hemisphere tumor. A neuropsychological examination revealed that language was broadly normal but that the patient presented with severe nonlinguistic abnormalities, including hemineglect (both somatic and spatial), constructional defects, and general spatial disturbances; symptoms were usually associated with right hemisphere pathologies. No ideomotor apraxia was found. The implications of crossed-brain representations of verbal and nonverbal functions are analyzed. PMID:25802778

  10. Functional brain networks underlying detection and integration of disconfirmatory evidence.

    PubMed

    Lavigne, Katie M; Metzak, Paul D; Woodward, Todd S

    2015-05-15

    Processing evidence that disconfirms a prior interpretation is a fundamental aspect of belief revision, and has clear social and clinical relevance. This complex cognitive process requires (at minimum) an alerting stage and an integration stage, and in the current functional magnetic resonance imaging (fMRI) study, we used multivariate analysis methodology on two datasets in an attempt to separate these sequentially-activated cognitive stages and link them to distinct functional brain networks. Thirty-nine healthy participants completed one of two versions of an evidence integration experiment involving rating two consecutive animal images, both of which consisted of two intact images of animal faces morphed together at different ratios (e.g., 70/30 bird/dolphin followed by 10/90 bird/dolphin). The two versions of the experiment differed primarily in terms of stimulus presentation and timing, which facilitated functional interpretation of brain networks based on differences in the hemodynamic response shapes between versions. The data were analyzed using constrained principal component analysis for fMRI (fMRI-CPCA), which allows distinct, simultaneously active task-based networks to be separated, and these were interpreted using both temporal (task-based hemodynamic response shapes) and spatial (dominant brain regions) information. Three networks showed increased activity during integration of disconfirmatory relative to confirmatory evidence: (1) a network involved in alerting to the requirement to revise an interpretation, identified as the salience network (dorsal anterior cingulate cortex and bilateral insula); (2) a sensorimotor response-related network (pre- and post-central gyri, supplementary motor area, and thalamus); and (3) an integration network involving rostral prefrontal, orbitofrontal and posterior parietal cortex. These three networks were staggered in their peak activity (alerting, responding, then integrating), but at certain time points (e.g., 17s after trial onset) the hemodynamic responses associated with all three networks were simultaneously active. These findings highlight distinct cognitive processes and corresponding functional brain networks underlying stages of disconfirmatory evidence integration, and demonstrate the power of multivariate and multi-experiment methodology in cognitive neuroscience. PMID:25731997

  11. Functional community analysis of brain: a new approach for EEG-based investigation of the brain pathology.

    PubMed

    Ahmadlou, Mehran; Adeli, Hojjat

    2011-09-15

    Analysis of structure of the brain functional connectivity (SBFC) is a fundamental issue for understanding of the brain cognition as well as the pathology of brain disorders. Analysis of communities among sub-parts of a system is increasingly used for social, ecological, and other networks. This paper presents a new methodology for investigation of the SBFC and understanding of the brain based on graph theory and community pattern analysis of functional connectivity graph of the brain obtained from encephalograms (EEGs). The methodology consists of three main parts: fuzzy synchronization likelihood (FSL), community partitioning, and decisions based on partitions. As an example application, the methodology is applied to analysis of brain of patients with attention deficit/hyperactivity disorder (ADHD) and the problem of discrimination of ADHD EEGs from healthy (non-ADHD) EEGs. PMID:21586331

  12. Specific Binding and Characteristics of 18β-Glycyrrhetinic Acid in Rat Brain

    PubMed Central

    Mizoguchi, Kazushige; Kanno, Hitomi; Ikarashi, Yasushi; Kase, Yoshio

    2014-01-01

    18β-Glycyrrhetinic acid (GA) is the aglycone of glycyrrhizin that is a component of Glycyrrhiza, and has several pharmacological actions in the central nervous system. Recently, GA has been demonstrated to reach the brain by crossing the blood-brain barrier in rats after oral administration of a Glycyrrhiza-containing traditional Japanese medicine, yokukansan. These findings suggest that there are specific binding sites for GA in the brain. Here we show evidence that [3H]GA binds specifically to several brain areas by quantitative autoradiography; the density was higher in the hippocampus, moderate in the caudate putamen, nucleus accumbens, amygdala, olfactory bulb, cerebral cortex, thalamus, and mid brain, and lower in the brain stem and cerebellum. Several kinds of steroids, gap junction-blocking reagents, glutamate transporter-recognized compounds, and glutamate receptor agonists did not inhibit the [3H]GA binding. Microautoradiography showed that the [3H]GA signals in the hippocampus were distributed in small non-neuronal cells similar to astrocytes. Immunohistochemical analysis revealed that immunoreactivity of 11β-hydroxysteroid dehydrogenase type-1 (11β-HSD1), a defined molecule recognized by GA, was detected mainly in neurons, moderately in astrocytes, and very slightly in microglial cells, of the hippocampus. These results demonstrate that specific binding sites for GA exist in rat brain tissue, and suggest that the pharmacological actions of GA may be related to 11β-HSD1 in astrocytes. This finding provides important information to understand the pharmacology of GA in the brain. PMID:24752617

  13. Highly adaptive tests for group differences in brain functional connectivity

    PubMed Central

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that “there is currently no unique solution, but a spectrum of related methods and analytical strategies” to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not only easy to use, but also high-powered robustly across various scenarios. The usage and advantages of these novel tests are demonstrated on an Alzheimer's disease dataset and simulated data. PMID:26740916

  14. Highly adaptive tests for group differences in brain functional connectivity.

    PubMed

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that "there is currently no unique solution, but a spectrum of related methods and analytical strategies" to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not only easy to use, but also high-powered robustly across various scenarios. The usage and advantages of these novel tests are demonstrated on an Alzheimer's disease dataset and simulated data. PMID:26740916

  15. Analyzing the association between functional connectivity of the brain and intellectual performance.

    PubMed

    Pamplona, Gustavo S P; Santos Neto, Grson S; Rosset, Sara R E; Rogers, Baxter P; Salmon, Carlos E G

    2015-01-01

    Measurements of functional connectivity support the hypothesis that the brain is composed of distinct networks with anatomically separated nodes but common functionality. A few studies have suggested that intellectual performance may be associated with greater functional connectivity in the fronto-parietal network and enhanced global efficiency. In this fMRI study, we performed an exploratory analysis of the relationship between the brain's functional connectivity and intelligence scores derived from the Portuguese language version of the Wechsler Adult Intelligence Scale (WAIS-III) in a sample of 29 people, born and raised in Brazil. We examined functional connectivity between 82 regions, including graph theoretic properties of the overall network. Some previous findings were extended to the Portuguese-speaking population, specifically the presence of small-world organization of the brain and relationships of intelligence with connectivity of frontal, pre-central, parietal, occipital, fusiform and supramarginal gyrus, and caudate nucleus. Verbal comprehension was associated with global network efficiency, a new finding. PMID:25713528

  16. Functional and Structural Brain Plasticity Enhanced by Motor and Cognitive Rehabilitation in Multiple Sclerosis

    PubMed Central

    Prosperini, Luca; Piattella, Maria Cristina

    2015-01-01

    Rehabilitation is recognized to be important in ameliorating motor and cognitive functions, reducing disease burden, and improving quality of life in patients with multiple sclerosis (MS). In this systematic review, we summarize the existing evidences that motor and cognitive rehabilitation may enhance functional and structural brain plasticity in patients with MS, as assessed by means of the most advanced neuroimaging techniques, including diffusion tensor imaging and task-related and resting-state functional magnetic resonance imaging (MRI). In most cases, the rehabilitation program was based on computer-assisted/video game exercises performed in either an outpatient or home setting. Despite their heterogeneity, all the included studies describe changes in white matter microarchitecture, in task-related activation, and/or in functional connectivity following both task-oriented and selective training. When explored, relevant correlation between improved function and MRI-detected brain changes was often found, supporting the hypothesis that training-induced brain plasticity is specifically linked to the trained domain. Small sample sizes, lack of randomization and/or an active control group, as well as missed relationship between MRI-detected changes and clinical performance, are the major drawbacks of the selected studies. Knowledge gaps in this field of research are also discussed to provide a framework for future investigations. PMID:26064692

  17. Analyzing the association between functional connectivity of the brain and intellectual performance

    PubMed Central

    Pamplona, Gustavo S. P.; Santos Neto, Gérson S.; Rosset, Sara R. E.; Rogers, Baxter P.; Salmon, Carlos E. G.

    2015-01-01

    Measurements of functional connectivity support the hypothesis that the brain is composed of distinct networks with anatomically separated nodes but common functionality. A few studies have suggested that intellectual performance may be associated with greater functional connectivity in the fronto-parietal network and enhanced global efficiency. In this fMRI study, we performed an exploratory analysis of the relationship between the brain's functional connectivity and intelligence scores derived from the Portuguese language version of the Wechsler Adult Intelligence Scale (WAIS-III) in a sample of 29 people, born and raised in Brazil. We examined functional connectivity between 82 regions, including graph theoretic properties of the overall network. Some previous findings were extended to the Portuguese-speaking population, specifically the presence of small-world organization of the brain and relationships of intelligence with connectivity of frontal, pre-central, parietal, occipital, fusiform and supramarginal gyrus, and caudate nucleus. Verbal comprehension was associated with global network efficiency, a new finding. PMID:25713528

  18. Brain functional plasticity associated with the emergence of expertise in extreme language control.

    PubMed

    Hervais-Adelman, Alexis; Moser-Mercer, Barbara; Golestani, Narly

    2015-07-01

    We used functional magnetic resonance imaging (fMRI) to longitudinally examine brain plasticity arising from long-term, intensive simultaneous interpretation training. Simultaneous interpretation is a bilingual task with heavy executive control demands. We compared brain responses observed during simultaneous interpretation with those observed during simultaneous speech repetition (shadowing) in a group of trainee simultaneous interpreters, at the beginning and at the end of their professional training program. Age, sex and language-proficiency matched controls were scanned at similar intervals. Using multivariate pattern classification, we found distributed patterns of changes in functional responses from the first to second scan that distinguished the interpreters from the controls. We also found reduced recruitment of the right caudate nucleus during simultaneous interpretation as a result of training. Such practice-related change is consistent with decreased demands on multilingual language control as the task becomes more automatized with practice. These results demonstrate the impact of simultaneous interpretation training on the brain functional response in a cerebral structure that is not specifically linguistic, but that is known to be involved in learning, in motor control, and in a variety of domain-general executive functions. Along with results of recent studies showing functional and structural adaptations in the caudate nuclei of experts in a broad range of domains, our results underline the importance of this structure as a central node in expertise-related networks. PMID:25869858

  19. Motor skill failure or flow-experience? Functional brain asymmetry and brain connectivity in elite and amateur table tennis players.

    PubMed

    Wolf, Sebastian; Brölz, Ellen; Keune, Philipp M; Wesa, Benjamin; Hautzinger, Martin; Birbaumer, Niels; Strehl, Ute

    2015-02-01

    Functional hemispheric asymmetry is assumed to constitute one underlying neurophysiological mechanism of flow-experience and skilled psycho-motor performance in table tennis athletes. We hypothesized that when initiating motor execution during motor imagery, elite table tennis players show higher right- than left-hemispheric temporal activity and stronger right temporal-premotor than left temporal-premotor theta coherence compared to amateurs. We additionally investigated, whether less pronounced left temporal cortical activity is associated with more world rank points and more flow-experience. To this aim, electroencephalographic data were recorded in 14 experts and 15 amateur table tennis players. Subjects watched videos of an opponent serving a ball and were instructed to imagine themselves responding with a specific table tennis stroke. Alpha asymmetry scores were calculated by subtracting left from right hemispheric 8-13 Hz alpha power. 4-7 Hz theta coherence was calculated between temporal (T3/T4) and premotor (Fz) cortex. Experts showed a significantly stronger shift towards lower relative left-temporal brain activity compared to amateurs and a significantly stronger right temporal-premotor coherence than amateurs. The shift towards lower relative left-temporal brain activity in experts was associated with more flow-experience and lower relative left temporal activity was correlated with more world rank points. The present findings suggest that skilled psycho-motor performance in elite table tennis players reflect less desynchronized brain activity at the left hemisphere and more coherent brain activity between fronto-temporal and premotor oscillations at the right hemisphere. This pattern probably reflect less interference of irrelevant communication of verbal-analytical with motor-control mechanisms which implies flow-experience and predict world rank in experts. PMID:25616246

  20. Context-specific behavioral surprise is differentially correlated with activity in anterior and posterior brain systems.

    PubMed

    Tobia, Michael J; Gläscher, Jan; Sommer, Tobias

    2016-06-15

    This experiment investigated whether behavioral surprise, an information-theoretic measure of the amount of memory and information integration associated with a response, is correlated with neural activity during decision making. A total of 30 participants (age 18-30) were scanned with functional MRI while completing 240 trials of a sequential decision-making task in which they selected an amount to wager from four possible values on each trial. Behavioral surprise was computed trial by trial using both context-free and context-specific formulations, and was used as a parametric modulator in functional MRI analyses. Whereas context-free surprise was not significantly correlated, two sets of clusters (P<0.005; cluster size>156 voxels) were differentially modulated by context-specific behavioral surprise. An anterior system comprised of the inferior frontal gyrus and anterior cingulate (each bilaterally), and left caudate, was positively modulated. A posterior system comprised of the posterior cingulate, parahippocampal gyrus and posterior hippocampus (each bilaterally), and left angular gyrus, was negatively modulated. These anticorrelated systems indicate that more surprising (resource demanding) actions recruit greater activity from the anterior system and less activity from the posterior system and less surprising actions (memory-guided) recruit greater activity from the posterior system and less activity from the anterior system. These results show that context-specific behavioral surprise is a unique neural signal and may be related to mechanisms for both cognitive control and memory-guided behavior, and support contemporary theories that the brain is a statistical observer of external and internal events. PMID:27110868

  1. Testing Group Differences in Brain Functional Connectivity: Using Correlations or Partial Correlations?

    PubMed Central

    Kim, Junghi; Wozniak, Jeffrey R.; Mueller, Bryon A.

    2015-01-01

    Abstract Resting-state functional magnetic resonance imaging allows one to study brain functional connectivity, partly motivated by evidence that patients with complex disorders, such as Alzheimer's disease, may have altered functional brain connectivity patterns as compared with healthy subjects. A functional connectivity network describes statistical associations of the neural activities among distinct and distant brain regions. Recently, there is a major interest in group-level functional network analysis; however, there is a relative lack of studies on statistical inference, such as significance testing for group comparisons. In particular, it is still debatable which statistic should be used to measure pairwise associations as the connectivity weights. Many functional connectivity studies have used either (full or marginal) correlations or partial correlations for pairwise associations. This article investigates the performance of using either correlations or partial correlations for testing group differences in brain connectivity, and how sparsity levels and topological structures of the connectivity would influence statistical power to detect group differences. Our results suggest that, in general, testing group differences in networks deviates from estimating networks. For example, high regularization in both covariance matrices and precision matrices may lead to higher statistical power; in particular, optimally selected regularization (e.g., by cross-validation or even at the true sparsity level) on the precision matrices with small estimation errors may have low power. Most importantly, and perhaps surprisingly, using either correlations or partial correlations may give very different testing results, depending on which of the covariance matrices and the precision matrices are sparse. Specifically, if the precision matrices are sparse, presumably and arguably a reasonable assumption, then using correlations often yields much higher powered and more stable testing results than using partial correlations; the conclusion is reversed if the covariance matrices, not the precision matrices, are sparse. These results may have useful implications to future studies on testing functional connectivity differences. PMID:25492804

  2. Testing group differences in brain functional connectivity: using correlations or partial correlations?

    PubMed

    Kim, Junghi; Wozniak, Jeffrey R; Mueller, Bryon A; Pan, Wei

    2015-05-01

    Resting-state functional magnetic resonance imaging allows one to study brain functional connectivity, partly motivated by evidence that patients with complex disorders, such as Alzheimer's disease, may have altered functional brain connectivity patterns as compared with healthy subjects. A functional connectivity network describes statistical associations of the neural activities among distinct and distant brain regions. Recently, there is a major interest in group-level functional network analysis; however, there is a relative lack of studies on statistical inference, such as significance testing for group comparisons. In particular, it is still debatable which statistic should be used to measure pairwise associations as the connectivity weights. Many functional connectivity studies have used either (full or marginal) correlations or partial correlations for pairwise associations. This article investigates the performance of using either correlations or partial correlations for testing group differences in brain connectivity, and how sparsity levels and topological structures of the connectivity would influence statistical power to detect group differences. Our results suggest that, in general, testing group differences in networks deviates from estimating networks. For example, high regularization in both covariance matrices and precision matrices may lead to higher statistical power; in particular, optimally selected regularization (e.g., by cross-validation or even at the true sparsity level) on the precision matrices with small estimation errors may have low power. Most importantly, and perhaps surprisingly, using either correlations or partial correlations may give very different testing results, depending on which of the covariance matrices and the precision matrices are sparse. Specifically, if the precision matrices are sparse, presumably and arguably a reasonable assumption, then using correlations often yields much higher powered and more stable testing results than using partial correlations; the conclusion is reversed if the covariance matrices, not the precision matrices, are sparse. These results may have useful implications to future studies on testing functional connectivity differences. PMID:25492804

  3. Modalities of Thinking: State and Trait Effects on Cross-Frequency Functional Independent Brain Networks.

    PubMed

    Milz, Patricia; Pascual-Marqui, Roberto D; Lehmann, Dietrich; Faber, Pascal L

    2016-05-01

    Functional states of the brain are constituted by the temporally attuned activity of spatially distributed neural networks. Such networks can be identified by independent component analysis (ICA) applied to frequency-dependent source-localized EEG data. This methodology allows the identification of networks at high temporal resolution in frequency bands of established location-specific physiological functions. EEG measurements are sensitive to neural activity changes in cortical areas of modality-specific processing. We tested effects of modality-specific processing on functional brain networks. Phasic modality-specific processing was induced via tasks (state effects) and tonic processing was assessed via modality-specific person parameters (trait effects). Modality-specific person parameters and 64-channel EEG were obtained from 70 male, right-handed students. Person parameters were obtained using cognitive style questionnaires, cognitive tests, and thinking modality self-reports. EEG was recorded during four conditions: spatial visualization, object visualization, verbalization, and resting. Twelve cross-frequency networks were extracted from source-localized EEG across six frequency bands using ICA. RMANOVAs, Pearson correlations, and path modelling examined effects of tasks and person parameters on networks. Results identified distinct state- and trait-dependent functional networks. State-dependent networks were characterized by decreased, trait-dependent networks by increased alpha activity in sub-regions of modality-specific pathways. Pathways of competing modalities showed opposing alpha changes. State- and trait-dependent alpha were associated with inhibitory and automated processing, respectively. Antagonistic alpha modulations in areas of competing modalities likely prevent intruding effects of modality-irrelevant processing. Considerable research suggested alpha modulations related to modality-specific states and traits. This study identified the distinct electrophysiological cortical frequency-dependent networks within which they operate. PMID:26838167

  4. Resolving Anatomical and Functional Structure in Human Brain Organization: Identifying Mesoscale Organization in Weighted Network Representations

    PubMed Central

    Lohse, Christian; Bassett, Danielle S.; Lim, Kelvin O.; Carlson, Jean M.

    2014-01-01

    Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that enable us to identify and isolate structures associated with different weights. One such mesoscale structure is bipartivity, which quantifies the extent to which the brain is divided into two partitions with high connectivity between partitions and low connectivity within partitions. A second, complementary mesoscale structure is modularity, which quantifies the extent to which the brain is divided into multiple communities with strong connectivity within each community and weak connectivity between communities. Our methods lead to multi-resolution curves of these network diagnostics over a range of spatial, geometric, and structural scales. For statistical comparison, we contrast our results with those obtained for several benchmark null models. Our work demonstrates that multi-resolution diagnostic curves capture complex organizational profiles in weighted graphs. We apply these methods to the identification of resolution-specific characteristics of healthy weighted graph architecture and altered connectivity profiles in psychiatric disease. PMID:25275860

  5. Age-related changes in modular organization of human brain functional networks.

    PubMed

    Meunier, David; Achard, Sophie; Morcom, Alexa; Bullmore, Ed

    2009-02-01

    Graph theory allows us to quantify any complex system, e.g., in social sciences, biology or technology, that can be abstractly described as a set of nodes and links. Here we derived human brain functional networks from fMRI measurements of endogenous, low frequency, correlated oscillations in 90 cortical and subcortical regions for two groups of healthy (young and older) participants. We investigated the modular structure of these networks and tested the hypothesis that normal brain aging might be associated with changes in modularity of sparse networks. Newman's modularity metric was maximised and topological roles were assigned to brain regions depending on their specific contributions to intra- and inter-modular connectivity. Both young and older brain networks demonstrated significantly non-random modularity. The young brain network was decomposed into 3 major modules: central and posterior modules, which comprised mainly nodes with few inter-modular connections, and a dorsal fronto-cingulo-parietal module, which comprised mainly nodes with extensive inter-modular connections. The mean network in the older group also included posterior, superior central and dorsal fronto-striato-thalamic modules but the number of intermodular connections to frontal modular regions was significantly reduced, whereas the number of connector nodes in posterior and central modules was increased. PMID:19027073

  6. Distinct Functions of Glial and Neuronal Dystroglycan in the Developing and Adult Mouse Brain

    PubMed Central

    Satz, Jakob S.; Ostendorf, Adam P.; Hou, Shangwei; Turner, Amy; Kusano, Hajime; Lee, Jane C.; Turk, Rolf; Nguyen, Huy; Ross-Barta, Susan E.; Westra, Steve; Hoshi, Toshinori; Moore, Steven A.; Campbell, Kevin P.

    2010-01-01

    SUMMARY Cobblestone (type II) lissencephaly and mental retardation are characteristic features of a subset of congenital muscular dystrophies that include Walker-Warburg Syndrome, Muscle-Eye-Brain disease, and Fukuyama-type congenital muscular dystrophy. Although the majority of clinical cases are genetically undefined, several causative genes have been identified that encode known or putative glycosyltransferases in the biosynthetic pathway of dystroglycan. Here we test the effects of brain-specific deletion of dystroglycan, and show distinct functions for neuronal and glial dystroglycan. Deletion of dystroglycan in the whole brain produced glial/neuronal heterotopia resembling the cerebral cortex malformation in cobblestone lissencephaly. In wild-type mice, dystroglycan stabilizes the basement membrane of the glia limitans, thereby supporting the cortical infrastructure necessary for neuronal migration. This function depends on extracellular dystroglycan interactions, since the cerebral cortex developed normally in transgenic mice that lack the dystroglycan intracellular domain. Also, forebrain histogenesis was preserved in mice with neuron-specific deletion of dystroglycan, but hippocampal long-term potentiation was blunted, as is also the case in the Largemyd mouse, in which dystroglycan glycosylation is disrupted. Our findings provide genetic evidence that neuronal dystroglycan plays a role in synaptic plasticity and that glial dystroglycan is involved in forebrain development. Differences in dystroglycan glycosylation in distinct cell types of the CNS may therefore contribute to the diversity of dystroglycan function in the CNS, as well as to the broad clinical spectrum of type II lissencephalies. PMID:20980614

  7. Affect and the Brain's Functional Organization: A Resting-State Connectivity Approach

    PubMed Central

    Rohr, Christiane S.; Okon-Singer, Hadas; Craddock, R. Cameron; Villringer, Arno; Margulies, Daniel S.

    2013-01-01

    The question of how affective processing is organized in the brain is still a matter of controversial discussions. Based on previous initial evidence, several suggestions have been put forward regarding the involved brain areas: (a) right-lateralized dominance in emotional processing, (b) hemispheric dominance according to positive or negative valence, (c) one network for all emotional processing and (d) region-specific discrete emotion matching. We examined these hypotheses by investigating intrinsic functional connectivity patterns that covary with results of the Positive and Negative Affective Schedule (PANAS) from 65 participants. This approach has the advantage of being able to test connectivity rather than activation, and not requiring a potentially confounding task. Voxelwise functional connectivity from 200 regions-of-interest covering the whole brain was assessed. Positive and negative affect covaried with functional connectivity involving a shared set of regions, including the medial prefrontal cortex, the anterior cingulate, the visual cortex and the cerebellum. In addition, each affective domain had unique connectivity patterns, and the lateralization index showed a right hemispheric dominance for negative affect. Therefore, our results suggest a predominantly right-hemispheric network with affect-specific elements as the underlying organization of emotional processes. PMID:23935850

  8. Brain Structure and Executive Functions in Children with Cerebral Palsy: A Systematic Review

    ERIC Educational Resources Information Center

    Weierink, Lonneke; Vermeulen, R. Jeroen; Boyd, Roslyn N.

    2013-01-01

    This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using…

  9. Some Problems for Representations of Brain Organization Based on Activation in Functional Imaging

    ERIC Educational Resources Information Center

    Sidtis, John J.

    2007-01-01

    Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of…

  10. Brain Structure and Executive Functions in Children with Cerebral Palsy: A Systematic Review

    ERIC Educational Resources Information Center

    Weierink, Lonneke; Vermeulen, R. Jeroen; Boyd, Roslyn N.

    2013-01-01

    This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using

  11. Targeting brain tumor cAMP: the case for sex-specific therapeutics

    PubMed Central

    Warrington, Nicole M.; Sun, Tao; Rubin, Joshua B.

    2015-01-01

    A relationship between cyclic adenosine 3?, 5?-monophosphate (cAMP) levels and brain tumor biology has been evident for nearly as long as cAMP and its synthetase, adenylate cyclase (ADCY) have been known. The importance of the pathway in brain tumorigenesis has been demonstrated in vitro and in multiple animal models. Recently, we provided human validation for a cooperating oncogenic role for cAMP in brain tumorigenesis when we found that SNPs in ADCY8 were correlated with glioma (brain tumor) risk in individuals with Neurofibromatosis type 1 (NF1). Together, these studies provide a strong rationale for targeting cAMP in brain tumor therapy. However, the cAMP pathway is well-known to be sexually dimorphic, and SNPs in ADCY8 affected glioma risk in a sex-specific fashion, elevating the risk for females while protecting males. The cAMP pathway can be targeted at multiple levels in the regulation of its synthesis and degradation. Sex differences in response to drugs that target cAMP regulators indicate that successful targeting of the cAMP pathway for brain tumor patients is likely to require matching specific mechanisms of drug action with patient sex. PMID:26283963

  12. Self-regulation of circumscribed brain activity modulates spatially selective and frequency specific connectivity of distributed resting state networks

    PubMed Central

    Vukelić, Mathias; Gharabaghi, Alireza

    2015-01-01

    The mechanisms of learning involved in brain self-regulation have still to be unveiled to exploit the full potential of this methodology for therapeutic interventions. This skill of volitionally changing brain activity presumably resembles motor skill learning which in turn is accompanied by plastic changes modulating resting state networks. Along these lines, we hypothesized that brain regulation and neurofeedback would similarly modify intrinsic networks at rest while presenting a distinct spatio-temporal pattern. High-resolution electroencephalography preceded and followed a single neurofeedback training intervention of modulating circumscribed sensorimotor low β-activity by kinesthetic motor imagery in eleven healthy participants. The participants were kept in the deliberative phase of skill acquisition with high demands for learning self-regulation through stepwise increases of task difficulty. By applying the corrected imaginary part of the coherency function, we observed increased functional connectivity of both the primary motor and the primary somatosensory cortex with their respective contralateral homologous cortices in the low β-frequency band which was self-regulated during feedback. At the same time, the primary motor cortex—but none of the surrounding cortical areas—showed connectivity to contralateral supplementary motor and dorsal premotor areas in the high β-band. Simultaneously, the neurofeedback target displayed a specific increase of functional connectivity with an ipsilateral fronto-parietal network in the α-band while presenting a de-coupling with contralateral primary and secondary sensorimotor areas in the very same frequency band. Brain self-regulation modifies resting state connections spatially selective to the neurofeedback target of the dominant hemisphere. These are anatomically distinct with regard to the cortico-cortical connectivity pattern and are functionally specific with regard to the time domain of coherent activity consistent with a Hebbian-like sharpening concept. PMID:26236207

  13. Self-regulation of circumscribed brain activity modulates spatially selective and frequency specific connectivity of distributed resting state networks.

    PubMed

    Vukelić, Mathias; Gharabaghi, Alireza

    2015-01-01

    The mechanisms of learning involved in brain self-regulation have still to be unveiled to exploit the full potential of this methodology for therapeutic interventions. This skill of volitionally changing brain activity presumably resembles motor skill learning which in turn is accompanied by plastic changes modulating resting state networks. Along these lines, we hypothesized that brain regulation and neurofeedback would similarly modify intrinsic networks at rest while presenting a distinct spatio-temporal pattern. High-resolution electroencephalography preceded and followed a single neurofeedback training intervention of modulating circumscribed sensorimotor low β-activity by kinesthetic motor imagery in eleven healthy participants. The participants were kept in the deliberative phase of skill acquisition with high demands for learning self-regulation through stepwise increases of task difficulty. By applying the corrected imaginary part of the coherency function, we observed increased functional connectivity of both the primary motor and the primary somatosensory cortex with their respective contralateral homologous cortices in the low β-frequency band which was self-regulated during feedback. At the same time, the primary motor cortex-but none of the surrounding cortical areas-showed connectivity to contralateral supplementary motor and dorsal premotor areas in the high β-band. Simultaneously, the neurofeedback target displayed a specific increase of functional connectivity with an ipsilateral fronto-parietal network in the α-band while presenting a de-coupling with contralateral primary and secondary sensorimotor areas in the very same frequency band. Brain self-regulation modifies resting state connections spatially selective to the neurofeedback target of the dominant hemisphere. These are anatomically distinct with regard to the cortico-cortical connectivity pattern and are functionally specific with regard to the time domain of coherent activity consistent with a Hebbian-like sharpening concept. PMID:26236207

  14. 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 with BBS, which parallel the findings, described in BBS mutant mouse models. Some of these brain abnormalities may be progressive and associated with the reported neurological and behavioral problems. Further future correlation of these MRI scan findings with detailed neurologic and neuropsychological exams together with genotype data will provide better understanding of the pathophysiology of BBS. PMID:21794117

  15. Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.

    PubMed

    Karaca, Ender; Harel, Tamar; Pehlivan, Davut; Jhangiani, Shalini N; Gambin, Tomasz; Coban Akdemir, Zeynep; Gonzaga-Jauregui, Claudia; Erdin, Serkan; Bayram, Yavuz; Campbell, Ian M; Hunter, Jill V; Atik, Mehmed M; Van Esch, Hilde; Yuan, Bo; Wiszniewski, Wojciech; Isikay, Sedat; Yesil, Gozde; Yuregir, Ozge O; Tug Bozdogan, Sevcan; Aslan, Huseyin; Aydin, Hatip; Tos, Tulay; Aksoy, Ayse; De Vivo, Darryl C; Jain, Preti; Geckinli, B Bilge; Sezer, Ozlem; Gul, Davut; Durmaz, Burak; Cogulu, Ozgur; Ozkinay, Ferda; Topcu, Vehap; Candan, Sukru; Cebi, Alper Han; Ikbal, Mevlit; Yilmaz Gulec, Elif; Gezdirici, Alper; Koparir, Erkan; Ekici, Fatma; Coskun, Salih; Cicek, Salih; Karaer, Kadri; Koparir, Asuman; Duz, Mehmet Bugrahan; Kirat, Emre; Fenercioglu, Elif; Ulucan, Hakan; Seven, Mehmet; Guran, Tulay; Elcioglu, Nursel; Yildirim, Mahmut Selman; Aktas, Dilek; Alikaşifoğlu, Mehmet; Ture, Mehmet; Yakut, Tahsin; Overton, John D; Yuksel, Adnan; Ozen, Mustafa; Muzny, Donna M; Adams, David R; Boerwinkle, Eric; Chung, Wendy K; Gibbs, Richard A; Lupski, James R

    2015-11-01

    Development of the human nervous system involves complex interactions among fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate