WorldWideScience

Sample records for brain-specific neural zinc

  1. Cytosolic labile zinc: a marker for apoptosis in the developing rat brain.

    Science.gov (United States)

    Lee, Joo-Yong; Hwang, Jung Jin; Park, Mi-Ha; Koh, Jae-Young

    2006-01-01

    Cytosolic zinc accumulation was thought to occur specifically in neuronal death (necrosis) following acute injury. However, a recent study demonstrated that zinc accumulation also occurs in adult rat neurons undergoing apoptosis following target ablation, and in vitro experiments have shown that zinc accumulation may play a causal role in various forms of apoptosis. Here, we examined whether intraneuronal zinc accumulation occurs in central neurons undergoing apoptosis during development. Embryonic and newborn Sprague-Dawley rat brains were double-stained for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL) detection of apoptosis and immunohistochemical detection of stage-specific neuronal markers, such as nestin, proliferating cell nuclear antigen (PCNA), TuJ1 and neuronal nuclear specific protein (NeuN). The results revealed that apoptotic cell death occurred in neurons of diverse stages (neural stem cells, and dividing, young and adult neurons) throughout the brain during the embryonic and early postnatal periods. Further staining of brain sections with acid fuchsin or zinc-specific fluorescent dyes showed that all of the apoptotic neurons were acidophilic and contained labile zinc in their cell bodies. Cytosolic zinc accumulation was also observed in cultured cortical neurons undergoing staurosporine- or sodium nitroprusside (SNP)-induced apoptosis. In contrast, zinc chelation with CaEDTA or N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) reduced SNP-induced apoptosis but not staurosporine-induced apoptosis, indicating that cytosolic zinc accumulation does not play a causal role in all forms of apoptosis. Finally, the specific cytosolic zinc accumulation may have a practical application as a relatively simple marker for neurons undergoing developmental apoptosis.

  2. Zinc movement in the brain under kainate-induced seizures.

    Science.gov (United States)

    Takeda, Atsushi; Hirate, Maki; Tamano, Haruna; Oku, Naoto

    2003-05-01

    On the basis of the evidence that elimination of 65Zn from the brain of epilepsy (EL) mice is facilitated by induction of seizures, zinc movement in the brain was studied in mice injected with kainate (12 mg/kg x 3), which exhibited status epilepticus within 120 min after the last injection of kainate. Zinc concentrations in the brain were determined 24 h after the last injection of kainate. Zinc concentrations in the hippocampus, amygdala and cerebral cortex, in which zinc-containing glutamatergic neuron terminals exist, were significantly decreased by the treatment with kainate, while that in the cerebellum was not decreased. Timm's stain in the brain was extensively attenuated 24 h after the last injection of kainate. These results indicate that zinc homeostasis in the brain is affected by kainate-induced seizures. In the hippocampus of rats injected with kainate (10 mg/kg), furthermore, the release of zinc and glutamate into the extracellular fluid was studied using in vivo microdialysis. The levels of zinc and glutamate in the perfusate were increased along with seizure severity after injection of kainate. It is likely that zinc concentration in the synaptic vesicles is decreased by the excess excitation of glutamatergic neurons. The present study suggests that the excessive release of zinc and glutamate from the neuron terminals under kainate-induced seizures is associated with the loss of zinc from the brain.

  3. Influence of histidine on zinc transport into rat brain

    International Nuclear Information System (INIS)

    Takeda, Atsushi; Suzuki, Mai; Okada, Shoji; Oku, Naoto

    2000-01-01

    The brain of rats injected intravenously with 65 Zn-His or 65 ZnCl 2 was subjected to autoradiography to study the role of histidine on zinc transport into the brain. One hour after injection, the radioactivity from 65 Zn-His was largely concentrated in the choroid plexus in the ventricles. Six days after injection, the radioactivity from 65 Zn-His was relatively concentrated in the hippocampal CA3 and dentate gyrus and the amygdala. The relative distribution of 65 Zn-His in the brain was similar to that of 65 ZnCl 2 group at both 1 h and 6 days, suggesting that histidine may participate in zinc uptake in the brain. On the other hand, the clearance of the 65 Zn-His group from the blood was higher than that of the 65 ZnCl 2 group. Brain uptake of the former was lower than that of the latter both 1 h and 6 days after injection. These results suggest that zinc uptake in the brain is influenced by histidine levels in the bloodstream. (author)

  4. Perinatal ω-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood

    Science.gov (United States)

    Jayasooriya, Anura P.; Ackland, M. Leigh; Mathai, Michael L.; Sinclair, Andrew J.; Weisinger, Harrison S.; Weisinger, Richard S.; Halver, John E.; Kitajka, Klára; Puskás, László G.

    2005-01-01

    Dietary ω-3 polyunsaturated fatty acid (PUFA) influences the expression of a number of genes in the brain. Zinc transporter (ZnT) 3 has been identified as a putative transporter of zinc into synaptic vesicles of neurons and is found in brain areas such as hippocampus and cortex. Neuronal zinc is involved in the formation of amyloid plaques, a major characteristic of Alzheimer's disease. The present study evaluated the influence of dietary ω-3 PUFA on the expression of the ZnT3 gene in the brains of adult male Sprague-Dawley rats. The rats were raised and/or maintained on a control (CON) diet that contained ω-3 PUFA or a diet deficient (DEF) in ω-3 PUFA. ZnT3 gene expression was analyzed by using real-time PCR, free zinc in brain tissue was determined by zinquin staining, and total zinc concentrations in plasma and cerebrospinal fluid were determined by atomic absorption spectrophotometry. Compared with CON-raised animals, DEF-raised animals had increased expression of ZnT3 in the brain that was associated with an increased level of free zinc in the hippocampus. In addition, compared with CON-raised animals, DEF-raised animals had decreased plasma zinc level. No difference in cerebrospinal fluid zinc level was observed. The results suggest that overexpression of ZnT3 due to a perinatal ω-3 PUFA deficiency caused abnormal zinc metabolism in the brain. Conceivably, the influence of dietary ω-3 PUFA on brain zinc metabolism could explain the observation made in population studies that the consumption of fish is associated with a reduced risk of dementia and Alzheimer's disease. PMID:15883362

  5. Perinatal omega-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood.

    Science.gov (United States)

    Jayasooriya, Anura P; Ackland, M Leigh; Mathai, Michael L; Sinclair, Andrew J; Weisinger, Harrison S; Weisinger, Richard S; Halver, John E; Kitajka, Klára; Puskás, László G

    2005-05-17

    Dietary omega-3 polyunsaturated fatty acid (PUFA) influences the expression of a number of genes in the brain. Zinc transporter (ZnT) 3 has been identified as a putative transporter of zinc into synaptic vesicles of neurons and is found in brain areas such as hippocampus and cortex. Neuronal zinc is involved in the formation of amyloid plaques, a major characteristic of Alzheimer's disease. The present study evaluated the influence of dietary omega-3 PUFA on the expression of the ZnT3 gene in the brains of adult male Sprague-Dawley rats. The rats were raised and/or maintained on a control (CON) diet that contained omega-3 PUFA or a diet deficient (DEF) in omega-3 PUFA. ZnT3 gene expression was analyzed by using real-time PCR, free zinc in brain tissue was determined by zinquin staining, and total zinc concentrations in plasma and cerebrospinal fluid were determined by atomic absorption spectrophotometry. Compared with CON-raised animals, DEF-raised animals had increased expression of ZnT3 in the brain that was associated with an increased level of free zinc in the hippocampus. In addition, compared with CON-raised animals, DEF-raised animals had decreased plasma zinc level. No difference in cerebrospinal fluid zinc level was observed. The results suggest that overexpression of ZnT3 due to a perinatal omega-3 PUFA deficiency caused abnormal zinc metabolism in the brain. Conceivably, the influence of dietary omega-3 PUFA on brain zinc metabolism could explain the observation made in population studies that the consumption of fish is associated with a reduced risk of dementia and Alzheimer's disease.

  6. Influence of histidine on zinc transport into rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Atsushi; Suzuki, Mai; Okada, Shoji; Oku, Naoto [Shizuoka Univ. (Japan). School of Pharmaceutical Sciences

    2000-06-01

    The brain of rats injected intravenously with {sup 65}Zn-His or {sup 65}ZnCl{sub 2} was subjected to autoradiography to study the role of histidine on zinc transport into the brain. One hour after injection, the radioactivity from {sup 65}Zn-His was largely concentrated in the choroid plexus in the ventricles. Six days after injection, the radioactivity from {sup 65}Zn-His was relatively concentrated in the hippocampal CA3 and dentate gyrus and the amygdala. The relative distribution of {sup 65}Zn-His in the brain was similar to that of {sup 65}ZnCl{sub 2} group at both 1 h and 6 days, suggesting that histidine may participate in zinc uptake in the brain. On the other hand, the clearance of the {sup 65}Zn-His group from the blood was higher than that of the {sup 65}ZnCl{sub 2} group. Brain uptake of the former was lower than that of the latter both 1 h and 6 days after injection. These results suggest that zinc uptake in the brain is influenced by histidine levels in the bloodstream. (author)

  7. Brain Lateralization in Mice Is Associated with Zinc Signaling and Altered in Prenatal Zinc Deficient Mice That Display Features of Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Stefanie Grabrucker

    2018-01-01

    Full Text Available A number of studies have reported changes in the hemispheric dominance in autism spectrum disorder (ASD patients on functional, biochemical, and morphological level. Since asymmetry of the brain is also found in many vertebrates, we analyzed whether prenatal zinc deficient (PZD mice, a mouse model with ASD like behavior, show alterations regarding brain lateralization on molecular and behavioral level. Our results show that hemisphere-specific expression of marker genes is abolished in PZD mice on mRNA and protein level. Using magnetic resonance imaging, we found an increased striatal volume in PZD mice with no change in total brain volume. Moreover, behavioral patterns associated with striatal lateralization are altered and the lateralized expression of dopamine receptor 1 (DR1 in the striatum of PZD mice was changed. We conclude that zinc signaling during brain development has a critical role in the establishment of brain lateralization in mice.

  8. Release of zinc from the brain of El (epilepsy) mice during seizure induction.

    Science.gov (United States)

    Takeda, A; Hanajima, T; Ijiro, H; Ishige, A; Iizuka, S; Okada, S; Oku, N

    1999-05-15

    Brain distribution after i.v. injection of 65ZnCl2 into El mice, an animal model of genetically determined epilepsy, was studied by autoradiography to study the utilization of zinc in the brain. The distribution of 65Zn in the brain of El mice 6 days after injection was almost the same as that of ddY (normal) mice, suggesting that the uptake of zinc by the brain of El mice is normal. To study the movement of zinc in the brain in the course of seizure induction, the concentrations of 65Zn in the brain of seizure-afflicted and untreated control El mice were compared 20 days after 65Zn injection. The concentration of 65Zn in the brain of seized El mice was overall lower than that of control El mice; the concentration of 65Zn was decreased notably in the piriform cortex and amygdaloid nuclei complex during convulsion. These results suggest that the release of zinc from the El mouse brain is enhanced during convulsion. The decrease in actively functioning zinc in the brain may be associated with the increase in susceptibility to seizure in the El mouse. Copyright 1999 Elsevier Science B.V.

  9. Is Neural Activity Detected by ERP-Based Brain-Computer Interfaces Task Specific?

    Directory of Open Access Journals (Sweden)

    Markus A Wenzel

    Full Text Available Brain-computer interfaces (BCIs that are based on event-related potentials (ERPs can estimate to which stimulus a user pays particular attention. In typical BCIs, the user silently counts the selected stimulus (which is repeatedly presented among other stimuli in order to focus the attention. The stimulus of interest is then inferred from the electroencephalogram (EEG. Detecting attention allocation implicitly could be also beneficial for human-computer interaction (HCI, because it would allow software to adapt to the user's interest. However, a counting task would be inappropriate for the envisaged implicit application in HCI. Therefore, the question was addressed if the detectable neural activity is specific for silent counting, or if it can be evoked also by other tasks that direct the attention to certain stimuli.Thirteen people performed a silent counting, an arithmetic and a memory task. The tasks required the subjects to pay particular attention to target stimuli of a random color. The stimulus presentation was the same in all three tasks, which allowed a direct comparison of the experimental conditions.Classifiers that were trained to detect the targets in one task, according to patterns present in the EEG signal, could detect targets in all other tasks (irrespective of some task-related differences in the EEG.The neural activity detected by the classifiers is not strictly task specific but can be generalized over tasks and is presumably a result of the attention allocation or of the augmented workload. The results may hold promise for the transfer of classification algorithms from BCI research to implicit relevance detection in HCI.

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

    Science.gov (United States)

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-21

    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.

  11. Radioisotopic investigations of zinc uptake into brain slices

    International Nuclear Information System (INIS)

    Howell, G.A.

    1983-01-01

    The presence of zinc in the vicinity of the hippocampal mossy fibers has been repeatedly demonstrated, and several lines of evidence suggest that the mossy-fiber zinc is concentrated within the terminals of mossy fibers. In search of insight into the metabolism and function of mossy-fiber zinc, the present study investigated the transport of zinc into tissue slices and the response of the zinc transport to depolarization. Kinetic analysis of zinc accumulation by mouse brain slices in vitro revealed the presence of a high affinity uptake component with an apparent Km of 17.7 μM for hippocampus, 16.6 μM< for cortex and 25 μM for striatum and a V/sub max/ of 9.2 ng/mg/hr for the hippocampus, 10.1 ng/mg/hr for cortex and 9.6 ng/mg/hr for striatum. Cytoarchitectonic differences in zinc transport between the different hippocampal subregions were found with those regions containing granule cells or mossy fiber axons accumulating greater amounts of zinc than the CA 1 region. The present finding that mossy-fiber neuropil selectivity accumulates zinc suggests the presence of a zinc-binding substance unique to mossy-fiber tissue

  12. Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development

    Directory of Open Access Journals (Sweden)

    Bello Bruno C

    2008-02-01

    Full Text Available Abstract Background In the mammalian brain, neural stem cells divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. Here we investigate whether specific neural stem cell-like neuroblasts in the brain of Drosophila might also amplify neuronal proliferation by generating symmetrically dividing intermediate progenitors. Results Cell lineage-tracing and genetic marker analysis show that remarkably large neuroblast lineages exist in the dorsomedial larval brain of Drosophila. These lineages are generated by brain neuroblasts that divide asymmetrically to self renew but, unlike other brain neuroblasts, do not segregate the differentiating cell fate determinant Prospero to their smaller daughter cells. These daughter cells continue to express neuroblast-specific molecular markers and divide repeatedly to produce neural progeny, demonstrating that they are proliferating intermediate progenitors. The proliferative divisions of these intermediate progenitors have novel cellular and molecular features; they are morphologically symmetrical, but molecularly asymmetrical in that key differentiating cell fate determinants are segregated into only one of the two daughter cells. Conclusion Our findings provide cellular and molecular evidence for a new mode of neurogenesis in the larval brain of Drosophila that involves the amplification of neuroblast proliferation through intermediate progenitors. This type of neurogenesis bears remarkable similarities to neurogenesis in the mammalian brain, where neural stem cells as primary progenitors amplify the number of progeny they generate through generation of secondary progenitors. This suggests that key aspects of neural stem cell biology might be conserved in brain development of insects and mammals.

  13. Neural decoding of collective wisdom with multi-brain computing.

    Science.gov (United States)

    Eckstein, Miguel P; Das, Koel; Pham, Binh T; Peterson, Matthew F; Abbey, Craig K; Sy, Jocelyn L; Giesbrecht, Barry

    2012-01-02

    Group decisions and even aggregation of multiple opinions lead to greater decision accuracy, a phenomenon known as collective wisdom. Little is known about the neural basis of collective wisdom and whether its benefits arise in late decision stages or in early sensory coding. Here, we use electroencephalography and multi-brain computing with twenty humans making perceptual decisions to show that combining neural activity across brains increases decision accuracy paralleling the improvements shown by aggregating the observers' opinions. Although the largest gains result from an optimal linear combination of neural decision variables across brains, a simpler neural majority decision rule, ubiquitous in human behavior, results in substantial benefits. In contrast, an extreme neural response rule, akin to a group following the most extreme opinion, results in the least improvement with group size. Analyses controlling for number of electrodes and time-points while increasing number of brains demonstrate unique benefits arising from integrating neural activity across different brains. The benefits of multi-brain integration are present in neural activity as early as 200 ms after stimulus presentation in lateral occipital sites and no additional benefits arise in decision related neural activity. Sensory-related neural activity can predict collective choices reached by aggregating individual opinions, voting results, and decision confidence as accurately as neural activity related to decision components. Estimation of the potential for the collective to execute fast decisions by combining information across numerous brains, a strategy prevalent in many animals, shows large time-savings. Together, the findings suggest that for perceptual decisions the neural activity supporting collective wisdom and decisions arises in early sensory stages and that many properties of collective cognition are explainable by the neural coding of information across multiple brains. Finally

  14. Zinc in Gut-Brain Interaction in Autism and Neurological Disorders

    Science.gov (United States)

    Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M.

    2015-01-01

    A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life. PMID:25878905

  15. Evidence for a zinc/proton antiporter in rat brain.

    Science.gov (United States)

    Colvin, R A; Davis, N; Nipper, R W; Carter, P A

    2000-05-01

    The data presented in this paper are consistent with the existence of a plasma membrane zinc/proton antiport activity in rat brain. Experiments were performed using purified plasma membrane vesicles isolated from whole rat brain. Incubating vesicles in the presence of various concentrations of 65Zn2+ resulted in a rapid accumulation of 65Zn2+. Hill plot analysis demonstrated a lack of cooperativity in zinc activation of 65Zn2+ uptake. Zinc uptake was inhibited in the presence of 1 mM Ni2+, Cd2+, or CO2+. Calcium (1 mM) was less effective at inhibiting 65Zn2+ uptake and Mg2+ and Mn2+ had no effect. The initial rate of vesicular 65Zn2+ uptake was inhibited by increasing extravesicular H+ concentration. Vesicles preloaded with 65Zn2+ could be induced to release 65Zn2+ by increasing extravesicular H+ or addition of 1 mM nonradioactive Zn2+. Hill plot analysis showed a lack of cooperativity in H+ activation of 65Zn2+ release. Based on the Hill analyses, the stoichiometry of transport may include Zn2+/Zn2+ exchange and Zn2+/H+ antiport, the latter being potentially electrogenic. Zinc/proton antiport may be an important mode of zinc uptake into neurons and contribute to the reuptake of zinc to replenish presynaptic vesicle stores after stimulation.

  16. Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

    Science.gov (United States)

    Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito; Ye, Peng; Shi, Yanhong

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.

  17. Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

    Science.gov (United States)

    Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

    2008-01-01

    TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

  18. Histochemical distribution of zinc in the brain of the rainbow trout, Oncorhynchos myciss. I. The telencephalon

    DEFF Research Database (Denmark)

    Piñuela, C; Baatrup, E; Geneser, F A

    1992-01-01

    was mainly confined to the neuropil, but both moderately and intensely stained nerve cell bodies were of common occurrence. Stained fibers were never observed. The staining revealed a specific distribution pattern which could easily be correlated with the telencephalic nuclei defined on the basis......The present paper which describes the distribution of zinc in the telencephalon of the rainbow trout, Oncorhynchos myciss, is the first report on the distribution of a heavy metal in the fish brain. Zinc was demonstrated histochemically by silver enhancement using the Neo-Timm method. The staining...... of cytoarchitectural features. However, the telencephalon stained much more weakly than the rest of the brain, in striking contrast to the situation in the reptilian, mammalian, and avian brain. In these classes, high staining intensities are observed almost exclusively in the telencephalon. The staining...

  19. Nuclear Receptor TLX Regulates Cell Cycle Progression in Neural Stem Cells of the Developing Brain

    OpenAIRE

    Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

    2007-01-01

    TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal ...

  20. Zinc finger protein 521 overexpression increased transcript levels of ...

    Indian Academy of Sciences (India)

    2016-02-12

    Feb 12, 2016 ... Zinc finger protein 521 is highly expressed in brain, neural stem cells and early progenitors of the human .... Membranes were blocked for 1 h with 10% skim milk and ..... fat-like development of white fat and thermogenesis.

  1. Using Brain Stimulation to Disentangle Neural Correlates of Conscious Vision

    Directory of Open Access Journals (Sweden)

    Tom Alexander de Graaf

    2014-09-01

    Full Text Available Research into the neural correlates of consciousness (NCCs has blossomed, due to the advent of new and increasingly sophisticated brain research tools. Neuroimaging has uncovered a variety of brain processes that relate to conscious perception, obtained in a range of experimental paradigms. But methods such as fMRI or EEG do not always afford inference on the role these brain processes play in conscious vision. Such empirical neural correlates of consciousness could reflect neural prerequisites, neural consequences, or neural substrates of a conscious experience. Here, we take a closer look at the use of non-invasive brain stimulation (NIBS techniques in this context. We discuss and review how NIBS methodology can enlighten our understanding of brain mechanisms underlying conscious vision by disentangling the empirical neural correlates of consciousness.

  2. High Frequency Deep Brain Stimulation and Neural Rhythms in Parkinson's Disease.

    Science.gov (United States)

    Blumenfeld, Zack; Brontë-Stewart, Helen

    2015-12-01

    High frequency (HF) deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease (PD). It effectively treats the cardinal motor signs of PD, including tremor, bradykinesia, and rigidity. The most common neural target is the subthalamic nucleus, located within the basal ganglia, the region most acutely affected by PD pathology. Using chronically-implanted DBS electrodes, researchers have been able to record underlying neural rhythms from several nodes in the PD network as well as perturb it using DBS to measure the ensuing neural and behavioral effects, both acutely and over time. In this review, we provide an overview of the PD neural network, focusing on the pathophysiological signals that have been recorded from PD patients as well as the mechanisms underlying the therapeutic benefits of HF DBS. We then discuss evidence for the relationship between specific neural oscillations and symptoms of PD, including the aberrant relationships potentially underlying functional connectivity in PD as well as the use of different frequencies of stimulation to more specifically target certain symptoms. Finally, we briefly describe several current areas of investigation and how the ability to record neural data in ecologically-valid settings may allow researchers to explore the relationship between brain and behavior in an unprecedented manner, culminating in the future automation of neurostimulation therapy for the treatment of a variety of neuropsychiatric diseases.

  3. Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

    Directory of Open Access Journals (Sweden)

    Shengxiu Li

    Full Text Available TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.

  4. Electrical brain responses in language-impaired children reveal grammar-specific deficits.

    Directory of Open Access Journals (Sweden)

    Elisabeth Fonteneau

    2008-03-01

    Full Text Available Scientific and public fascination with human language have included intensive scrutiny of language disorders as a new window onto the biological foundations of language and its evolutionary origins. Specific language impairment (SLI, which affects over 7% of children, is one such disorder. SLI has received robust scientific attention, in part because of its recent linkage to a specific gene and loci on chromosomes and in part because of the prevailing question regarding the scope of its language impairment: Does the disorder impact the general ability to segment and process language or a specific ability to compute grammar? Here we provide novel electrophysiological data showing a domain-specific deficit within the grammar of language that has been hitherto undetectable through behavioural data alone.We presented participants with Grammatical(G-SLI, age-matched controls, and younger child and adult controls, with questions containing syntactic violations and sentences containing semantic violations. Electrophysiological brain responses revealed a selective impairment to only neural circuitry that is specific to grammatical processing in G-SLI. Furthermore, the participants with G-SLI appeared to be partially compensating for their syntactic deficit by using neural circuitry associated with semantic processing and all non-grammar-specific and low-level auditory neural responses were normal.The findings indicate that grammatical neural circuitry underlying language is a developmentally unique system in the functional architecture of the brain, and this complex higher cognitive system can be selectively impaired. The findings advance fundamental understanding about how cognitive systems develop and all human language is represented and processed in the brain.

  5. Neural Plastic Effects of Cognitive Training on Aging Brain

    Directory of Open Access Journals (Sweden)

    Natalie T. Y. Leung

    2015-01-01

    Full Text Available Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n=109 and the Active Control Group (n=100. Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

  6. Neural Plastic Effects of Cognitive Training on Aging Brain.

    Science.gov (United States)

    Leung, Natalie T Y; Tam, Helena M K; Chu, Leung W; Kwok, Timothy C Y; Chan, Felix; Lam, Linda C W; Woo, Jean; Lee, Tatia M C

    2015-01-01

    Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age.

  7. The potential of neural transplantation for brain repair and regeneration following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dong Sun

    2016-01-01

    Traumatic brain injury is a major health problem worldwide. Currently, there is no effective treatment to improve neural structural repair and functional recovery of patients in the clinic. Cell transplantation is a potential strategy to repair and regenerate the injured brain. This review article summarized recent de-velopment in cell transplantation studies for post-traumatic brain injury brain repair with varying types of cell sources. It also discussed the potential of neural transplantation to repair/promote recovery of the injured brain following traumatic brain injury.

  8. Using brain stimulation to disentangle neural correlates of conscious vision.

    Science.gov (United States)

    de Graaf, Tom A; Sack, Alexander T

    2014-01-01

    Research into the neural correlates of consciousness (NCCs) has blossomed, due to the advent of new and increasingly sophisticated brain research tools. Neuroimaging has uncovered a variety of brain processes that relate to conscious perception, obtained in a range of experimental paradigms. But methods such as functional magnetic resonance imaging or electroencephalography do not always afford inference on the functional role these brain processes play in conscious vision. Such empirical NCCs could reflect neural prerequisites, neural consequences, or neural substrates of a conscious experience. Here, we take a closer look at the use of non-invasive brain stimulation (NIBS) techniques in this context. We discuss and review how NIBS methodology can enlighten our understanding of brain mechanisms underlying conscious vision by disentangling the empirical NCCs.

  9. Zinc and glutamate dehydrogenase in putative glutamatergic brain structures.

    Science.gov (United States)

    Wolf, G; Schmidt, W

    1983-01-01

    A certain topographic parallelism between the distribution of histochemically (TIMM staining) identified zinc and putative glutamatergic structures in the rat brain was demonstrated. Glutamate dehydrogenase as a zinc containing protein is in consideration to be an enzyme synthesizing transmitter glutamate. In a low concentration range externally added zinc ions (10(-9) to 10(-7) M) induced an increase in the activity of glutamate dehydrogenase (GDH) originating from rat hippocampal formation, neocortex, and cerebellum up to 142.4%. With rising molarity of Zn(II) in the incubation medium, the enzyme of hippocampal formation and cerebellum showed a biphasic course of activation. Zinc ions of a concentration higher than 10(-6) M caused a strong inhibition of GDH. The effect of Zn(II) on GDH originating from spinal ganglia and liver led only to a decrease of enzyme activity. These results are discussed in connection with a functional correlation between zinc and putatively glutamatergic system.

  10. Neural markers of loss aversion in resting-state brain activity.

    Science.gov (United States)

    Canessa, Nicola; Crespi, Chiara; Baud-Bovy, Gabriel; Dodich, Alessandra; Falini, Andrea; Antonellis, Giulia; Cappa, Stefano F

    2017-02-01

    Neural responses in striatal, limbic and somatosensory brain regions track individual differences in loss aversion, i.e. the higher sensitivity to potential losses compared with equivalent gains in decision-making under risk. The engagement of structures involved in the processing of aversive stimuli and experiences raises a further question, i.e. whether the tendency to avoid losses rather than acquire gains represents a transient fearful overreaction elicited by choice-related information, or rather a stable component of one's own preference function, reflecting a specific pattern of neural activity. We tested the latter hypothesis by assessing in 57 healthy human subjects whether the relationship between behavioral and neural loss aversion holds at rest, i.e. when the BOLD signal is collected during 5minutes of cross-fixation in the absence of an explicit task. Within the resting-state networks highlighted by a spatial group Independent Component Analysis (gICA), we found a significant correlation between strength of activity and behavioral loss aversion in the left ventral striatum and right posterior insula/supramarginal gyrus, i.e. the very same regions displaying a pattern of neural loss aversion during explicit choices. Cross-study analyses confirmed that this correlation holds when voxels identified by gICA are used as regions of interest in task-related activity and vice versa. These results suggest that the individual degree of (neural) loss aversion represents a stable dimension of decision-making, which reflects in specific metrics of intrinsic brain activity at rest possibly modulating cortical excitability at choice. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor

    Directory of Open Access Journals (Sweden)

    Ebrahim Shahbazi

    2016-04-01

    Full Text Available Direct conversion of somatic cells into neural stem cells (NSCs by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. In addition, the single-seeded induced NSCs were able to form NSC colonies with efficiency comparable with control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating, and attaining neural phenotypes after transplantation into neonatal mouse and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts.

  12. Brain noise is task dependent and region specific.

    Science.gov (United States)

    Misić, Bratislav; Mills, Travis; Taylor, Margot J; McIntosh, Anthony R

    2010-11-01

    The emerging organization of anatomical and functional connections during human brain development is thought to facilitate global integration of information. Recent empirical and computational studies have shown that this enhanced capacity for information processing enables a diversified dynamic repertoire that manifests in neural activity as irregularity and noise. However, transient functional networks unfold over multiple time, scales and the embedding of a particular region depends not only on development, but also on the manner in which sensory and cognitive systems are engaged. Here we show that noise is a facet of neural activity that is also sensitive to the task context and is highly region specific. Children (6-16 yr) and adults (20-41 yr) performed a one-back face recognition task with inverted and upright faces. Neuromagnetic activity was estimated at several hundred sources in the brain by applying a beamforming technique to the magnetoencephalogram (MEG). During development, neural activity became more variable across the whole brain, with most robust increases in medial parietal regions, such as the precuneus and posterior cingulate cortex. For young children and adults, activity evoked by upright faces was more variable and noisy compared with inverted faces, and this effect was reliable only in the right fusiform gyrus. These results are consistent with the notion that upright faces engender a variety of integrative neural computations, such as the relations among facial features and their holistic constitution. This study shows that transient changes in functional integration modulated by task demand are evident in the variability of regional neural activity.

  13. Neural substrate expansion for the restoration of brain function

    Directory of Open Access Journals (Sweden)

    Han-Chiao Isaac Chen

    2016-01-01

    Full Text Available 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.

  14. Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

    Science.gov (United States)

    Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

    2017-10-13

    The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

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

    Directory of Open Access Journals (Sweden)

    Jian-Ying Chuang

    2017-04-01

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

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

    Science.gov (United States)

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

    2018-03-01

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

  17. Neural Plasticity and Neurorehabilitation: Teaching the New Brain Old Tricks

    Science.gov (United States)

    Kleim, Jeffrey A.

    2011-01-01

    Following brain injury or disease there are widespread biochemical, anatomical and physiological changes that result in what might be considered a new, very different brain. This adapted brain is forced to reacquire behaviors lost as a result of the injury or disease and relies on neural plasticity within the residual neural circuits. The same…

  18. Dynamic Neural State Identification in Deep Brain Local Field Potentials of Neuropathic Pain.

    Science.gov (United States)

    Luo, Huichun; Huang, Yongzhi; Du, Xueying; Zhang, Yunpeng; Green, Alexander L; Aziz, Tipu Z; Wang, Shouyan

    2018-01-01

    In neuropathic pain, the neurophysiological and neuropathological function of the ventro-posterolateral nucleus of the thalamus (VPL) and the periventricular gray/periaqueductal gray area (PVAG) involves multiple frequency oscillations. Moreover, oscillations related to pain perception and modulation change dynamically over time. Fluctuations in these neural oscillations reflect the dynamic neural states of the nucleus. In this study, an approach to classifying the synchronization level was developed to dynamically identify the neural states. An oscillation extraction model based on windowed wavelet packet transform was designed to characterize the activity level of oscillations. The wavelet packet coefficients sparsely represented the activity level of theta and alpha oscillations in local field potentials (LFPs). Then, a state discrimination model was designed to calculate an adaptive threshold to determine the activity level of oscillations. Finally, the neural state was represented by the activity levels of both theta and alpha oscillations. The relationship between neural states and pain relief was further evaluated. The performance of the state identification approach achieved sensitivity and specificity beyond 80% in simulation signals. Neural states of the PVAG and VPL were dynamically identified from LFPs of neuropathic pain patients. The occurrence of neural states based on theta and alpha oscillations were correlated to the degree of pain relief by deep brain stimulation. In the PVAG LFPs, the occurrence of the state with high activity levels of theta oscillations independent of alpha and the state with low-level alpha and high-level theta oscillations were significantly correlated with pain relief by deep brain stimulation. This study provides a reliable approach to identifying the dynamic neural states in LFPs with a low signal-to-noise ratio by using sparse representation based on wavelet packet transform. Furthermore, it may advance closed-loop deep

  19. Construction and application of a zinc-specific biosensor for assessing the immobilization and bioavailability of zinc in different soils

    International Nuclear Information System (INIS)

    Liu Pulin; Huang Qiaoyun; Chen Wenli

    2012-01-01

    The inducibility and specificity of different czcRS operons in Pseudomonas putida X4 were studied by lacZ gene fusions. The data of β-glycosidase activity confirmed that the czcR3 promoter responded quantitatively to zinc. A zinc-specific biosensor, P. putida X4 (pczcR3GFP), was constructed by fusing a promoterless enhanced green fluorescent protein (egfp) gene with the czcR3 promoter in the chromosome of P. putida X4. In water extracts of four different soils amended with zinc, the reporter strain detected about 90% of the zinc content of the samples. Both the bioavailability assessment and the sequential extraction analysis demonstrated that the immobilization of zinc was highly dependent on the physico-chemical properties of soils. The results also showed that the lability of zinc decreased over time. It is concluded that the biosensor constitutes an alternative system for the convenient evaluation of zinc toxicity in the environment. - Highlights: ► A zinc-specific bacterial biosensor was developed. ► Four spiked soils were used to test the application of this biosensor. ► The bioavailable zinc in soil-water extracts decreased due to aging. ► The immobilization and speciation of zinc were highly dependent on the soil type. - The immobilization and bioavailability of zinc in soil were investigated as a function of soil type and aging by a newly constructed zinc-specific biosensor coupled with chemical analysis.

  20. Stimulating at the right time: phase-specific deep brain stimulation.

    Science.gov (United States)

    Cagnan, Hayriye; Pedrosa, David; Little, Simon; Pogosyan, Alek; Cheeran, Binith; Aziz, Tipu; Green, Alexander; Fitzgerald, James; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Friston, Karl J; Denison, Timothy; Brown, Peter

    2017-01-01

    SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  1. Individual Identification Using Functional Brain Fingerprint Detected by Recurrent Neural Network.

    Science.gov (United States)

    Chen, Shiyang; Hu, Xiaoping P

    2018-03-20

    Individual identification based on brain function has gained traction in literature. Investigating individual differences in brain function can provide additional insights into the brain. In this work, we introduce a recurrent neural network based model for identifying individuals based on only a short segment of resting state functional MRI data. In addition, we demonstrate how the global signal and differences in atlases affect the individual identifiability. Furthermore, we investigate neural network features that exhibit the uniqueness of each individual. The results indicate that our model is able to identify individuals based on neural features and provides additional information regarding brain dynamics.

  2. Immersion autometallography: histochemical in situ capturing of zinc ions in catalytic zinc-sulfur nanocrystals.

    Science.gov (United States)

    Danscher, Gorm; Stoltenberg, Meredin; Bruhn, Mikkel; Søndergaard, Chris; Jensen, Dorete

    2004-12-01

    In the mid-1980s, two versions of Timm's original immersion sulfide silver method were published. The authors used immersion of tissue in a sulfide solution as opposed to Timm, who used immersion of tissue blocks in hydrogen sulfide-bubbled alcohol. The autometallography staining resulting from the "sulfide only immersion" was not particularly impressive, but the significance of this return to an old approach became obvious when Wenzel and co-workers presented their approach in connection with introduction by the Palmiter group of zinc transporter 3 (ZnT3). The Wenzel/Palmiter pictures are the first high-resolution, high-quality pictures taken from tissues in which free and loosely bound zinc ions have been captured in zinc-sulfur nanocrystals by immersion. The trick was to place formalin-fixed blocks of mouse brains in a solution containing 3% glutaraldehyde and 0.1% sodium sulfide, ingredients used for transcardial perfusion in the zinc-specific NeoTimm method. That the NeoTimm technique results in silver enhancement of zinc-sulfur nanocrystals has been proved by proton-induced X-ray multielement analyses (PIXE) and in vivo chelation with diethyldithiocarbamate (DEDTC). The aims of the present study were (a) to make the immersion-based capturing of zinc ions in zinc-sulfur nanocrystals work directly on sections and slices of fixed brain tissue, (b) to work out protocols that ensure zinc specificity and optimal quality of the staining, (c) to apply "immersion autometallography" (iZnSAMG) to other tissues that contain zinc-enriched (ZEN) cells, and (d) to make the immersion approach work on unfixed fresh tissue.

  3. Neural stem cells in the ischemic and injured brain: endogenous and transplanted.

    Science.gov (United States)

    Dong, Jing; Liu, Baohua; Song, Lei; Lu, Lei; Xu, Haitao; Gu, Yue

    2012-12-01

    Neural stem cells functions as the pool of new neurons in adult brain, and plays important roles in normal brain function. Additionally, this pool reacts to brain ischemia, hemorrhage, trauma and many kinds of diseases, serving as endogenous repair mechanisms. The present manuscript discussed the responses of adult neurogenesis to brain ischemia and other insults, then the potential of neural stem cell transplantation therapy to treat such brain injury conditions.

  4. Effect of zinc supplementation on neuronal precursor proliferation in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Cope, Elise C; Morris, Deborah R; Gower-Winter, Shannon D; Brownstein, Naomi C; Levenson, Cathy W

    2016-05-01

    There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (pprecursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Optimal Brain Surgeon on Artificial Neural Networks in

    DEFF Research Database (Denmark)

    Christiansen, Niels Hørbye; Job, Jonas Hultmann; Klyver, Katrine

    2012-01-01

    It is shown how the procedure know as optimal brain surgeon can be used to trim and optimize artificial neural networks in nonlinear structural dynamics. Beside optimizing the neural network, and thereby minimizing computational cost in simulation, the surgery procedure can also serve as a quick...

  6. The zinc dyshomeostasis hypothesis of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Travis J A Craddock

    Full Text Available Alzheimer's disease (AD is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ, intracellular neurofibrillary tangles (NFTs composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau, and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1 used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2 performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3 used metallomic imaging mass spectrometry (MIMS to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of

  7. The zinc dyshomeostasis hypothesis of Alzheimer's disease.

    Science.gov (United States)

    Craddock, Travis J A; Tuszynski, Jack A; Chopra, Deepak; Casey, Noel; Goldstein, Lee E; Hameroff, Stuart R; Tanzi, Rudolph E

    2012-01-01

    Alzheimer's disease (AD) is the most common form of dementia in the elderly. Hallmark AD neuropathology includes extracellular amyloid plaques composed largely of the amyloid-β protein (Aβ), intracellular neurofibrillary tangles (NFTs) composed of hyper-phosphorylated microtubule-associated protein tau (MAP-tau), and microtubule destabilization. Early-onset autosomal dominant AD genes are associated with excessive Aβ accumulation, however cognitive impairment best correlates with NFTs and disrupted microtubules. The mechanisms linking Aβ and NFT pathologies in AD are unknown. Here, we propose that sequestration of zinc by Aβ-amyloid deposits (Aβ oligomers and plaques) not only drives Aβ aggregation, but also disrupts zinc homeostasis in zinc-enriched brain regions important for memory and vulnerable to AD pathology, resulting in intra-neuronal zinc levels, which are either too low, or excessively high. To evaluate this hypothesis, we 1) used molecular modeling of zinc binding to the microtubule component protein tubulin, identifying specific, high-affinity zinc binding sites that influence side-to-side tubulin interaction, the sensitive link in microtubule polymerization and stability. We also 2) performed kinetic modeling showing zinc distribution in extra-neuronal Aβ deposits can reduce intra-neuronal zinc binding to microtubules, destabilizing microtubules. Finally, we 3) used metallomic imaging mass spectrometry (MIMS) to show anatomically-localized and age-dependent zinc dyshomeostasis in specific brain regions of Tg2576 transgenic, mice, a model for AD. We found excess zinc in brain regions associated with memory processing and NFT pathology. Overall, we present a theoretical framework and support for a new theory of AD linking extra-neuronal Aβ amyloid to intra-neuronal NFTs and cognitive dysfunction. The connection, we propose, is based on β-amyloid-induced alterations in zinc ion concentration inside neurons affecting stability of polymerized

  8. BrainNetCNN: Convolutional neural networks for brain networks; towards predicting neurodevelopment.

    Science.gov (United States)

    Kawahara, Jeremy; Brown, Colin J; Miller, Steven P; Booth, Brian G; Chau, Vann; Grunau, Ruth E; Zwicker, Jill G; Hamarneh, Ghassan

    2017-02-01

    We propose BrainNetCNN, a convolutional neural network (CNN) framework to predict clinical neurodevelopmental outcomes from brain networks. In contrast to the spatially local convolutions done in traditional image-based CNNs, our BrainNetCNN is composed of novel edge-to-edge, edge-to-node and node-to-graph convolutional filters that leverage the topological locality of structural brain networks. We apply the BrainNetCNN framework to predict cognitive and motor developmental outcome scores from structural brain networks of infants born preterm. Diffusion tensor images (DTI) of preterm infants, acquired between 27 and 46 weeks gestational age, were used to construct a dataset of structural brain connectivity networks. We first demonstrate the predictive capabilities of BrainNetCNN on synthetic phantom networks with simulated injury patterns and added noise. BrainNetCNN outperforms a fully connected neural-network with the same number of model parameters on both phantoms with focal and diffuse injury patterns. We then apply our method to the task of joint prediction of Bayley-III cognitive and motor scores, assessed at 18 months of age, adjusted for prematurity. We show that our BrainNetCNN framework outperforms a variety of other methods on the same data. Furthermore, BrainNetCNN is able to identify an infant's postmenstrual age to within about 2 weeks. Finally, we explore the high-level features learned by BrainNetCNN by visualizing the importance of each connection in the brain with respect to predicting the outcome scores. These findings are then discussed in the context of the anatomy and function of the developing preterm infant brain. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Nonlinear transfer function encodes synchronization in a neural network from the mammalian brain.

    Science.gov (United States)

    Menendez de la Prida, L; Sanchez-Andres, J V

    1999-09-01

    Synchronization is one of the mechanisms by which the brain encodes information. The observed synchronization of neuronal activity has, however, several levels of fluctuations, which presumably regulate local features of specific areas. This means that biological neural networks should have an intrinsic mechanism able to synchronize the neuronal activity but also to preserve the firing capability of individual cells. Here, we investigate the input-output relationship of a biological neural network from developing mammalian brain, i.e., the hippocampus. We show that the probability of occurrence of synchronous output activity (which consists in stereotyped population bursts recorded throughout the hippocampus) is encoded by a sigmoidal transfer function of the input frequency. Under this scope, low-frequency inputs will not produce any coherent output while high-frequency inputs will determine a synchronous pattern of output activity (population bursts). We analyze the effect of the network size (N) on the parameters of the transfer function (threshold and slope). We found that sigmoidal functions realistically simulate the synchronous output activity of hippocampal neural networks. This outcome is particularly important in the application of results from neural network models to neurobiology.

  10. Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool

    Directory of Open Access Journals (Sweden)

    Ksenija Zega

    2017-11-01

    Full Text Available Hydrocephalus can occur in children alone or in combination with other neurodevelopmental disorders that are often associated with brain overgrowth. Despite the severity of these disorders, the molecular and cellular mechanisms underlying these pathologies and their comorbidity are poorly understood. Here, we studied the consequences of genetically inactivating in mice dual-specificity phosphatase 16 (Dusp16, which is known to negatively regulate mitogen-activated protein kinases (MAPKs and which has never previously been implicated in brain development and disorders. Mouse mutants lacking a functional Dusp16 gene (Dusp16−/− developed fully-penetrant congenital obstructive hydrocephalus together with brain overgrowth. The midbrain aqueduct in Dusp16−/− mutants was obstructed during mid-gestation by an expansion of neural progenitors, and during later gestational stages by neurons resulting in a blockage of cerebrospinal fluid (CSF outflow. In contrast, the roof plate and ependymal cells developed normally. We identified a delayed cell cycle exit of neural progenitors in Dusp16−/− mutants as a cause of progenitor overproliferation during mid-gestation. At later gestational stages, this expanded neural progenitor pool generated an increased number of neurons associated with enlarged brain volume. Taken together, we found that Dusp16 plays a critical role in neurogenesis by balancing neural progenitor cell proliferation and neural differentiation. Moreover our results suggest that a lack of functional Dusp16 could play a central role in the molecular mechanisms linking brain overgrowth and hydrocephalus.

  11. Isointense infant brain MRI segmentation with a dilated convolutional neural network

    OpenAIRE

    Moeskops, Pim; Pluim, Josien P. W.

    2017-01-01

    Quantitative analysis of brain MRI at the age of 6 months is difficult because of the limited contrast between white matter and gray matter. In this study, we use a dilated triplanar convolutional neural network in combination with a non-dilated 3D convolutional neural network for the segmentation of white matter, gray matter and cerebrospinal fluid in infant brain MR images, as provided by the MICCAI grand challenge on 6-month infant brain MRI segmentation.

  12. Similar judgment method of brain neural pathway using DT-MRI

    International Nuclear Information System (INIS)

    Watashiba, Yasuhiro; Sakamoto, Naohisa; Sakai, Koji; Koyamada, Koji; Kanazawa, Masanori; Doi, Akio

    2008-01-01

    Nowadays, the visualization of brain neural pathway extracted by the tractography technology is thought as a useful effective tool for the detection of involved area and the analysis of sick cause by comparison of difference of normal and patient's nerve fiber configurations and for the support of the surgery planning and the forecast of progress after an operation. So far, for the observation of the brain neural pathway, the method of the user's subjectively judging the 3D shape of them displayed in the image has been used. However, in this kind of subjective observation, verification of the propriety for the diagnostic result is difficult, in addition it cannot obtain sufficient reliability. Therefore, we think that the system to compare the shape based on a quantitative evaluation is necessary. To resolve this problem, we propose the system that enables the shape of the brain neural pathway extracted by the tractography technology to be compared quantitatively. The proposed system realized to calculate similarity between two neural pathways, and to display the difference area according to the similarity. (author)

  13. Quantum neural network-based EEG filtering for a brain-computer interface.

    Science.gov (United States)

    Gandhi, Vaibhav; Prasad, Girijesh; Coyle, Damien; Behera, Laxmidhar; McGinnity, Thomas Martin

    2014-02-01

    A novel neural information processing architecture inspired by quantum mechanics and incorporating the well-known Schrodinger wave equation is proposed in this paper. The proposed architecture referred to as recurrent quantum neural network (RQNN) can characterize a nonstationary stochastic signal as time-varying wave packets. A robust unsupervised learning algorithm enables the RQNN to effectively capture the statistical behavior of the input signal and facilitates the estimation of signal embedded in noise with unknown characteristics. The results from a number of benchmark tests show that simple signals such as dc, staircase dc, and sinusoidal signals embedded within high noise can be accurately filtered and particle swarm optimization can be employed to select model parameters. The RQNN filtering procedure is applied in a two-class motor imagery-based brain-computer interface where the objective was to filter electroencephalogram (EEG) signals before feature extraction and classification to increase signal separability. A two-step inner-outer fivefold cross-validation approach is utilized to select the algorithm parameters subject-specifically for nine subjects. It is shown that the subject-specific RQNN EEG filtering significantly improves brain-computer interface performance compared to using only the raw EEG or Savitzky-Golay filtered EEG across multiple sessions.

  14. Spatio-temporal neural stem cell behavior that leads to both perfect and imperfect structural brain regeneration in adult newts.

    Science.gov (United States)

    Urata, Yuko; Yamashita, Wataru; Inoue, Takeshi; Agata, Kiyokazu

    2018-06-14

    Adult newts can regenerate large parts of their brain from adult neural stem cells (NSCs), but how adult NSCs reorganize brain structures during regeneration remains unclear. In development, elaborate brain structures are produced under broadly coordinated regulations of embryonic NSCs in the neural tube, whereas brain regeneration entails exquisite control of the reestablishment of certain brain parts, suggesting a yet-unknown mechanism directs NSCs upon partial brain excision. Here we report that upon one-quarter excision of the adult newt ( Pleurodeles waltl ) mesencephalon, active participation of local NSCs around specific brain subregions' boundaries leads to some imperfect and some perfect brain regeneration along an individual's rostrocaudal axis. Regeneration phenotypes depend on how the wound closing occurs using local NSCs, and perfect regeneration replicates development-like processes but takes more than one year. Our findings indicate that newt brain regeneration is supported by modularity of boundary-domain NSCs with self-organizing ability in neighboring fields. © 2018. Published by The Company of Biologists Ltd.

  15. Brain tumor segmentation with Deep Neural Networks.

    Science.gov (United States)

    Havaei, Mohammad; Davy, Axel; Warde-Farley, David; Biard, Antoine; Courville, Aaron; Bengio, Yoshua; Pal, Chris; Jodoin, Pierre-Marc; Larochelle, Hugo

    2017-01-01

    In this paper, we present a fully automatic brain tumor segmentation method based on Deep Neural Networks (DNNs). The proposed networks are tailored to glioblastomas (both low and high grade) pictured in MR images. By their very nature, these tumors can appear anywhere in the brain and have almost any kind of shape, size, and contrast. These reasons motivate our exploration of a machine learning solution that exploits a flexible, high capacity DNN while being extremely efficient. Here, we give a description of different model choices that we've found to be necessary for obtaining competitive performance. We explore in particular different architectures based on Convolutional Neural Networks (CNN), i.e. DNNs specifically adapted to image data. We present a novel CNN architecture which differs from those traditionally used in computer vision. Our CNN exploits both local features as well as more global contextual features simultaneously. Also, different from most traditional uses of CNNs, our networks use a final layer that is a convolutional implementation of a fully connected layer which allows a 40 fold speed up. We also describe a 2-phase training procedure that allows us to tackle difficulties related to the imbalance of tumor labels. Finally, we explore a cascade architecture in which the output of a basic CNN is treated as an additional source of information for a subsequent CNN. Results reported on the 2013 BRATS test data-set reveal that our architecture improves over the currently published state-of-the-art while being over 30 times faster. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Delineating Neural Structures of Developmental Human Brains with Diffusion Tensor Imaging

    Directory of Open Access Journals (Sweden)

    Hao Huang

    2010-01-01

    Full Text Available The human brain anatomy is characterized by dramatic structural changes during fetal development. It is extraordinarily complex and yet its origin is a simple tubular structure. Revealing detailed anatomy at different stages of brain development not only aids in understanding this highly ordered process, but also provides clues to detect abnormalities caused by genetic or environmental factors. However, anatomical studies of human brain development during the fetal period are surprisingly scarce and histology-based atlases have become available only recently. Diffusion tensor imaging (DTI measures water diffusion to delineate the underlying neural structures. The high contrasts derived from DTI can be used to establish the brain atlas. With DTI tractography, coherent neural structures, such as white matter tracts, can be three-dimensionally reconstructed. The primary eigenvector of the diffusion tensor can be further explored to characterize microstructures in the cerebral wall of the developmental brains. In this mini-review, the application of DTI in order to reveal the structures of developmental fetal brains has been reviewed in the above-mentioned aspects. The fetal brain DTI provides a unique insight for delineating the neural structures in both macroscopic and microscopic levels. The resultant DTI database will provide structural guidance for the developmental study of human fetal brains in basic neuroscience, and reference standards for diagnostic radiology of premature newborns.

  17. Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering.

    Science.gov (United States)

    Cheng, Tzu-Yun; Chen, Ming-Hong; Chang, Wen-Han; Huang, Ming-Yuan; Wang, Tzu-Wei

    2013-03-01

    Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer β-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA(16)-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Programmable neural processing on a smartdust for brain-computer interfaces.

    Science.gov (United States)

    Yuwen Sun; Shimeng Huang; Oresko, Joseph J; Cheng, Allen C

    2010-10-01

    Brain-computer interfaces (BCIs) offer tremendous promise for improving the quality of life for disabled individuals. BCIs use spike sorting to identify the source of each neural firing. To date, spike sorting has been performed by either using off-chip analysis, which requires a wired connection penetrating the skull to a bulky external power/processing unit, or via custom application-specific integrated circuits that lack the programmability to perform different algorithms and upgrades. In this research, we propose and test the feasibility of performing on-chip, real-time spike sorting on a programmable smartdust, including feature extraction, classification, compression, and wireless transmission. A detailed power/performance tradeoff analysis using DVFS is presented. Our experimental results show that the execution time and power density meet the requirements to perform real-time spike sorting and wireless transmission on a single neural channel.

  19. Immunocapture-based fluorometric assay for the measurement of neprilysin-specific enzyme activity in brain tissue homogenates and cerebrospinal fluid.

    NARCIS (Netherlands)

    Miners, J.S.; Verbeek, M.M.; Olde Rikkert, M.G.M.; Kehoe, P.G.; Love, S.

    2008-01-01

    Neprilysin, a zinc-metalloendopeptidase, has important roles in the physiology and pathology of many diseases such as hypertension, cancer and Alzheimer's disease. We have developed an immunocapture assay to measure the specific enzyme activity of neprilysin in brain tissue homogenates and

  20. Nanosized zinc oxide particles induce neural stem cell apoptosis

    International Nuclear Information System (INIS)

    Deng Xiaoyong; Luan Qixia; Wu Minghong; Zhang Haijiao; Jiao Zheng; Chen Wenting; Wang Yanli

    2009-01-01

    Given the intensive application of nanoscale zinc oxide (ZnO) materials in our life, growing concerns have arisen about its unintentional health and environmental impacts. In this study, the neurotoxicity of different sized ZnO nanoparticles in mouse neural stem cells (NSCs) was investigated. A cell viability assay indicated that ZnO nanoparticles manifested dose-dependent, but no size-dependent toxic effects on NSCs. Apoptotic cells were observed and analyzed by confocal microscopy, transmission electron microscopy examination, and flow cytometry. All the results support the viewpoint that the ZnO nanoparticle toxicity comes from the dissolved Zn 2+ in the culture medium or inside cells. Our results highlight the need for caution during the use and disposal of ZnO manufactured nanomaterials to prevent the unintended environmental and health impacts.

  1. Transcriptional profiling of adult neural stem-like cells from the human brain.

    Directory of Open Access Journals (Sweden)

    Cecilie Jonsgar Sandberg

    Full Text Available There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60. Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate. We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6, foetal human neural stem cells (n = 1 and human brain tissues (n = 12. The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular

  2. Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth.

    Science.gov (United States)

    Lim, Nicholas R; Shohayeb, Belal; Zaytseva, Olga; Mitchell, Naomi; Millard, S Sean; Ng, Dominic C H; Quinn, Leonie M

    2017-07-11

    The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume. Moreover, loss of function in glia not only decreased the glial population but also non-autonomously caused neuroblast loss. We further demonstrated that WDR62 controls brain growth through lineage-specific interactions with master mitotic signaling kinase, AURKA. Depletion of AURKA in neuroblasts drives brain overgrowth, which was suppressed by WDR62 co-depletion. In contrast, glial-specific depletion of AURKA significantly decreased brain volume, which was further decreased by WDR62 co-depletion. Thus, dissecting relative contributions of MCPH factors to individual neural lineages will be critical for understanding complex diseases such as microcephaly. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  3. Models of neural dynamics in brain information processing - the developments of 'the decade'

    International Nuclear Information System (INIS)

    Borisyuk, G N; Borisyuk, R M; Kazanovich, Yakov B; Ivanitskii, Genrikh R

    2002-01-01

    Neural network models are discussed that have been developed during the last decade with the purpose of reproducing spatio-temporal patterns of neural activity in different brain structures. The main goal of the modeling was to test hypotheses of synchronization, temporal and phase relations in brain information processing. The models being considered are those of temporal structure of spike sequences, of neural activity dynamics, and oscillatory models of attention and feature integration. (reviews of topical problems)

  4. Elimination of zinc-65 from the brain under kainate-induced seizures.

    Science.gov (United States)

    Takeda, Atsushi; Hirate, Maki; Oku, Naoto

    2004-04-01

    On the basis of the previous evidence that 65Zn concentrations in the brain of EL (epilepsy) mice was affected by induction of seizures, 65Zn movement in the brain was quantitatively evaluated in ddY mice treated with kainate. Six days after intravenous injection of 65ZnCl2, mice were intraperitoneally injected with kainate (10 mg/kg x 6 times in 2 weeks). Myoclonic jerks were observed during treatment with kainate. Twenty days after 65Zn injection, 65Zn distribution in the brain was compared between the kainite-treated and control mice. 65Zn distribution in the brain of the kainate-treated mice was overall lower than in the control mice. 65Zn concentration was significantly decreased in the frontal cortex, hippocampal CA1, thalamus and hypothalamus by treatment with kainate. These results demonstrate that kainate-induced seizures are linked to decreased zinc concentrations in the brain.

  5. Using brain stimulation to disentangle neural correlates of conscious vision

    NARCIS (Netherlands)

    de Graaf, T.A.; Sack, A.T.

    2014-01-01

    Research into the neural correlates of consciousness (NCCs) has blossomed, due to the advent of new and increasingly sophisticated brain research tools. Neuroimaging has uncovered a variety of brain processes that relate to conscious perception, obtained in a range of experimental paradigms. But

  6. Brain responses in 4-month-old infants are already language specific.

    Science.gov (United States)

    Friederici, Angela D; Friedrich, Manuela; Christophe, Anne

    2007-07-17

    Language is the most important faculty that distinguishes humans from other animals. Infants learn their native language fast and effortlessly during the first years of life, as a function of the linguistic input in their environment. Behavioral studies reported the discrimination of melodic contours [1] and stress patterns [2, 3] in 1-4-month-olds. Behavioral [4, 5] and brain measures [6-8] have shown language-independent discrimination of phonetic contrasts at that age. Language-specific discrimination, however, has been reported for phonetic contrasts only for 6-12-month-olds [9-12]. Here we demonstrate language-specific discrimination of stress patterns in 4-month-old German and French infants by using electrophysiological brain measures. We compare the processing of disyllabic words differing in their rhythmic structure, mimicking German words being stressed on the first syllable, e.g., pápa/daddy[13], and French ones being stressed on the second syllable, e.g., papá/daddy. Event-related brain potentials reveal that experience with German and French differentially affects the brain responses of 4-month-old infants, with each language group displaying a processing advantage for the rhythmic structure typical in its native language. These data indicate language-specific neural representations of word forms in the infant brain as early as 4 months of age.

  7. NeuroMEMS: Neural Probe Microtechnologies

    Directory of Open Access Journals (Sweden)

    Sam Musallam

    2008-10-01

    Full Text Available Neural probe technologies have already had a significant positive effect on our understanding of the brain by revealing the functioning of networks of biological neurons. Probes are implanted in different areas of the brain to record and/or stimulate specific sites in the brain. Neural probes are currently used in many clinical settings for diagnosis of brain diseases such as seizers, epilepsy, migraine, Alzheimer’s, and dementia. We find these devices assisting paralyzed patients by allowing them to operate computers or robots using their neural activity. In recent years, probe technologies were assisted by rapid advancements in microfabrication and microelectronic technologies and thus are enabling highly functional and robust neural probes which are opening new and exciting avenues in neural sciences and brain machine interfaces. With a wide variety of probes that have been designed, fabricated, and tested to date, this review aims to provide an overview of the advances and recent progress in the microfabrication techniques of neural probes. In addition, we aim to highlight the challenges faced in developing and implementing ultralong multi-site recording probes that are needed to monitor neural activity from deeper regions in the brain. Finally, we review techniques that can improve the biocompatibility of the neural probes to minimize the immune response and encourage neural growth around the electrodes for long term implantation studies.

  8. Flexible deep brain neural probes based on a parylene tube structure

    Science.gov (United States)

    Zhao, Zhiguo; Kim, Eric; Luo, Hao; Zhang, Jinsheng; Xu, Yong

    2018-01-01

    Most microfabricated neural probes have limited shank length, which prevents them from reaching many deep brain structures. This paper reports deep brain neural probes with ultra-long penetrating shanks based on a simple but novel parylene tube structure. The mechanical strength of the parylene tube shank is temporarily enhanced during implantation by inserting a metal wire. The metal wire can be removed after implantation, making the implanted probe very flexible and thus minimizing the stress caused by micromotions of brain tissues. Optogenetic stimulation and chemical delivery capabilities can be potentially integrated by taking advantage of the tube structure. Single-shank prototypes with a shank length of 18.2 mm have been developed. The microfabrication process comprises of deep reactive ion etching (DRIE) of silicon, parylene conformal coating/refilling, and XeF2 isotropic silicon etching. In addition to bench-top insertion characterization, the functionality of developed probes has been preliminarily demonstrated by implanting into the amygdala of a rat and recording neural signals.

  9. Ketamine-induced behavioural and brain oxidative changes in mice: an assessment of possible beneficial effects of zinc as mono- or adjunct therapy.

    Science.gov (United States)

    Onaolapo, Olakunle James; Ademakinwa, Olayemi Quyyom; Olalekan, Temitayo Opeyemi; Onaolapo, Adejoke Yetunde

    2017-09-01

    We studied the influence of zinc, haloperidol or olanzapine on neurobehaviour (open-field, radial arm maze and elevated plus maze) and brain antioxidant status in vehicle- or ketamine-treated mice, with the aim of ascertaining the potentials of zinc in counteracting ketamine's effects. Experiment 1 assessed the effects of zinc in healthy animals and the relative degrees of modulation of ketamine's effects by zinc, haloperidol or olanzapine, respectively. Experiment 2 assessed the modulation of ketamine's effects following co-administration of zinc with haloperidol or olanzapine. Male mice weighing 18-20 g each were used. Animals were pretreated with ketamine (except vehicle, zinc, haloperidol and olanzapine controls) for 10 days before commencement of 14-day treatment (day 11-24) with vehicle, zinc, haloperidol or olanzapine (alone or in combination). Ketamine injection also continued alongside zinc and/or standard drugs in the ketamine-treated groups. Zinc, haloperidol and olanzapine were administered by gavage. Treatments were given daily and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for estimation of glutathione, nitric oxide and malondialdehyde (MDA) levels. Ketamine increased open-field behaviours, nitric oxide and MDA levels, while it decreased working memory, social interaction and glutathione. Administration of zinc alone or in combination with haloperidol or olanzapine was associated with variable degrees of reversal of these effects. Zinc may have the potential of a possible therapeutic agent and/or adjunct in the reversal of schizophrenia-like changes in behaviour and brain oxidative status.

  10. Morphological covariance in anatomical MRI scans can identify discrete neural pathways in the brain and their disturbances in persons with neuropsychiatric disorders.

    Science.gov (United States)

    Bansal, Ravi; Hao, Xuejun; Peterson, Bradley S

    2015-05-01

    We hypothesize that coordinated functional activity within discrete neural circuits induces morphological organization and plasticity within those circuits. Identifying regions of morphological covariation that are independent of morphological covariation in other regions therefore may therefore allow us to identify discrete neural systems within the brain. Comparing the magnitude of these variations in individuals who have psychiatric disorders with the magnitude of variations in healthy controls may allow us to identify aberrant neural pathways in psychiatric illnesses. We measured surface morphological features by applying nonlinear, high-dimensional warping algorithms to manually defined brain regions. We transferred those measures onto the surface of a unit sphere via conformal mapping and then used spherical wavelets and their scaling coefficients to simplify the data structure representing these surface morphological features of each brain region. We used principal component analysis (PCA) to calculate covariation in these morphological measures, as represented by their scaling coefficients, across several brain regions. We then assessed whether brain subregions that covaried in morphology, as identified by large eigenvalues in the PCA, identified specific neural pathways of the brain. To do so, we spatially registered the subnuclei for each eigenvector into the coordinate space of a Diffusion Tensor Imaging dataset; we used these subnuclei as seed regions to track and compare fiber pathways with known fiber pathways identified in neuroanatomical atlases. We applied these procedures to anatomical MRI data in a cohort of 82 healthy participants (42 children, 18 males, age 10.5 ± 2.43 years; 40 adults, 22 males, age 32.42 ± 10.7 years) and 107 participants with Tourette's Syndrome (TS) (71 children, 59 males, age 11.19 ± 2.2 years; 36 adults, 21 males, age 37.34 ± 10.9 years). We evaluated the construct validity of the identified covariation in morphology

  11. Information-geometric measures estimate neural interactions during oscillatory brain states

    Directory of Open Access Journals (Sweden)

    Yimin eNie

    2014-02-01

    Full Text Available The characterization of functional network structures among multiple neurons is essential to understanding neural information processing. Information geometry (IG, a theory developed for investigating a space of probability distributions has recently been applied to spike-train analysis and has provided robust estimations of neural interactions. Although neural firing in the equilibrium state is often assumed in these studies, in reality, neural activity is non-stationary. The brain exhibits various oscillations depending on cognitive demands or when an animal is asleep. Therefore, the investigation of the IG measures during oscillatory network states is important for testing how the IG method can be applied to real neural data. Using model networks of binary neurons or more realistic spiking neurons, we studied how the single- and pairwise-IG measures were influenced by oscillatory neural activity. Two general oscillatory mechanisms, externally driven oscillations and internally induced oscillations, were considered. In both mechanisms, we found that the single-IG measure was linearly related to the magnitude of the external input, and that the pairwise-IG measure was linearly related to the sum of connection strengths between two neurons. We also observed that the pairwise-IG measure was not dependent on the oscillation frequency. These results are consistent with the previous findings that were obtained under the equilibrium conditions. Therefore, we demonstrate that the IG method provides useful insights into neural interactions under the oscillatory condition that can often be observed in the real brain.

  12. Isointense infant brain MRI segmentation with a dilated convolutional neural network

    NARCIS (Netherlands)

    Moeskops, P.; Pluim, J.P.W.

    2017-01-01

    Quantitative analysis of brain MRI at the age of 6 months is difficult because of the limited contrast between white matter and gray matter. In this study, we use a dilated triplanar convolutional neural network in combination with a non-dilated 3D convolutional neural network for the segmentation

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

    Science.gov (United States)

    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 (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. © 2015 Wiley Periodicals, Inc.

  14. Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.

    Science.gov (United States)

    Zhang, Hongsheng; Kang, Eunchai; Wang, Yaqing; Yang, Chaojuan; Yu, Hui; Wang, Qin; Chen, Zheyu; Zhang, Chen; Christian, Kimberly M; Song, Hongjun; Ming, Guo-Li; Xu, Zhiheng

    2016-06-01

    Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

  15. The flexible brain. On mind and brain, neural darwinism and psychiatry.

    Science.gov (United States)

    den Boer, J A

    1997-09-01

    A theoretical introduction is given in which several theoretical viewpoints concerning the mind-brain problem are discussed. During the last decade philosophers like Searle, Dennett and the Churchlands have taken a more or less pure materialistic position in explaining mental phenomena. Investigators in biological psychiatry have hardly ever taken a clear position in this discussion, whereas we believe it is important that the conclusions drawn from biological research are embedded in a theoretical framework related to the mind-brain problem. In this article the thesis is defended that the theory of neural darwinism represents a major step forward and may bridge previous distinctions between biological, clinical and social psychiatry.

  16. Neural codes of seeing architectural styles

    OpenAIRE

    Choo, Heeyoung; Nasar, Jack L.; Nikrahei, Bardia; Walther, Dirk B.

    2017-01-01

    Images of iconic buildings, such as the CN Tower, instantly transport us to specific places, such as Toronto. Despite the substantial impact of architectural design on people′s visual experience of built environments, we know little about its neural representation in the human brain. In the present study, we have found patterns of neural activity associated with specific architectural styles in several high-level visual brain regions, but not in primary visual cortex (V1). This finding sugges...

  17. Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

    Institute of Scientific and Technical Information of China (English)

    Weiliang Zhao; Dezhi Kang; Yuanxiang Lin

    2008-01-01

    BACKGROUND: Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE: To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY: A computer-based online search was conducted in PUBMED for English language publications containing the key words "brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor" from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria: ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS: After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these

  18. Automatic segmentation of MR brain images with a convolutional neural network

    NARCIS (Netherlands)

    Moeskops, P.; Viergever, M.A.; Mendrik, A.M.; de Vries, L.S.; Benders, M.J.N.L.; Išgum, I.

    2016-01-01

    Automatic segmentation in MR brain images is important for quantitative analysis in large-scale studies with images acquired at all ages. This paper presents a method for the automatic segmentation of MR brain images into a number of tissue classes using a convolutional neural network. To ensure

  19. Using Neural Pattern Classifiers to Quantify the Modularity of Conflict–Control Mechanisms in the Human Brain

    Science.gov (United States)

    Jiang, Jiefeng; Egner, Tobias

    2014-01-01

    Resolving conflicting sensory and motor representations is a core function of cognitive control, but it remains uncertain to what degree control over different sources of conflict is implemented by shared (domain general) or distinct (domain specific) neural resources. Behavioral data suggest conflict–control to be domain specific, but results from neuroimaging studies have been ambivalent. Here, we employed multivoxel pattern analyses that can decode a brain region's informational content, allowing us to distinguish incidental activation overlap from actual shared information processing. We trained independent sets of “searchlight” classifiers on functional magnetic resonance imaging data to decode control processes associated with stimulus-conflict (Stroop task) and ideomotor-conflict (Simon task). Quantifying the proportion of domain-specific searchlights (capable of decoding only one type of conflict) and domain-general searchlights (capable of decoding both conflict types) in each subject, we found both domain-specific and domain-general searchlights, though the former were more common. When mapping anatomical loci of these searchlights across subjects, neural substrates of stimulus- and ideomotor-specific conflict–control were found to be anatomically consistent across subjects, whereas the substrates of domain-general conflict–control were not. Overall, these findings suggest a hybrid neural architecture of conflict–control that entails both modular (domain specific) and global (domain general) components. PMID:23402762

  20. Neural imaginaries and clinical epistemology: Rhetorically mapping the adolescent brain in the clinical encounter.

    Science.gov (United States)

    Buchbinder, Mara

    2015-10-01

    The social work of brain images has taken center stage in recent theorizing of the intersections between neuroscience and society. However, neuroimaging is only one of the discursive modes through which public representations of neurobiology travel. This article adopts an expanded view toward the social implications of neuroscientific thinking to examine how neural imaginaries are constructed in the absence of visual evidence. Drawing on ethnographic fieldwork conducted over 18 months (2008-2009) in a United States multidisciplinary pediatric pain clinic, I examine the pragmatic clinical work undertaken to represent ambiguous symptoms in neurobiological form. Focusing on one physician, I illustrate how, by rhetorically mapping the brain as a therapeutic tool, she engaged in a distinctive form of representation that I call neural imagining. In shifting my focus away from the purely material dimensions of brain images, I juxtapose the cultural work of brain scanning technologies with clinical neural imaginaries in which the teenage brain becomes a space of possibility, not to map things as they are, but rather, things as we hope they might be. These neural imaginaries rely upon a distinctive clinical epistemology that privileges the creative work of the imagination over visualization technologies in revealing the truths of the body. By creating a therapeutic space for adolescents to exercise their imaginative faculties and a discursive template for doing so, neural imagining relocates adolescents' agency with respect to epistemologies of bodily knowledge and the role of visualization practices therein. In doing so, it provides a more hopeful alternative to the dominant popular and scientific representations of the teenage brain that view it primarily through the lens of pathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Topographic factor analysis: a Bayesian model for inferring brain networks from neural data.

    Directory of Open Access Journals (Sweden)

    Jeremy R Manning

    Full Text Available The neural patterns recorded during a neuroscientific experiment reflect complex interactions between many brain regions, each comprising millions of neurons. However, the measurements themselves are typically abstracted from that underlying structure. For example, functional magnetic resonance imaging (fMRI datasets comprise a time series of three-dimensional images, where each voxel in an image (roughly reflects the activity of the brain structure(s-located at the corresponding point in space-at the time the image was collected. FMRI data often exhibit strong spatial correlations, whereby nearby voxels behave similarly over time as the underlying brain structure modulates its activity. Here we develop topographic factor analysis (TFA, a technique that exploits spatial correlations in fMRI data to recover the underlying structure that the images reflect. Specifically, TFA casts each brain image as a weighted sum of spatial functions. The parameters of those spatial functions, which may be learned by applying TFA to an fMRI dataset, reveal the locations and sizes of the brain structures activated while the data were collected, as well as the interactions between those structures.

  2. Neural Activity Patterns in the Human Brain Reflect Tactile Stickiness Perception

    Science.gov (United States)

    Kim, Junsuk; Yeon, Jiwon; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

    2017-01-01

    Our previous human fMRI study found brain activations correlated with tactile stickiness perception using the uni-variate general linear model (GLM) (Yeon et al., 2017). Here, we conducted an in-depth investigation on neural correlates of sticky sensations by employing a multivoxel pattern analysis (MVPA) on the same dataset. In particular, we statistically compared multi-variate neural activities in response to the three groups of sticky stimuli: A supra-threshold group including a set of sticky stimuli that evoked vivid sticky perception; an infra-threshold group including another set of sticky stimuli that barely evoked sticky perception; and a sham group including acrylic stimuli with no physically sticky property. Searchlight MVPAs were performed to search for local activity patterns carrying neural information of stickiness perception. Similar to the uni-variate GLM results, significant multi-variate neural activity patterns were identified in postcentral gyrus, subcortical (basal ganglia and thalamus), and insula areas (insula and adjacent areas). Moreover, MVPAs revealed that activity patterns in posterior parietal cortex discriminated the perceptual intensities of stickiness, which was not present in the uni-variate analysis. Next, we applied a principal component analysis (PCA) to the voxel response patterns within identified clusters so as to find low-dimensional neural representations of stickiness intensities. Follow-up clustering analyses clearly showed separate neural grouping configurations between the Supra- and Infra-threshold groups. Interestingly, this neural categorization was in line with the perceptual grouping pattern obtained from the psychophysical data. Our findings thus suggest that different stickiness intensities would elicit distinct neural activity patterns in the human brain and may provide a neural basis for the perception and categorization of tactile stickiness. PMID:28936171

  3. Models of neural dynamics in brain information processing - the developments of 'the decade'

    Energy Technology Data Exchange (ETDEWEB)

    Borisyuk, G N; Borisyuk, R M; Kazanovich, Yakov B [Institute of Mathematical Problems of Biology, Russian Academy of Sciences, Pushchino, Moscow region (Russian Federation); Ivanitskii, Genrikh R [Institute for Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow region (Russian Federation)

    2002-10-31

    Neural network models are discussed that have been developed during the last decade with the purpose of reproducing spatio-temporal patterns of neural activity in different brain structures. The main goal of the modeling was to test hypotheses of synchronization, temporal and phase relations in brain information processing. The models being considered are those of temporal structure of spike sequences, of neural activity dynamics, and oscillatory models of attention and feature integration. (reviews of topical problems)

  4. The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line.

    Science.gov (United States)

    Fujiwara, Yuki; Miyazaki, Wataru; Koibuchi, Noriyuki; Katoh, Takahiko

    2018-01-01

    Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF), an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP), and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

  5. The Effects of Low-Dose Bisphenol A and Bisphenol F on Neural Differentiation of a Fetal Brain-Derived Neural Progenitor Cell Line

    Directory of Open Access Journals (Sweden)

    Yuki Fujiwara

    2018-02-01

    Full Text Available Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA, which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF, an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as β III-tubulin and glial fibrillary acidic protein (GFAP, and Olig2. The β III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of β III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

  6. Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders.

    Science.gov (United States)

    O'Donnell, Cian; Gonçalves, J Tiago; Portera-Cailliau, Carlos; Sejnowski, Terrence J

    2017-10-11

    A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here, we combined computational simulations with analysis of in vivo two-photon Ca 2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; (2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; (3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher dimensional models that can better capture the multidimensional computational functions of neural circuits.

  7. In vivo target bio-imaging of Alzheimer's disease by fluorescent zinc oxide nanoclusters.

    Science.gov (United States)

    Lai, Lanmei; Zhao, Chunqiu; Su, Meina; Li, Xiaoqi; Liu, Xiaoli; Jiang, Hui; Amatore, Christian; Wang, Xuemei

    2016-07-21

    Alzheimer's disease (AD) is an irreversible neurodegenerative disease which is difficult to cure. When Alzheimer's disease occurs, the level of zinc ions in the brain changes, and the relevant amount of zinc ions continue decreasing in the cerebrospinal fluid and plasma of Alzheimer's patients with disease exacerbation. In view of these considerations, we have explored a new strategy for the in vivo rapid fluorescence imaging of Alzheimer's disease through target bio-labeling of zinc oxide nanoclusters which were biosynthesized in vivo in the Alzheimer's brain via intravenous injection of zinc gluconate solution. By using three-month-old and six-month-old Alzheimer's model mice as models, our observations demonstrate that biocompatible zinc ions could pass through the blood-brain barrier of the Alzheimer's disease mice and generate fluorescent zinc oxide nanoclusters (ZnO NCs) through biosynthesis, and then the bio-synthesized ZnO NCs could readily accumulate in situ on the hippocampus specific region for the in vivo fluorescent labeling of the affected sites. This study provides a new way for the rapid diagnosis of Alzheimer's disease and may have promising prospects in the effective diagnosis of Alzheimer's disease.

  8. Patterns recognition of electric brain activity using artificial neural networks

    Science.gov (United States)

    Musatov, V. Yu.; Pchelintseva, S. V.; Runnova, A. E.; Hramov, A. E.

    2017-04-01

    An approach for the recognition of various cognitive processes in the brain activity in the perception of ambiguous images. On the basis of developed theoretical background and the experimental data, we propose a new classification of oscillating patterns in the human EEG by using an artificial neural network approach. After learning of the artificial neural network reliably identified cube recognition processes, for example, left-handed or right-oriented Necker cube with different intensity of their edges, construct an artificial neural network based on Perceptron architecture and demonstrate its effectiveness in the pattern recognition of the EEG in the experimental.

  9. Effects of nanoparticle zinc oxide on emotional behavior and trace elements homeostasis in rat brain.

    Science.gov (United States)

    Amara, Salem; Slama, Imen Ben; Omri, Karim; El Ghoul, Jaber; El Mir, Lassaad; Rhouma, Khemais Ben; Abdelmelek, Hafedh; Sakly, Mohsen

    2015-12-01

    Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20-30 nm) at a dose of 25 mg/kg body weight. Sub -: acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain. © The Author(s) 2012.

  10. Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures

    Science.gov (United States)

    Zhang, Feng; Gradinaru, Viviana; Adamantidis, Antoine R; Durand, Remy; Airan, Raag D; de Lecea, Luis; Deisseroth, Karl

    2015-01-01

    Elucidation of the neural substrates underlying complex animal behaviors depends on precise activity control tools, as well as compatible readout methods. Recent developments in optogenetics have addressed this need, opening up new possibilities for systems neuroscience. Interrogation of even deep neural circuits can be conducted by directly probing the necessity and sufficiency of defined circuit elements with millisecond-scale, cell type-specific optical perturbations, coupled with suitable readouts such as electrophysiology, optical circuit dynamics measures and freely moving behavior in mammals. Here we collect in detail our strategies for delivering microbial opsin genes to deep mammalian brain structures in vivo, along with protocols for integrating the resulting optical control with compatible readouts (electrophysiological, optical and behavioral). The procedures described here, from initial virus preparation to systems-level functional readout, can be completed within 4–5 weeks. Together, these methods may help in providing circuit-level insight into the dynamics underlying complex mammalian behaviors in health and disease. PMID:20203662

  11. Neural signatures of third-party punishment: evidence from penetrating traumatic brain injury.

    Science.gov (United States)

    Glass, Leila; Moody, Lara; Grafman, Jordan; Krueger, Frank

    2016-02-01

    The ability to survive within a cooperative society depends on impartial third-party punishment (TPP) of social norm violations. Two cognitive mechanisms have been postulated as necessary for the successful completion of TPP: evaluation of legal responsibility and selection of a suitable punishment given the magnitude of the crime. Converging neuroimaging research suggests two supporting domain-general networks; a mentalizing network for evaluation of legal responsibility and a central-executive network for determination of punishment. A whole-brain voxel-based lesion-symptom mapping approach was used in conjunction with a rank-order TPP task to identify brain regions necessary for TPP in a large sample of patients with penetrating traumatic brain injury. Patients who demonstrated atypical TPP had specific lesions in core regions of the mentalizing (dorsomedial prefrontal cortex [PFC], ventromedial PFC) and central-executive (bilateral dorsolateral PFC, right intraparietal sulcus) networks. Altruism and executive functioning (concept formation skills) were significant predictors of TPP: altruism was uniquely associated with TPP in patients with lesions in right dorsolateral PFC and executive functioning was uniquely associated with TPP in individuals with lesions in left PFC. Our findings contribute to the extant literature to support underlying neural networks associated with TPP, with specific brain-behavior causal relationships confirming recent functional neuroimaging research. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  12. Neural codes of seeing architectural styles.

    Science.gov (United States)

    Choo, Heeyoung; Nasar, Jack L; Nikrahei, Bardia; Walther, Dirk B

    2017-01-10

    Images of iconic buildings, such as the CN Tower, instantly transport us to specific places, such as Toronto. Despite the substantial impact of architectural design on people's visual experience of built environments, we know little about its neural representation in the human brain. In the present study, we have found patterns of neural activity associated with specific architectural styles in several high-level visual brain regions, but not in primary visual cortex (V1). This finding suggests that the neural correlates of the visual perception of architectural styles stem from style-specific complex visual structure beyond the simple features computed in V1. Surprisingly, the network of brain regions representing architectural styles included the fusiform face area (FFA) in addition to several scene-selective regions. Hierarchical clustering of error patterns further revealed that the FFA participated to a much larger extent in the neural encoding of architectural styles than entry-level scene categories. We conclude that the FFA is involved in fine-grained neural encoding of scenes at a subordinate-level, in our case, architectural styles of buildings. This study for the first time shows how the human visual system encodes visual aspects of architecture, one of the predominant and longest-lasting artefacts of human culture.

  13. Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

    Science.gov (United States)

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-05-01

    Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

  14. Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease.

    Science.gov (United States)

    Swann, Nicole C; de Hemptinne, Coralie; Miocinovic, Svjetlana; Qasim, Salman; Ostrem, Jill L; Galifianakis, Nicholas B; Luciano, Marta San; Wang, Sarah S; Ziman, Nathan; Taylor, Robin; Starr, Philip A

    2018-02-01

    OBJECTIVE Dysfunction of distributed neural networks underlies many brain disorders. The development of neuromodulation therapies depends on a better understanding of these networks. Invasive human brain recordings have a favorable temporal and spatial resolution for the analysis of network phenomena but have generally been limited to acute intraoperative recording or short-term recording through temporarily externalized leads. Here, the authors describe their initial experience with an investigational, first-generation, totally implantable, bidirectional neural interface that allows both continuous therapeutic stimulation and recording of field potentials at multiple sites in a neural network. METHODS Under a physician-sponsored US Food and Drug Administration investigational device exemption, 5 patients with Parkinson's disease were implanted with the Activa PC+S system (Medtronic Inc.). The device was attached to a quadripolar lead placed in the subdural space over motor cortex, for electrocorticography potential recordings, and to a quadripolar lead in the subthalamic nucleus (STN), for both therapeutic stimulation and recording of local field potentials. Recordings from the brain of each patient were performed at multiple time points over a 1-year period. RESULTS There were no serious surgical complications or interruptions in deep brain stimulation therapy. Signals in both the cortex and the STN were relatively stable over time, despite a gradual increase in electrode impedance. Canonical movement-related changes in specific frequency bands in the motor cortex were identified in most but not all recordings. CONCLUSIONS The acquisition of chronic multisite field potentials in humans is feasible. The device performance characteristics described here may inform the design of the next generation of totally implantable neural interfaces. This research tool provides a platform for translating discoveries in brain network dynamics to improved neurostimulation

  15. A Role of Endogenous Progesterone in Stroke Cerebroprotection Revealed by the Neural-Specific Deletion of Its Intracellular Receptors.

    Science.gov (United States)

    Zhu, Xiaoyan; Fréchou, Magalie; Liere, Philippe; Zhang, Shaodong; Pianos, Antoine; Fernandez, Neïké; Denier, Christian; Mattern, Claudia; Schumacher, Michael; Guennoun, Rachida

    2017-11-08

    Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult. Here, we used steroid profiling by gas chromatography-tandem mass spectrometry (GC-MS/MS) for exploring adaptive and sex-specific changes in brain levels of progesterone and its metabolites after MCAO. We show that, in the male mouse brain, progesterone is mainly metabolized via 5α-reduction leading to 5α-dihydroprogesterone (5α-DHP), also a progesterone receptor (PR) agonist ligand in neural cells, then to 3α,5α-tetrahydroprogesterone (3α,5α-THP). In the female mouse brain, levels of 5α-DHP and 3α,5α-THP are lower and levels of 20α-DHP are higher than in males. After MCAO, levels of progesterone and 5α-DHP are upregulated rapidly to pregnancy-like levels in the male but not in the female brain. To assess whether endogenous progesterone and 5α-DHP contribute to the resistance of neural cells to ischemic damage, we inactivated PR selectively in the CNS. Deletion of PR in the brain reduced its resistance to MCAO, resulting in increased infarct volumes and neurological deficits in both sexes. Importantly, endogenous PR ligands continue to protect the brain of aging mice. These results uncover the unexpected importance of endogenous progesterone and its metabolites in cerebroprotection. They also reveal that the female reproductive hormone progesterone is an endogenous cerebroprotective neurosteroid in both sexes. SIGNIFICANCE STATEMENT The brain responds to injury with protective signaling and has a remarkable capacity to protect itself. We show here that, in response to ischemic stroke, levels of progesterone and its neuroactive metabolite 5α-dihydroprogesterone are upregulated rapidly in the male mouse brain but not in the

  16. Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury.

    Science.gov (United States)

    Llorens-Bobadilla, Enric; Zhao, Sheng; Baser, Avni; Saiz-Castro, Gonzalo; Zwadlo, Klara; Martin-Villalba, Ana

    2015-09-03

    Heterogeneous pools of adult neural stem cells (NSCs) contribute to brain maintenance and regeneration after injury. The balance of NSC activation and quiescence, as well as the induction of lineage-specific transcription factors, may contribute to diversity of neuronal and glial fates. To identify molecular hallmarks governing these characteristics, we performed single-cell sequencing of an unbiased pool of adult subventricular zone NSCs. This analysis identified a discrete, dormant NSC subpopulation that already expresses distinct combinations of lineage-specific transcription factors during homeostasis. Dormant NSCs enter a primed-quiescent state before activation, which is accompanied by downregulation of glycolytic metabolism, Notch, and BMP signaling and a concomitant upregulation of lineage-specific transcription factors and protein synthesis. In response to brain ischemia, interferon gamma signaling induces dormant NSC subpopulations to enter the primed-quiescent state. This study unveils general principles underlying NSC activation and lineage priming and opens potential avenues for regenerative medicine in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Using a virtual cortical module implementing a neural field model to modulate brain rhythms in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Julien Modolo

    2010-06-01

    Full Text Available We propose a new method for selective modulation of cortical rhythms based on neural field theory, in which the activity of a cortical area is extensively monitored using a two-dimensional microelectrode array. The example of Parkinson's disease illustrates the proposed method, in which a neural field model is assumed to accurately describe experimentally recorded activity. In addition, we propose a new closed-loop stimulation signal that is both space- and time- dependent. This method is especially designed to specifically modulate a targeted brain rhythm, without interfering with other rhythms. A new class of neuroprosthetic devices is also proposed, in which the multielectrode array is seen as an artificial neural network interacting with biological tissue. Such a bio-inspired approach may provide a solution to optimize interactions between the stimulation device and the cortex aiming to attenuate or augment specific cortical rhythms. The next step will be to validate this new approach experimentally in patients with Parkinson's disease.

  18. Using neural pattern classifiers to quantify the modularity of conflict-control mechanisms in the human brain.

    Science.gov (United States)

    Jiang, Jiefeng; Egner, Tobias

    2014-07-01

    Resolving conflicting sensory and motor representations is a core function of cognitive control, but it remains uncertain to what degree control over different sources of conflict is implemented by shared (domain general) or distinct (domain specific) neural resources. Behavioral data suggest conflict-control to be domain specific, but results from neuroimaging studies have been ambivalent. Here, we employed multivoxel pattern analyses that can decode a brain region's informational content, allowing us to distinguish incidental activation overlap from actual shared information processing. We trained independent sets of "searchlight" classifiers on functional magnetic resonance imaging data to decode control processes associated with stimulus-conflict (Stroop task) and ideomotor-conflict (Simon task). Quantifying the proportion of domain-specific searchlights (capable of decoding only one type of conflict) and domain-general searchlights (capable of decoding both conflict types) in each subject, we found both domain-specific and domain-general searchlights, though the former were more common. When mapping anatomical loci of these searchlights across subjects, neural substrates of stimulus- and ideomotor-specific conflict-control were found to be anatomically consistent across subjects, whereas the substrates of domain-general conflict-control were not. Overall, these findings suggest a hybrid neural architecture of conflict-control that entails both modular (domain specific) and global (domain general) components. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Natural and artificial intelligence misconceptions about brains and neural networks

    CERN Document Server

    de Callataÿ, A

    1992-01-01

    How does the mind work? How is data stored in the brain? How does the mental world connect with the physical world? The hybrid system developed in this book shows a radically new view on the brain. Briefly, in this model memory remains permanent by changing the homeostasis rebuilding the neuronal organelles. These transformations are approximately abstracted as all-or-none operations. Thus the computer-like neural systems become plausible biological models. This illustrated book shows how artificial animals with such brains learn invariant methods of behavior control from their repeated action

  20. Brain tumor segmentation in multi-spectral MRI using convolutional neural networks (CNN).

    Science.gov (United States)

    Iqbal, Sajid; Ghani, M Usman; Saba, Tanzila; Rehman, Amjad

    2018-04-01

    A tumor could be found in any area of the brain and could be of any size, shape, and contrast. There may exist multiple tumors of different types in a human brain at the same time. Accurate tumor area segmentation is considered primary step for treatment of brain tumors. Deep Learning is a set of promising techniques that could provide better results as compared to nondeep learning techniques for segmenting timorous part inside a brain. This article presents a deep convolutional neural network (CNN) to segment brain tumors in MRIs. The proposed network uses BRATS segmentation challenge dataset which is composed of images obtained through four different modalities. Accordingly, we present an extended version of existing network to solve segmentation problem. The network architecture consists of multiple neural network layers connected in sequential order with the feeding of Convolutional feature maps at the peer level. Experimental results on BRATS 2015 benchmark data thus show the usability of the proposed approach and its superiority over the other approaches in this area of research. © 2018 Wiley Periodicals, Inc.

  1. Implications of the dependence of neuronal activity on neural network states for the design of brain-machine interfaces

    Directory of Open Access Journals (Sweden)

    Stefano ePanzeri

    2016-04-01

    Full Text Available Brain-machine interfaces (BMIs can improve the quality of life of patients with sensory and motor disabilities by both decoding motor intentions expressed by neural activity, and by encoding artificially sensed information into patterns of neural activity elicited by causal interventions on the neural tissue. Yet, current BMIs can exchange relatively small amounts of information with the brain. This problem has proved difficult to overcome by simply increasing the number of recording or stimulating electrodes, because trial-to-trial variability of neural activity partly arises from intrinsic factors (collectively known as the network state that include ongoing spontaneous activity and neuromodulation, and so is shared among neurons. Here we review recent progress in characterizing the state dependence of neural responses, and in particular of how neural responses depend on endogenous slow fluctuations of network excitability. We then elaborate on how this knowledge may be used to increase the amount of information that BMIs exchange with brains. Knowledge of network state can be used to fine-tune the stimulation pattern that should reliably elicit a target neural response used to encode information in the brain, and to discount part of the trial-by-trial variability of neural responses, so that they can be decoded more accurately.

  2. Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes

    DEFF Research Database (Denmark)

    Penkowa, Milena; Giralt, M.; Thomsen, Pernille Sjølin

    2001-01-01

    , and this response was significantly blunted by zinc deficiency. The MT-III isoform was moderately increased by both TBI and zinc deficiency. TBI strongly increased oxidative stress levels, as demonstrated by malondialdehyde (MDA), protein tyrosine nitration (NITT), and nuclear factor kappaB (NF-kappaB) levels irs......, all of which were potentiated by zinc deficiency. Further analysis revealed unbalanced expression of prooxidant and antioxidant proteins besides MT, since the levels of inducible nitric oxide synthase (iNOS) and Cu,Zn-SOD were increased and decreased, respectively, by zinc deficiency. All......The role of zinc- and copper-deficient diets on the inflammatory response to traumatic brain injury (TBI) has been evaluated in adult rats. As expected, zinc deficiency decreased food intake and body weight gain, and the latter effect was higher than that observed in pair-fed rats. In noninjured...

  3. Laminar-specific distribution of zinc: evidence for presence of layer IV in forelimb motor cortex in the rat.

    Science.gov (United States)

    Alaverdashvili, Mariam; Hackett, Mark J; Pickering, Ingrid J; Paterson, Phyllis G

    2014-12-01

    The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a "Zn valley" in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding

  4. Volumetric multimodality neural network for brain tumor segmentation

    Science.gov (United States)

    Silvana Castillo, Laura; Alexandra Daza, Laura; Carlos Rivera, Luis; Arbeláez, Pablo

    2017-11-01

    Brain lesion segmentation is one of the hardest tasks to be solved in computer vision with an emphasis on the medical field. We present a convolutional neural network that produces a semantic segmentation of brain tumors, capable of processing volumetric data along with information from multiple MRI modalities at the same time. This results in the ability to learn from small training datasets and highly imbalanced data. Our method is based on DeepMedic, the state of the art in brain lesion segmentation. We develop a new architecture with more convolutional layers, organized in three parallel pathways with different input resolution, and additional fully connected layers. We tested our method over the 2015 BraTS Challenge dataset, reaching an average dice coefficient of 84%, while the standard DeepMedic implementation reached 74%.

  5. Engineering the Brain: Ethical Issues and the Introduction of Neural Devices.

    Science.gov (United States)

    Klein, Eran; Brown, Tim; Sample, Matthew; Truitt, Anjali R; Goering, Sara

    2015-01-01

    Neural devices now under development stand to interact with and alter the human brain in ways that may challenge standard notions of identity, normality, authority, responsibility, privacy and justice.

  6. Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro.

    Science.gov (United States)

    Aleksandrova, M A; Poltavtseva, R A; Marei, M V; Sukhikh, G T

    2016-05-01

    Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed.

  7. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders.

    Science.gov (United States)

    Kos, Claire; van Tol, Marie-José; Marsman, Jan-Bernard C; Knegtering, Henderikus; Aleman, André

    2016-10-01

    Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution. Copyright © 2016. Published by Elsevier Ltd.

  8. A Sensitive and Specific Neural Signature for Picture-Induced Negative Affect.

    Directory of Open Access Journals (Sweden)

    Luke J Chang

    2015-06-01

    Full Text Available Neuroimaging has identified many correlates of emotion but has not yet yielded brain representations predictive of the intensity of emotional experiences in individuals. We used machine learning to identify a sensitive and specific signature of emotional responses to aversive images. This signature predicted the intensity of negative emotion in individual participants in cross validation (n =121 and test (n = 61 samples (high-low emotion = 93.5% accuracy. It was unresponsive to physical pain (emotion-pain = 92% discriminative accuracy, demonstrating that it is not a representation of generalized arousal or salience. The signature was comprised of mesoscale patterns spanning multiple cortical and subcortical systems, with no single system necessary or sufficient for predicting experience. Furthermore, it was not reducible to activity in traditional "emotion-related" regions (e.g., amygdala, insula or resting-state networks (e.g., "salience," "default mode". Overall, this work identifies differentiable neural components of negative emotion and pain, providing a basis for new, brain-based taxonomies of affective processes.

  9. Focusing on neuronal cell-type specific mechanisms for brain circuit organization, function and dysfunction

    Institute of Scientific and Technical Information of China (English)

    Lu Li

    2017-01-01

    Mammalian brain circuits consist of dynamically interconnected neurons with characteristic morphology, physiology, connectivity and genetics which are often called neuronal cell types. Neuronal cell types have been considered as building blocks of brain circuits, but knowledge of how neuron types or subtypes connect to and interact with each other to perform neural computation is still lacking. Such mechanistic insights are critical not only to our understanding of normal brain functions, such as perception, motion and cognition, but also to brain disorders including Alzheimer's disease, Schizophrenia and epilepsy, to name a few. Thus it is necessary to carry out systematic and standardized studies on neuronal cell-type specific mechanisms for brain circuit organization and function, which will provide good opportunities to bridge basic and clinical research. Here based on recent technology advancements, we discuss the strategy to target and manipulate specific populations of neuronsin vivo to provide unique insights on how neuron types or subtypes behave, interact, and generate emergent properties in a fully connected brain network. Our approach is highlighted by combining transgenic animal models, targeted electrophysiology and imaging with robotics, thus complete and standardized mapping ofin vivo properties of genetically defined neuron populations can be achieved in transgenic mouse models, which will facilitate the development of novel therapeutic strategies for brain disorders.

  10. The Burden of Binge and Heavy Drinking on the Brain: Effects on Adolescent and Young Adult Neural Structure and Function

    Directory of Open Access Journals (Sweden)

    Anita Cservenka

    2017-06-01

    Full Text Available Introduction: Adolescence and young adulthood are periods of continued biological and psychosocial maturation. Thus, there may be deleterious effects of consuming large quantities of alcohol on neural development and associated cognition during this time. The purpose of this mini review is to highlight neuroimaging research that has specifically examined the effects of binge and heavy drinking on adolescent and young adult brain structure and function.Methods: We review cross-sectional and longitudinal studies of young binge and heavy drinkers that have examined brain structure (e.g., gray and white matter volume, cortical thickness, white matter microstructure and investigated brain response using functional magnetic resonance imaging (fMRI.Results: Binge and heavy-drinking adolescents and young adults have systematically thinner and lower volume in prefrontal cortex and cerebellar regions, and attenuated white matter development. They also show elevated brain activity in fronto-parietal regions during working memory, verbal learning, and inhibitory control tasks. In response to alcohol cues, relative to controls or light-drinking individuals, binge and heavy drinkers show increased neural response mainly in mesocorticolimbic regions, including the striatum, anterior cingulate cortex (ACC, hippocampus, and amygdala. Mixed findings are present in risky decision-making tasks, which could be due to large variation in task design and analysis.Conclusions: These findings suggest altered neural structure and activity in binge and heavy-drinking youth may be related to the neurotoxic effects of consuming alcohol in large quantities during a highly plastic neurodevelopmental period, which could result in neural reorganization, and increased risk for developing an alcohol use disorder (AUD.

  11. Polarity-specific high-level information propagation in neural networks.

    Science.gov (United States)

    Lin, Yen-Nan; Chang, Po-Yen; Hsiao, Pao-Yueh; Lo, Chung-Chuan

    2014-01-01

    Analyzing the connectome of a nervous system provides valuable information about the functions of its subsystems. Although much has been learned about the architectures of neural networks in various organisms by applying analytical tools developed for general networks, two distinct and functionally important properties of neural networks are often overlooked. First, neural networks are endowed with polarity at the circuit level: Information enters a neural network at input neurons, propagates through interneurons, and leaves via output neurons. Second, many functions of nervous systems are implemented by signal propagation through high-level pathways involving multiple and often recurrent connections rather than by the shortest paths between nodes. In the present study, we analyzed two neural networks: the somatic nervous system of Caenorhabditis elegans (C. elegans) and the partial central complex network of Drosophila, in light of these properties. Specifically, we quantified high-level propagation in the vertical and horizontal directions: the former characterizes how signals propagate from specific input nodes to specific output nodes and the latter characterizes how a signal from a specific input node is shared by all output nodes. We found that the two neural networks are characterized by very efficient vertical and horizontal propagation. In comparison, classic small-world networks show a trade-off between vertical and horizontal propagation; increasing the rewiring probability improves the efficiency of horizontal propagation but worsens the efficiency of vertical propagation. Our result provides insights into how the complex functions of natural neural networks may arise from a design that allows them to efficiently transform and combine input signals.

  12. Could LC-NE-Dependent Adjustment of Neural Gain Drive Functional Brain Network Reorganization?

    Directory of Open Access Journals (Sweden)

    Carole Guedj

    2017-01-01

    Full Text Available The locus coeruleus-norepinephrine (LC-NE system is thought to act at synaptic, cellular, microcircuit, and network levels to facilitate cognitive functions through at least two different processes, not mutually exclusive. Accordingly, as a reset signal, the LC-NE system could trigger brain network reorganizations in response to salient information in the environment and/or adjust the neural gain within its target regions to optimize behavioral responses. Here, we provide evidence of the co-occurrence of these two mechanisms at the whole-brain level, in resting-state conditions following a pharmacological stimulation of the LC-NE system. We propose that these two mechanisms are interdependent such that the LC-NE-dependent adjustment of the neural gain inferred from the clustering coefficient could drive functional brain network reorganizations through coherence in the gamma rhythm. Via the temporal dynamic of gamma-range band-limited power, the release of NE could adjust the neural gain, promoting interactions only within the neuronal populations whose amplitude envelopes are correlated, thus making it possible to reorganize neuronal ensembles, functional networks, and ultimately, behavioral responses. Thus, our proposal offers a unified framework integrating the putative influence of the LC-NE system on both local- and long-range adjustments of brain dynamics underlying behavioral flexibility.

  13. Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning

    Directory of Open Access Journals (Sweden)

    Aldo A. M. Lima

    2013-01-01

    Full Text Available OBJECTIVE: To identify the impact of supplemental zinc, vitamin A, and glutamine, alone or in combination, on long-term cognitive outcomes among Brazilian shantytown children with low median height-for-age z-scores. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in children aged three months to nine years old from the urban shanty compound community of Fortaleza, Brazil. Demographic and anthropometric information was assessed. The random treatment groups available for cognitive testing (total of 167 children were: (1 placebo, n = 25; (2 glutamine, n = 23; (3 zinc, n = 18; (4 vitamin A, n = 19; (5 glutamine+zinc, n = 20; (6 glutamine+vitamin A, n = 21; (7 zinc+vitamin A, n = 23; and (8 glutamine+zinc+vitamin A, n = 18. Neuropsychological tests were administered for the cognitive domains of non-verbal intelligence and abstraction, psychomotor speed, verbal memory and recall ability, and semantic and phonetic verbal fluency. Statistical analyses were performed using SPSS, version 16.0. ClinicalTrials.gov: NCT00133406. RESULTS: Girls receiving a combination of glutamine, zinc, and vitamin A had higher mean age-adjusted verbal learning scores than girls receiving only placebo (9.5 versus 6.4, p = 0.007 and girls receiving zinc+vitamin A (9.5 versus 6.5, p = 0.006. Similar group differences were not found between male study children. CONCLUSIONS: The findings suggest that combination therapy offers a sex-specific advantage on tests of verbal learning, similar to that seen among female patients following traumatic brain injury.

  14. Partially flexible MEMS neural probe composed of polyimide and sucrose gel for reducing brain damage during and after implantation

    International Nuclear Information System (INIS)

    Jeon, Myounggun; Yoon, Eui-Sung; Cho, Il-Joo; Cho, Jeiwon; Jung, Dahee; Kim, Yun Kyung; Shin, Sehyun

    2014-01-01

    This paper presents a flexible microelectromechanical systems (MEMS) neural probe that minimizes neuron damage and immune response, suitable for chronic recording applications. MEMS neural probes with various features such as high electrode densities have been actively investigated for neuron stimulation and recording to study brain functions. However, successful recording of neural signals in chronic application using rigid silicon probes still remains challenging because of cell death and macrophages accumulated around the electrodes over time from continuous brain movement. Thus, in this paper, we propose a new flexible MEMS neural probe that consists of two segments: a polyimide-based, flexible segment for connection and a rigid segment composed of thin silicon for insertion. While the flexible connection segment is designed to reduce the long-term chronic neuron damage, the thin insertion segment is designed to minimize the brain damage during the insertion process. The proposed flexible neural probe was successfully fabricated using the MEMS process on a silicon on insulator wafer. For a successful insertion, a biodegradable sucrose gel is coated on the flexible segment to temporarily increase the probe stiffness to prevent buckling. After the insertion, the sucrose gel dissolves inside the brain exposing the polyimide probe. By performing an insertion test, we confirm that the flexible probe has enough stiffness. In addition, by monitoring immune responses and brain histology, we successfully demonstrate that the proposed flexible neural probe incurs fivefold less neural damage than that incurred by a conventional silicon neural probe. Therefore, the presented flexible neural probe is a promising candidate for recording stable neural signals for long-time chronic applications. (paper)

  15. Uncovering the neuroanatomical correlates of cognitive, affective and conative theory of mind in paediatric traumatic brain injury: a neural systems perspective.

    Science.gov (United States)

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Hearps, Stephen J; Beauchamp, Miriam H; Yeates, Keith O; Anderson, Vicki A

    2017-09-01

    Deficits in theory of mind (ToM) are common after neurological insult acquired in the first and second decade of life, however the contribution of large-scale neural networks to ToM deficits in children with brain injury is unclear. Using paediatric traumatic brain injury (TBI) as a model, this study investigated the sub-acute effect of paediatric traumatic brain injury on grey-matter volume of three large-scale, domain-general brain networks (the Default Mode Network, DMN; the Central Executive Network, CEN; and the Salience Network, SN), as well as two domain-specific neural networks implicated in social-affective processes (the Cerebro-Cerebellar Mentalizing Network, CCMN and the Mirror Neuron/Empathy Network, MNEN). We also evaluated prospective structure-function relationships between these large-scale neural networks and cognitive, affective and conative ToM. 3D T1- weighted magnetic resonance imaging sequences were acquired sub-acutely in 137 children [TBI: n = 103; typically developing (TD) children: n = 34]. All children were assessed on measures of ToM at 24-months post-injury. Children with severe TBI showed sub-acute volumetric reductions in the CCMN, SN, MNEN, CEN and DMN, as well as reduced grey-matter volumes of several hub regions of these neural networks. Volumetric reductions in the CCMN and several of its hub regions, including the cerebellum, predicted poorer cognitive ToM. In contrast, poorer affective and conative ToM were predicted by volumetric reductions in the SN and MNEN, respectively. Overall, results suggest that cognitive, affective and conative ToM may be prospectively predicted by individual differences in structure of different neural systems-the CCMN, SN and MNEN, respectively. The prospective relationship between cerebellar volume and cognitive ToM outcomes is a novel finding in our paediatric brain injury sample and suggests that the cerebellum may play a role in the neural networks important for ToM. These findings are

  16. Neural responses to macronutrients: hedonic and homeostatic mechanisms.

    Science.gov (United States)

    Tulloch, Alastair J; Murray, Susan; Vaicekonyte, Regina; Avena, Nicole M

    2015-05-01

    The brain responds to macronutrients via intricate mechanisms. We review how the brain's neural systems implicated in homeostatic control of feeding and hedonic responses are influenced by the ingestion of specific types of food. We discuss how these neural systems are dysregulated in preclinical models of obesity. Findings from these studies can increase our understanding of overeating and, perhaps in some cases, the development of obesity. In addition, a greater understanding of the neural circuits affected by the consumption of specific macronutrients, and by obesity, might lead to new treatments and strategies for preventing unhealthy weight gain. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Mapping the brain's orchestration during speech comprehension: task-specific facilitation of regional synchrony in neural networks

    Directory of Open Access Journals (Sweden)

    Keil Andreas

    2004-10-01

    Full Text Available Abstract Background How does the brain convert sounds and phonemes into comprehensible speech? In the present magnetoencephalographic study we examined the hypothesis that the coherence of electromagnetic oscillatory activity within and across brain areas indicates neurophysiological processes linked to speech comprehension. Results Amplitude-modulated (sinusoidal 41.5 Hz auditory verbal and nonverbal stimuli served to drive steady-state oscillations in neural networks involved in speech comprehension. Stimuli were presented to 12 subjects in the following conditions (a an incomprehensible string of words, (b the same string of words after being introduced as a comprehensible sentence by proper articulation, and (c nonverbal stimulations that included a 600-Hz tone, a scale, and a melody. Coherence, defined as correlated activation of magnetic steady state fields across brain areas and measured as simultaneous activation of current dipoles in source space (Minimum-Norm-Estimates, increased within left- temporal-posterior areas when the sound string was perceived as a comprehensible sentence. Intra-hemispheric coherence was larger within the left than the right hemisphere for the sentence (condition (b relative to all other conditions, and tended to be larger within the right than the left hemisphere for nonverbal stimuli (condition (c, tone and melody relative to the other conditions, leading to a more pronounced hemispheric asymmetry for nonverbal than verbal material. Conclusions We conclude that coherent neuronal network activity may index encoding of verbal information on the sentence level and can be used as a tool to investigate auditory speech comprehension.

  18. Replicable Expansion and Differentiation of Neural Precursors from Adult Canine Skin

    Directory of Open Access Journals (Sweden)

    Thomas Duncan

    2017-08-01

    Full Text Available Repopulation of brain circuits by neural precursors is a potential therapeutic strategy for neurodegenerative disorders; however, choice of cell is critical. Previously, we introduced a two-step culture system that generates a high yield of neural precursors from small samples of adult canine skin. Here, we probe their gene and protein expression profiles in comparison with dermal fibroblasts and brain-derived neural stem cells and characterize their neuronal potential. To date, we have produced >50 skin-derived neural precursor (SKN lines. SKNs can be cultured in a highly replicable fashion and uniformly express a panel of identifying markers. Upon differentiation, they self-upregulate neural specification genes, generating neurons with basic electrophysiological functionality. This unique population of neural precursors, derived from mature skin, overcomes many of the practical issues that have limited clinical translation of alternative cell types. Easily accessible, neuronally committed, and patient specific, SKNs may have potential for the treatment of brain disorders.

  19. Involvement of Atm and Trp53 in neural cell loss due to Terf2 inactivation during mouse brain development.

    Science.gov (United States)

    Kim, Jusik; Choi, Inseo; Lee, Youngsoo

    2017-11-01

    Maintenance of genomic integrity is one of the critical features for proper neurodevelopment and inhibition of neurological diseases. The signals from both ATM and ATR to TP53 are well-known mechanisms to remove neural cells with DNA damage during neurogenesis. Here we examined the involvement of Atm and Atr in genomic instability due to Terf2 inactivation during mouse brain development. Selective inactivation of Terf2 in neural progenitors induced apoptosis, resulting in a complete loss of the brain structure. This neural loss was rescued partially in both Atm and Trp53 deficiency, but not in an Atr-deficient background in the mouse. Atm inactivation resulted in incomplete brain structures, whereas p53 deficiency led to the formation of multinucleated giant neural cells and the disruption of the brain structure. These giant neural cells disappeared in Lig4 deficiency. These data demonstrate ATM and TP53 are important for the maintenance of telomere homeostasis and the surveillance of telomere dysfunction during neurogenesis.

  20. Multiscale neural connectivity during human sensory processing in the brain

    Science.gov (United States)

    Maksimenko, Vladimir A.; Runnova, Anastasia E.; Frolov, Nikita S.; Makarov, Vladimir V.; Nedaivozov, Vladimir; Koronovskii, Alexey A.; Pisarchik, Alexander; Hramov, Alexander E.

    2018-05-01

    Stimulus-related brain activity is considered using wavelet-based analysis of neural interactions between occipital and parietal brain areas in alpha (8-12 Hz) and beta (15-30 Hz) frequency bands. We show that human sensory processing related to the visual stimuli perception induces brain response resulted in different ways of parieto-occipital interactions in these bands. In the alpha frequency band the parieto-occipital neuronal network is characterized by homogeneous increase of the interaction between all interconnected areas both within occipital and parietal lobes and between them. In the beta frequency band the occipital lobe starts to play a leading role in the dynamics of the occipital-parietal network: The perception of visual stimuli excites the visual center in the occipital area and then, due to the increase of parieto-occipital interactions, such excitation is transferred to the parietal area, where the attentional center takes place. In the case when stimuli are characterized by a high degree of ambiguity, we find greater increase of the interaction between interconnected areas in the parietal lobe due to the increase of human attention. Based on revealed mechanisms, we describe the complex response of the parieto-occipital brain neuronal network during the perception and primary processing of the visual stimuli. The results can serve as an essential complement to the existing theory of neural aspects of visual stimuli processing.

  1. Zinc content of selected tissues and taste perception in rats fed zinc deficient and zinc adequate rations

    International Nuclear Information System (INIS)

    Boeckner, L.S.; Kies, C.

    1986-01-01

    The objective of the study was to determine the effects of feeding zinc sufficient and zinc deficient rations on taste sensitivity and zinc contents of selected organs in rats. The 36 Sprague-Dawley male weanling rats were divided into 2 groups and fed zinc deficient or zinc adequate rations. The animals were subjected to 4 trial periods in which a choice of deionized distilled water or a solution of quinine sulfate at 1.28 x 10 -6 was given. A randomized schedule for rat sacrifice was used. No differences were found between zinc deficient and zinc adequate rats in taste preference aversion scores for quinine sulfate in the first three trial periods; however, in the last trial period rats in the zinc sufficient group drank somewhat less water containing quinine sulfate as a percentage of total water consumption than did rats fed the zinc deficient ration. Significantly higher zinc contents of kidney, brain and parotid salivary glands were seen in zinc adequate rats compared to zinc deficient rats at the end of the study. However, liver and tongue zinc levels were lower for both groups at the close of the study than were those of rats sacrificed at the beginning of the study

  2. Decoding of Human Movements Based on Deep Brain Local Field Potentials Using Ensemble Neural Networks

    Directory of Open Access Journals (Sweden)

    Mohammad S. Islam

    2017-01-01

    Full Text Available Decoding neural activities related to voluntary and involuntary movements is fundamental to understanding human brain motor circuits and neuromotor disorders and can lead to the development of neuromotor prosthetic devices for neurorehabilitation. This study explores using recorded deep brain local field potentials (LFPs for robust movement decoding of Parkinson’s disease (PD and Dystonia patients. The LFP data from voluntary movement activities such as left and right hand index finger clicking were recorded from patients who underwent surgeries for implantation of deep brain stimulation electrodes. Movement-related LFP signal features were extracted by computing instantaneous power related to motor response in different neural frequency bands. An innovative neural network ensemble classifier has been proposed and developed for accurate prediction of finger movement and its forthcoming laterality. The ensemble classifier contains three base neural network classifiers, namely, feedforward, radial basis, and probabilistic neural networks. The majority voting rule is used to fuse the decisions of the three base classifiers to generate the final decision of the ensemble classifier. The overall decoding performance reaches a level of agreement (kappa value at about 0.729±0.16 for decoding movement from the resting state and about 0.671±0.14 for decoding left and right visually cued movements.

  3. Neural underpinnings of music: the polyrhythmic brain.

    Science.gov (United States)

    Vuust, Peter; Gebauer, Line K; Witek, Maria A G

    2014-01-01

    Musical rhythm, consisting of apparently abstract intervals of accented temporal events, has the remarkable ability to move our minds and bodies. Why do certain rhythms make us want to tap our feet, bop our heads or even get up and dance? And how does the brain process rhythmically complex rhythms during our experiences of music? In this chapter, we describe some common forms of rhythmic complexity in music and propose that the theory of predictive coding can explain how rhythm and rhythmic complexity are processed in the brain. We also consider how this theory may reveal why we feel so compelled by rhythmic tension in music. First, musical-theoretical and neuroscientific frameworks of rhythm are presented, in which rhythm perception is conceptualized as an interaction between what is heard ('rhythm') and the brain's anticipatory structuring of music ('the meter'). Second, three different examples of tension between rhythm and meter in music are described: syncopation, polyrhythm and groove. Third, we present the theory of predictive coding of music, which posits a hierarchical organization of brain responses reflecting fundamental, survival-related mechanisms associated with predicting future events. According to this theory, perception and learning is manifested through the brain's Bayesian minimization of the error between the input to the brain and the brain's prior expectations. Fourth, empirical studies of neural and behavioral effects of syncopation, polyrhythm and groove will be reported, and we propose how these studies can be seen as special cases of the predictive coding theory. Finally, we argue that musical rhythm exploits the brain's general principles of anticipation and propose that pleasure from musical rhythm may be a result of such anticipatory mechanisms.

  4. Neural activity and emotional processing following military deployment: Effects of mild traumatic brain injury and posttraumatic stress disorder.

    Science.gov (United States)

    Zuj, Daniel V; Felmingham, Kim L; Palmer, Matthew A; Lawrence-Wood, Ellie; Van Hooff, Miranda; Lawrence, Andrew J; Bryant, Richard A; McFarlane, Alexander C

    2017-11-01

    Posttraumatic Stress Disorder (PTSD) and mild traumatic brain injury (mTBI) are common comorbidities during military deployment that affect emotional brain processing, yet few studies have examined the independent effects of mTBI and PTSD. The purpose of this study was to examine distinct differences in neural responses to emotional faces in mTBI and PTSD. Twenty-one soldiers reporting high PTSD symptoms were compared to 21 soldiers with low symptoms, and 16 soldiers who reported mTBI-consistent injury and symptoms were compared with 16 soldiers who did not sustain an mTBI. Participants viewed emotional face expressions while their neural activity was recorded (via event-related potentials) prior to and following deployment. The high-PTSD group displayed increased P1 and P2 amplitudes to threatening faces at post-deployment compared to the low-PTSD group. In contrast, the mTBI group displayed reduced face-specific processing (N170 amplitude) to all facial expressions compared to the no-mTBI group. Here, we identified distinctive neural patterns of emotional face processing, with attentional biases towards threatening faces in PTSD, and reduced emotional face processing in mTBI. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Deep Neural Networks: A New Framework for Modeling Biological Vision and Brain Information Processing.

    Science.gov (United States)

    Kriegeskorte, Nikolaus

    2015-11-24

    Recent advances in neural network modeling have enabled major strides in computer vision and other artificial intelligence applications. Human-level visual recognition abilities are coming within reach of artificial systems. Artificial neural networks are inspired by the brain, and their computations could be implemented in biological neurons. Convolutional feedforward networks, which now dominate computer vision, take further inspiration from the architecture of the primate visual hierarchy. However, the current models are designed with engineering goals, not to model brain computations. Nevertheless, initial studies comparing internal representations between these models and primate brains find surprisingly similar representational spaces. With human-level performance no longer out of reach, we are entering an exciting new era, in which we will be able to build biologically faithful feedforward and recurrent computational models of how biological brains perform high-level feats of intelligence, including vision.

  6. Neural, not gonadal, origin of brain sex differences in a gynandromorphic finch

    OpenAIRE

    Agate, Robert J.; Grisham, William; Wade, Juli; Mann, Suzanne; Wingfield, John; Schanen, Carolyn; Palotie, Aarno; Arnold, Arthur P.

    2003-01-01

    In mammals and birds, sex differences in brain function and disease are thought to derive exclusively from sex differences in gonadal hormone secretions. For example, testosterone in male mammals acts during fetal and neonatal life to cause masculine neural development. However, male and female brain cells also differ in genetic sex; thus, sex chromosome genes acting within cells could contribute to sex differences in cell function. We analyzed the sexual phenotype of the brain of a rare gyna...

  7. Rodent Zic Genes in Neural Network Wiring.

    Science.gov (United States)

    Herrera, Eloísa

    2018-01-01

    The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.

  8. Effects of category-specific costs on neural systems for perceptual decision-making.

    Science.gov (United States)

    Fleming, Stephen M; Whiteley, Louise; Hulme, Oliver J; Sahani, Maneesh; Dolan, Raymond J

    2010-06-01

    Perceptual judgments are often biased by prospective losses, leading to changes in decision criteria. Little is known about how and where sensory evidence and cost information interact in the brain to influence perceptual categorization. Here we show that prospective losses systematically bias the perception of noisy face-house images. Asymmetries in category-specific cost were associated with enhanced blood-oxygen-level-dependent signal in a frontoparietal network. We observed selective activation of parahippocampal gyrus for changes in category-specific cost in keeping with the hypothesis that loss functions enact a particular task set that is communicated to visual regions. Across subjects, greater shifts in decision criteria were associated with greater activation of the anterior cingulate cortex (ACC). Our results support a hypothesis that costs bias an intermediate representation between perception and action, expressed via general effects on frontal cortex, and selective effects on extrastriate cortex. These findings indicate that asymmetric costs may affect a neural implementation of perceptual decision making in a similar manner to changes in category expectation, constituting a step toward accounting for how prospective losses are flexibly integrated with sensory evidence in the brain.

  9. Transport and metabolism at blood-brain interfaces and in neural cells: relevance to bilirubin-induced encephalopathy

    Directory of Open Access Journals (Sweden)

    Silvia eGazzin

    2012-05-01

    Full Text Available Bilirubin, the end-product of heme catabolism, circulates in non pathological plasma mostly as a protein-bound species. When bilirubin concentration builds up, the free fraction of the molecule increases. Unbound bilirubin then diffuses across blood-brain interfaces into the brain, where it accumulates and exerts neurotoxic effects. In this classical view of bilirubin neurotoxicity, blood-brain interfaces act merely as structural barriers impeding the penetration of the pigment-bound carrier protein, and neural cells are considered as passive targets of its toxicity. Yet, the role of blood-brain interfaces in the occurrence of bilirubin encephalopathy appears more complex than being simple barriers to the diffusion of bilirubin, and neural cells such as astrocytes and neurons can play an active role in controlling the balance between the neuroprotective and neurotoxic effects of bilirubin. This article reviews the emerging in vivo and in vitro data showing that transport and metabolic detoxification mechanisms at the blood-brain and blood-CSF barriers may modulate bilirubin flux across both cellular interfaces, and that these protective functions can be affected in chronic hyperbilirubinemia. Then the in vivo and in vitro arguments in favor of the physiological antioxidant function of intracerebral bilirubin are presented, as well as with the potential role of transporters such as ABCC-1 and metabolizing enzymes such as cytochromes P-450 in setting the cerebral cell- and structure-specific toxicity of bilirubin following hyperbilirubinemia. The relevance of these data to the pathophysiology of bilirubin-induced neurological diseases is discussed.

  10. Analysis of neural activity in human motor cortex -- Towards brain machine interface system

    Science.gov (United States)

    Secundo, Lavi

    The discovery of directional tuned neurons in the primary motor cortex has advanced motor research in several domains. For instance, in the area of brain machine interface (BMI), researchers have exploited the robust characteristic of tuned motor neurons to allow monkeys to learn control of various machines. In the first chapter of this work we examine whether this phenomena can be observed using the less invasive method of recording electrocorticographic signals (ECoG) from the surface of a human's brain. Our findings reveal that individual ECoG channels contain complex movement information about the neuronal population. While some ECoG channels are tuned to hand movement direction (direction specific channels), others are associated to movement but do not contain information regarding movement direction (non-direction specific channels). More specifically, directionality can vary temporally and by frequency within one channel. In addition, a handful of channels contain no significant information regarding movement at all. These findings strongly suggest that directional and non-directional regions of cortex can be identified with ECoG and provide solutions to decoding movement at the signal resolution provided by ECoG. In the second chapter we examine the influence of movement context on movement reconstruction accuracy. We recorded neuronal signals recorded from electro-corticography (ECoG) during performance of cued- and self-initiated movements. ECoG signals were used to train a reconstruction algorithm to reconstruct continuous hand movement. We found that both cued- and self-initiated movements could be reconstructed with similar accuracy from the ECoG data. However, while an algorithm trained on the cued task could reconstruct performance on a subsequent cued trial, it failed to reconstruct self-initiated arm movement. The same task-specificity was observed when the algorithm was trained with self-initiated movement data and tested on the cued task. Thus

  11. Soman poisoning increases neural progenitor proliferation and induces long-term glial activation in mouse brain

    International Nuclear Information System (INIS)

    Collombet, Jean-Marc; Four, Elise; Bernabe, Denis; Masqueliez, Catherine; Burckhart, Marie-France; Baille, Valerie; Baubichon, Dominique; Lallement, Guy

    2005-01-01

    To date, only short-term glial reaction has been extensively studied following soman or other warfare neurotoxicant poisoning. In a context of cell therapy by neural progenitor engraftment to repair brain damage, the long-term effect of soman on glial reaction and neural progenitor division was analyzed in the present study. The effect of soman poisoning was estimated in mouse brains at various times ranging from 1 to 90 days post-poisoning. Using immunochemistry and dye staining techniques (hemalun-eosin staining), the number of degenerating neurons, the number of dividing neural progenitors, and microglial, astroglial or oligodendroglial cell activation were studied. Soman poisoning led to rapid and massive (post-soman day 1) death of mature neurons as assessed by hemalun-eosin staining. Following this acute poisoning phase, a weak toxicity effect on mature neurons was still observed for a period of 1 month after poisoning. A massive short-termed microgliosis peaked on day 3 post-poisoning. Delayed astrogliosis was observed from 3 to 90 days after soman poisoning, contributing to glial scar formation. On the other hand, oligodendroglial cells or their precursors were practically unaffected by soman poisoning. Interestingly, neural progenitors located in the subgranular zone of the dentate gyrus (SGZ) or in the subventricular zone (SVZ) of the brain survived soman poisoning. Furthermore, soman poisoning significantly increased neural progenitor proliferation in both SGZ and SVZ brain areas on post-soman day 3 or day 8, respectively. This increased proliferation rate was detected up to 1 month after poisoning

  12. Inter-progenitor pool wiring: An evolutionarily conserved strategy that expands neural circuit diversity.

    Science.gov (United States)

    Suzuki, Takumi; Sato, Makoto

    2017-11-15

    Diversification of neuronal types is key to establishing functional variations in neural circuits. The first critical step to generate neuronal diversity is to organize the compartmental domains of developing brains into spatially distinct neural progenitor pools. Neural progenitors in each pool then generate a unique set of diverse neurons through specific spatiotemporal specification processes. In this review article, we focus on an additional mechanism, 'inter-progenitor pool wiring', that further expands the diversity of neural circuits. After diverse types of neurons are generated in one progenitor pool, a fraction of these neurons start migrating toward a remote brain region containing neurons that originate from another progenitor pool. Finally, neurons of different origins are intermingled and eventually form complex but precise neural circuits. The developing cerebral cortex of mammalian brains is one of the best examples of inter-progenitor pool wiring. However, Drosophila visual system development has revealed similar mechanisms in invertebrate brains, suggesting that inter-progenitor pool wiring is an evolutionarily conserved strategy that expands neural circuit diversity. Here, we will discuss how inter-progenitor pool wiring is accomplished in mammalian and fly brain systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Sex-specific neural circuits of emotion regulation in the centromedial amygdala.

    Science.gov (United States)

    Wu, Yan; Li, Huandong; Zhou, Yuan; Yu, Jian; Zhang, Yuanchao; Song, Ming; Qin, Wen; Yu, Chunshui; Jiang, Tianzi

    2016-03-23

    Sex-related differences in emotion regulation (ER) in the frequency power distribution within the human amygdala, a brain region involved in emotion processing, have been reported. However, how sex differences in ER are manifested in the brain networks which are seeded on the amygdala subregions is unclear. The goal of this study was to investigate this issue from a brain network perspective. Utilizing resting-state functional connectivity (RSFC) analysis, we found that the sex-specific functional connectivity patterns associated with ER trait level were only seeded in the centromedial amygdala (CM). Women with a higher trait-level ER had a stronger negative RSFC between the right CM and the medial superior frontal gyrus (mSFG), and stronger positive RSFC between the right CM and the anterior insula (AI) and the superior temporal gyrus (STG). But men with a higher trait-level ER was associated with weaker negative RSFC of the right CM-mSFG and positive RSFCs of the right CM-left AI, right CM-right AI/STG, and right CM-left STG. These results provide evidence for the sex-related effects in ER based on CM and indicate that men and women may differ in the neural circuits associated with emotion representation and integration.

  14. Murine cytomegalovirus infection of neural stem cells alters neurogenesis in the developing brain.

    Directory of Open Access Journals (Sweden)

    Manohar B Mutnal

    2011-01-01

    Full Text Available Congenital cytomegalovirus (CMV brain infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital brain infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV and the pattern of injury to the developing brain.We used our MCMV infection model and a multi-color flow cytometry approach to quantify the effect of viral infection on the developing brain, identifying specific target cells and the consequent effect on neurogenesis. In this study, we show that neural stem cells (NSCs and neuronal precursor cells are the principal target cells for MCMV in the developing brain. In addition, viral infection was demonstrated to cause a loss of NSCs expressing CD133 and nestin. We also showed that infection of neonates leads to subsequent abnormal brain development as indicated by loss of CD24(hi cells that incorporated BrdU. This neonatal brain infection was also associated with altered expression of Oct4, a multipotency marker; as well as down regulation of the neurotrophins BDNF and NT3, which are essential to regulate the birth and differentiation of neurons during normal brain development. Finally, we report decreased expression of doublecortin, a marker to identify young neurons, following viral brain infection.MCMV brain infection of newborn mice causes significant loss of NSCs, decreased proliferation of neuronal precursor cells, and marked loss of young neurons.

  15. Brain tumor segmentation using holistically nested neural networks in MRI images.

    Science.gov (United States)

    Zhuge, Ying; Krauze, Andra V; Ning, Holly; Cheng, Jason Y; Arora, Barbara C; Camphausen, Kevin; Miller, Robert W

    2017-10-01

    Gliomas are rapidly progressive, neurologically devastating, largely fatal brain tumors. Magnetic resonance imaging (MRI) is a widely used technique employed in the diagnosis and management of gliomas in clinical practice. MRI is also the standard imaging modality used to delineate the brain tumor target as part of treatment planning for the administration of radiation therapy. Despite more than 20 yr of research and development, computational brain tumor segmentation in MRI images remains a challenging task. We are presenting a novel method of automatic image segmentation based on holistically nested neural networks that could be employed for brain tumor segmentation of MRI images. Two preprocessing techniques were applied to MRI images. The N4ITK method was employed for correction of bias field distortion. A novel landmark-based intensity normalization method was developed so that tissue types have a similar intensity scale in images of different subjects for the same MRI protocol. The holistically nested neural networks (HNN), which extend from the convolutional neural networks (CNN) with a deep supervision through an additional weighted-fusion output layer, was trained to learn the multiscale and multilevel hierarchical appearance representation of the brain tumor in MRI images and was subsequently applied to produce a prediction map of the brain tumor on test images. Finally, the brain tumor was obtained through an optimum thresholding on the prediction map. The proposed method was evaluated on both the Multimodal Brain Tumor Image Segmentation (BRATS) Benchmark 2013 training datasets, and clinical data from our institute. A dice similarity coefficient (DSC) and sensitivity of 0.78 and 0.81 were achieved on 20 BRATS 2013 training datasets with high-grade gliomas (HGG), based on a two-fold cross-validation. The HNN model built on the BRATS 2013 training data was applied to ten clinical datasets with HGG from a locally developed database. DSC and sensitivity of

  16. Neural control of finger movement via intracortical brain-machine interface

    Science.gov (United States)

    Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Bullard, A. J.; Tat, D. M.; Nu, C. S.; Vaskov, A.; Nason, S. R.; Thompson, D. E.; Bentley, J. N.; Patil, P. G.; Chestek, C. A.

    2017-12-01

    Objective. Intracortical brain-machine interfaces (BMIs) are a promising source of prosthesis control signals for individuals with severe motor disabilities. Previous BMI studies have primarily focused on predicting and controlling whole-arm movements; precise control of hand kinematics, however, has not been fully demonstrated. Here, we investigate the continuous decoding of precise finger movements in rhesus macaques. Approach. In order to elicit precise and repeatable finger movements, we have developed a novel behavioral task paradigm which requires the subject to acquire virtual fingertip position targets. In the physical control condition, four rhesus macaques performed this task by moving all four fingers together in order to acquire a single target. This movement was equivalent to controlling the aperture of a power grasp. During this task performance, we recorded neural spikes from intracortical electrode arrays in primary motor cortex. Main results. Using a standard Kalman filter, we could reconstruct continuous finger movement offline with an average correlation of ρ  =  0.78 between actual and predicted position across four rhesus macaques. For two of the monkeys, this movement prediction was performed in real-time to enable direct brain control of the virtual hand. Compared to physical control, neural control performance was slightly degraded; however, the monkeys were still able to successfully perform the task with an average target acquisition rate of 83.1%. The monkeys’ ability to arbitrarily specify fingertip position was also quantified using an information throughput metric. During brain control task performance, the monkeys achieved an average 1.01 bits s-1 throughput, similar to that achieved in previous studies which decoded upper-arm movements to control computer cursors using a standard Kalman filter. Significance. This is, to our knowledge, the first demonstration of brain control of finger-level fine motor skills. We believe

  17. Organization of the sleep-related neural systems in the brain of the minke whale (Balaenoptera acutorostrata).

    Science.gov (United States)

    Dell, Leigh-Anne; Karlsson, Karl Ae; Patzke, Nina; Spocter, Muhammad A; Siegel, Jerome M; Manger, Paul R

    2016-07-01

    The current study analyzed the nuclear organization of the neural systems related to the control and regulation of sleep and wake in the basal forebrain, diencephalon, midbrain, and pons of the minke whale, a mysticete cetacean. While odontocete cetaceans sleep in an unusual manner, with unihemispheric slow wave sleep (USWS) and suppressed REM sleep, it is unclear whether the mysticete whales show a similar sleep pattern. Previously, we detailed a range of features in the odontocete brain that appear to be related to odontocete-type sleep, and here present our analysis of these features in the minke whale brain. All neural elements involved in sleep regulation and control found in bihemispheric sleeping mammals and the harbor porpoise were present in the minke whale, with no specific nuclei being absent, and no novel nuclei being present. This qualitative similarity relates to the cholinergic, noradrenergic, serotonergic and orexinergic systems, and the GABAergic elements of these nuclei. Quantitative analysis revealed that the numbers of pontine cholinergic (274,242) and noradrenergic (203,686) neurons, and hypothalamic orexinergic neurons (277,604), are markedly higher than other large-brained bihemispheric sleeping mammals. Small telencephalic commissures (anterior, corpus callosum, and hippocampal), an enlarged posterior commissure, supernumerary pontine cholinergic and noradrenergic cells, and an enlarged peripheral division of the dorsal raphe nuclear complex of the minke whale, all indicate that the suite of neural characteristics thought to be involved in the control of USWS and the suppression of REM in the odontocete cetaceans are present in the minke whale. J. Comp. Neurol. 524:2018-2035, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  18. Automatic Semantic Segmentation of Brain Gliomas from MRI Images Using a Deep Cascaded Neural Network.

    Science.gov (United States)

    Cui, Shaoguo; Mao, Lei; Jiang, Jingfeng; Liu, Chang; Xiong, Shuyu

    2018-01-01

    Brain tumors can appear anywhere in the brain and have vastly different sizes and morphology. Additionally, these tumors are often diffused and poorly contrasted. Consequently, the segmentation of brain tumor and intratumor subregions using magnetic resonance imaging (MRI) data with minimal human interventions remains a challenging task. In this paper, we present a novel fully automatic segmentation method from MRI data containing in vivo brain gliomas. This approach can not only localize the entire tumor region but can also accurately segment the intratumor structure. The proposed work was based on a cascaded deep learning convolutional neural network consisting of two subnetworks: (1) a tumor localization network (TLN) and (2) an intratumor classification network (ITCN). The TLN, a fully convolutional network (FCN) in conjunction with the transfer learning technology, was used to first process MRI data. The goal of the first subnetwork was to define the tumor region from an MRI slice. Then, the ITCN was used to label the defined tumor region into multiple subregions. Particularly, ITCN exploited a convolutional neural network (CNN) with deeper architecture and smaller kernel. The proposed approach was validated on multimodal brain tumor segmentation (BRATS 2015) datasets, which contain 220 high-grade glioma (HGG) and 54 low-grade glioma (LGG) cases. Dice similarity coefficient (DSC), positive predictive value (PPV), and sensitivity were used as evaluation metrics. Our experimental results indicated that our method could obtain the promising segmentation results and had a faster segmentation speed. More specifically, the proposed method obtained comparable and overall better DSC values (0.89, 0.77, and 0.80) on the combined (HGG + LGG) testing set, as compared to other methods reported in the literature. Additionally, the proposed approach was able to complete a segmentation task at a rate of 1.54 seconds per slice.

  19. Non-invasive determination of the absorption coefficient of the brain from time-resolved reflectance using a neural network

    International Nuclear Information System (INIS)

    Jaeger, Marion; Kienle, Alwin

    2011-01-01

    We investigated the performance of a neural network for derivation of the absorption coefficient of the brain from simulated non-invasive time-resolved reflectance measurements on the head. A five-layered geometry was considered assuming that the optical properties (except the absorption coefficient of the brain) and the thickness of all layers were known with an uncertainty. A solution of the layered diffusion equation was used to train the neural network. We determined the absorption coefficient of the brain with an RMS error of <6% from reflectance data at a single distance calculated by diffusion theory. By applying the neural network to reflectance curves obtained from Monte Carlo simulations, similar errors were found. (note)

  20. Rebalancing the Addicted Brain: Oxytocin Interference with the Neural Substrates of Addiction.

    Science.gov (United States)

    Bowen, Michael T; Neumann, Inga D

    2017-12-01

    Drugs that act on the brain oxytocin (OXT) system may provide a much-needed treatment breakthrough for substance-use disorders. Targeting the brain OXT system has the potential to treat addiction to all major classes of addictive substance and to intervene across all stages of the addiction cycle. Emerging evidence suggests that OXT is able to interfere with such a wide range of addictive behaviours for such a wide range of addictive substances by rebalancing core neural systems that become dysregulated over the course of addiction. By improving our understanding of these interactions between OXT and the neural substrates of addiction, we will not only improve our understanding of addiction, but also our ability to effectively treat these devastating disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. A new method for brain tumor detection using the Bhattacharyya similarity coefficient, color conversions and neural network

    Directory of Open Access Journals (Sweden)

    Bahman Mansori

    2015-10-01

    Full Text Available Background: Magnetic resonance imaging (MRI is widely applied for examination and diagnosis of brain tumors based on its advantages of high resolution in detecting the soft tissues and especially of its harmless radiation damages to human bodies. The goal of the processing of images is automatic segmentation of brain edema and tumors, in different dimensions of the magnetic resonance images. Methods: The proposed method is based on the unsupervised method which discovers the tumor region, if there is any, by analyzing the similarities between two hemispheres and computes the image size of the goal function based on Bhattacharyya coefficient which is used in the next stage to detect the tumor region or some part of it. In this stage, for reducing the color variation, the gray brain image is segmented, then it is turned to gray again. The self-organizing map (SOM neural network is used the segmented brain image is colored and finally the tumor is detected by matching the detected region and the colored image. This method is proposed to analyze MRI images for discovering brain tumors, and done in Bu Ali Sina University, Hamedan, Iran, in 2014. Results: The results for 30 randomly selected images from data bank of MRI center in Hamedan was compared with manually segmentation of experts. The results showed that, our proposed method had the accuracy of more than 94% at Jaccard similarity index (JSI, 97% at Dice similarity score (DSS, and 98% and 99% at two measures of specificity and sensitivity. Conclusion: The experimental results showed that it was satisfactory and can be used in automatic separation of tumor from normal brain tissues and therefore it can be used in practical applications. The results showed that the use of SOM neural network to classify useful magnetic resonance imaging of the brain and demonstrated a good performance.

  2. Neural Networks

    International Nuclear Information System (INIS)

    Smith, Patrick I.

    2003-01-01

    information [2]. Each one of these cells acts as a simple processor. When individual cells interact with one another, the complex abilities of the brain are made possible. In neural networks, the input or data are processed by a propagation function that adds up the values of all the incoming data. The ending value is then compared with a threshold or specific value. The resulting value must exceed the activation function value in order to become output. The activation function is a mathematical function that a neuron uses to produce an output referring to its input value. [8] Figure 1 depicts this process. Neural networks usually have three components an input, a hidden, and an output. These layers create the end result of the neural network. A real world example is a child associating the word dog with a picture. The child says dog and simultaneously looks a picture of a dog. The input is the spoken word ''dog'', the hidden is the brain processing, and the output will be the category of the word dog based on the picture. This illustration describes how a neural network functions

  3. Taurine Induces Proliferation of Neural Stem Cells and Synapse Development in the Developing Mouse Brain

    Science.gov (United States)

    Shivaraj, Mattu Chetana; Marcy, Guillaume; Low, Guoliang; Ryu, Jae Ryun; Zhao, Xianfeng; Rosales, Francisco J.; Goh, Eyleen L. K.

    2012-01-01

    Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems. PMID:22916184

  4. Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders.

    Science.gov (United States)

    Zhang, Jie; Cheng, Wei; Liu, Zhaowen; Zhang, Kai; Lei, Xu; Yao, Ye; Becker, Benjamin; Liu, Yicen; Kendrick, Keith M; Lu, Guangming; Feng, Jianfeng

    2016-08-01

    ratio of intra- to inter-community structural connectivity. Application of the mesoscale variability measure to multicentre datasets of three mental disorders and matched controls involving 1180 subjects reveals that those regions demonstrating extreme, i.e. highest/lowest variability in controls are most liable to change in mental disorders. Specifically, we draw attention to the identification of diametrically opposing patterns of variability changes between schizophrenia and attention deficit hyperactivity disorder/autism. Regions of the default-mode network demonstrate lower variability in patients with schizophrenia, but high variability in patients with autism/attention deficit hyperactivity disorder, compared with respective controls. In contrast, subcortical regions, especially the thalamus, show higher variability in schizophrenia patients, but lower variability in patients with attention deficit hyperactivity disorder. The changes in variability of these regions are also closely related to symptom scores. Our work provides insights into the dynamic organization of the resting brain and how it changes in brain disorders. The nodal variability measure may also be potentially useful as a predictor for learning and neural rehabilitation. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Molecular Mechanisms of Synaptic Specificity: Spotlight on Hippocampal and Cerebellar Synapse Organizers.

    Science.gov (United States)

    Park, Dongseok; Bae, Sungwon; Yoon, Taek Han; Ko, Jaewon

    2018-04-18

    Synapses and neural circuits form with exquisite specificity during brain development to allow the precise and appropriate flow of neural information. Although this property of synapses and neural circuits has been extensively investigated for more than a century, molecular mechanisms underlying this property are only recently being unveiled. Recent studies highlight several classes of cell-surface proteins as organizing hubs in building structural and functional architectures of specific synapses and neural circuits. In the present minireview, we discuss recent findings on various synapse organizers that confer the distinct properties of specific synapse types and neural circuit architectures in mammalian brains, with a particular focus on the hippocampus and cerebellum.

  6. Neural correlates of socioeconomic status in the developing human brain.

    Science.gov (United States)

    Noble, Kimberly G; Houston, Suzanne M; Kan, Eric; Sowell, Elizabeth R

    2012-07-01

    Socioeconomic disparities in childhood are associated with remarkable differences in cognitive and socio-emotional development during a time when dramatic changes are occurring in the brain. Yet, the neurobiological pathways through which socioeconomic status (SES) shapes development remain poorly understood. Behavioral evidence suggests that language, memory, social-emotional processing, and cognitive control exhibit relatively large differences across SES. Here we investigated whether volumetric differences could be observed across SES in several neural regions that support these skills. In a sample of 60 socioeconomically diverse children, highly significant SES differences in regional brain volume were observed in the hippocampus and the amygdala. In addition, SES × age interactions were observed in the left superior temporal gyrus and left inferior frontal gyrus, suggesting increasing SES differences with age in these regions. These results were not explained by differences in gender, race or IQ. Likely mechanisms include differences in the home linguistic environment and exposure to stress, which may serve as targets for intervention at a time of high neural plasticity. © 2012 Blackwell Publishing Ltd.

  7. Dynamics of scene representations in the human brain revealed by magnetoencephalography and deep neural networks

    Science.gov (United States)

    Cichy, Radoslaw Martin; Khosla, Aditya; Pantazis, Dimitrios; Oliva, Aude

    2017-01-01

    Human scene recognition is a rapid multistep process evolving over time from single scene image to spatial layout processing. We used multivariate pattern analyses on magnetoencephalography (MEG) data to unravel the time course of this cortical process. Following an early signal for lower-level visual analysis of single scenes at ~100 ms, we found a marker of real-world scene size, i.e. spatial layout processing, at ~250 ms indexing neural representations robust to changes in unrelated scene properties and viewing conditions. For a quantitative model of how scene size representations may arise in the brain, we compared MEG data to a deep neural network model trained on scene classification. Representations of scene size emerged intrinsically in the model, and resolved emerging neural scene size representation. Together our data provide a first description of an electrophysiological signal for layout processing in humans, and suggest that deep neural networks are a promising framework to investigate how spatial layout representations emerge in the human brain. PMID:27039703

  8. Neural-Network Control Of Prosthetic And Robotic Hands

    Science.gov (United States)

    Buckley, Theresa M.

    1991-01-01

    Electronic neural networks proposed for use in controlling robotic and prosthetic hands and exoskeletal or glovelike electromechanical devices aiding intact but nonfunctional hands. Specific to patient, who activates grasping motion by voice command, by mechanical switch, or by myoelectric impulse. Patient retains higher-level control, while lower-level control provided by neural network analogous to that of miniature brain. During training, patient teaches miniature brain to perform specialized, anthropomorphic movements unique to himself or herself.

  9. An introduction to neural networks surgery, a field of neuromodulation which is based on advances in neural networks science and digitised brain imaging.

    Science.gov (United States)

    Sakas, D E; Panourias, I G; Simpson, B A

    2007-01-01

    Operative Neuromodulation is the field of altering electrically or chemically the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks and produce therapeutic effects. The present article reviews relevant literature on procedures or devices applied either in contact with the cerebral cortex or cranial nerves or in deep sites inside the brain in order to treat various refractory neurological conditions such as: a) chronic pain (facial, somatic, deafferentation, phantom limb), b) movement disorders (Parkinson's disease, dystonia, Tourette syndrome), c) epilepsy, d) psychiatric disease, e) hearing deficits, and f) visual loss. These data indicate that in operative neuromodulation, a new field emerges that is based on neural networks research and on advances in digitised stereometric brain imaging which allow precise localisation of cerebral neural networks and their relay stations; this field can be described as Neural networks surgery because it aims to act extrinsically or intrinsically on neural networks and to alter therapeutically the neural signal transmission with the use of implantable electrical or electronic devices. The authors also review neurotechnology literature relevant to neuroengineering, nanotechnologies, brain computer interfaces, hybrid cultured probes, neuromimetics, neuroinformatics, neurocomputation, and computational neuromodulation; the latter field is dedicated to the study of the biophysical and mathematical characteristics of electrochemical neuromodulation. The article also brings forward particularly interesting lines of research such as the carbon nanofibers electrode arrays for simultaneous electrochemical recording and stimulation, closed-loop systems for responsive neuromodulation, and the intracortical electrodes for restoring hearing or vision. The present review of cerebral neuromodulatory procedures highlights the transition from the

  10. Deep convolutional neural networks for annotating gene expression patterns in the mouse brain.

    Science.gov (United States)

    Zeng, Tao; Li, Rongjian; Mukkamala, Ravi; Ye, Jieping; Ji, Shuiwang

    2015-05-07

    Profiling gene expression in brain structures at various spatial and temporal scales is essential to understanding how genes regulate the development of brain structures. The Allen Developing Mouse Brain Atlas provides high-resolution 3-D in situ hybridization (ISH) gene expression patterns in multiple developing stages of the mouse brain. Currently, the ISH images are annotated with anatomical terms manually. In this paper, we propose a computational approach to annotate gene expression pattern images in the mouse brain at various structural levels over the course of development. We applied deep convolutional neural network that was trained on a large set of natural images to extract features from the ISH images of developing mouse brain. As a baseline representation, we applied invariant image feature descriptors to capture local statistics from ISH images and used the bag-of-words approach to build image-level representations. Both types of features from multiple ISH image sections of the entire brain were then combined to build 3-D, brain-wide gene expression representations. We employed regularized learning methods for discriminating gene expression patterns in different brain structures. Results show that our approach of using convolutional model as feature extractors achieved superior performance in annotating gene expression patterns at multiple levels of brain structures throughout four developing ages. Overall, we achieved average AUC of 0.894 ± 0.014, as compared with 0.820 ± 0.046 yielded by the bag-of-words approach. Deep convolutional neural network model trained on natural image sets and applied to gene expression pattern annotation tasks yielded superior performance, demonstrating its transfer learning property is applicable to such biological image sets.

  11. The Neural Basis of and a Common Neural Circuitry in Different Types of Pro-social Behavior

    Directory of Open Access Journals (Sweden)

    Jun Luo

    2018-06-01

    Full Text Available Pro-social behaviors are voluntary behaviors that benefit other people or society as a whole, such as charitable donations, cooperation, trust, altruistic punishment, and fairness. These behaviors have been widely described through non self-interest decision-making in behavioral experimental studies and are thought to be increased by social preference motives. Importantly, recent studies using a combination of neuroimaging and brain stimulation, designed to reveal the neural mechanisms of pro-social behaviors, have found that a wide range of brain areas, specifically the prefrontal cortex, anterior insula, anterior cingulate cortex, and amygdala, are correlated or causally related with pro-social behaviors. In this review, we summarize the research on the neural basis of various kinds of pro-social behaviors and describe a common shared neural circuitry of these pro-social behaviors. We introduce several general ways in which experimental economics and neuroscience can be combined to develop important contributions to understanding social decision-making and pro-social behaviors. Future research should attempt to explore the neural circuitry between the frontal lobes and deeper brain areas.

  12. BrainCrafter: An investigation into human-based neural network engineering

    DEFF Research Database (Denmark)

    Piskur, J.; Greve, P.; Togelius, J.

    2015-01-01

    This paper presents the online application Brain-Crafter, in which users can manually build artificial neural networks (ANNs) to control a robot in a maze environment. Users can either start to construct networks from scratch or elaborate on networks created by other users. In particular, Brain......Crafter was designed to study how good we as humans are at building ANNs for control problems and if collaborating with other users can facilitate this process. The results in this paper show that (1) some users were in fact able to successfully construct ANNs that solve the navigation tasks, (2) collaboration between...

  13. Construction of an interatomic potential for zinc oxide surfaces by high-dimensional neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Artrith, Nongnuch; Morawietz, Tobias; Behler, Joerg [Lehrstuhl fuer Theoretische Chemie, Ruhr-Universitaet Bochum, D-44780 Bochum (Germany)

    2011-07-01

    Zinc oxide (ZnO) is a technologically important material with many applications, e.g. in heterogeneous catalysis. For theoretical studies of the structural properties of ZnO surfaces, defects, and crystal structures it is necessary to simulate large systems over long time-scales with sufficient accuracy. Often, the required system size is not accessible by computationally rather demanding density-functional theory (DFT) calculations. Recently, artificial Neural Networks (NN) trained to first principles data have shown to provide accurate potential-energy surfaces (PESs) for condensed systems. We present the construction and analysis of a NN PES for ZnO. The structural and energetic properties of bulk ZnO and ZnO surfaces are investigated using this potential and compared to DFT calculations.

  14. Ion Channels and Zinc: Mechanisms of Neurotoxicity and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Deborah R. Morris

    2012-01-01

    Full Text Available Ionotropic glutamate receptors, such as NMDA, AMPA and kainate receptors, are ligand-gated ion channels that mediate much of the excitatory neurotransmission in the brain. Not only do these receptors bind glutamate, but they are also regulated by and facilitate the postsynaptic uptake of the trace metal zinc. This paper discusses the role of the excitotoxic influx and accumulation of zinc, the mechanisms responsible for its cytotoxicity, and a number of disorders of the central nervous system that have been linked to these neuronal ion channels and zinc toxicity including ischemic brain injury, traumatic brain injury, and epilepsy.

  15. Deep Convolutional Neural Networks for Multi-Modality Isointense Infant Brain Image Segmentation

    Science.gov (United States)

    Zhang, Wenlu; Li, Rongjian; Deng, Houtao; Wang, Li; Lin, Weili; Ji, Shuiwang; Shen, Dinggang

    2015-01-01

    The segmentation of infant brain tissue images into white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) plays an important role in studying early brain development in health and disease. In the isointense stage (approximately 6–8 months of age), WM and GM exhibit similar levels of intensity in both T1 and T2 MR images, making the tissue segmentation very challenging. Only a small number of existing methods have been designed for tissue segmentation in this isointense stage; however, they only used a single T1 or T2 images, or the combination of T1 and T2 images. In this paper, we propose to use deep convolutional neural networks (CNNs) for segmenting isointense stage brain tissues using multi-modality MR images. CNNs are a type of deep models in which trainable filters and local neighborhood pooling operations are applied alternatingly on the raw input images, resulting in a hierarchy of increasingly complex features. Specifically, we used multimodality information from T1, T2, and fractional anisotropy (FA) images as inputs and then generated the segmentation maps as outputs. The multiple intermediate layers applied convolution, pooling, normalization, and other operations to capture the highly nonlinear mappings between inputs and outputs. We compared the performance of our approach with that of the commonly used segmentation methods on a set of manually segmented isointense stage brain images. Results showed that our proposed model significantly outperformed prior methods on infant brain tissue segmentation. In addition, our results indicated that integration of multi-modality images led to significant performance improvement. PMID:25562829

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

    Science.gov (United States)

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

    2011-08-01

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

  17. Presenilins are required for maintenance of neural stem cells in the developing brain

    Directory of Open Access Journals (Sweden)

    Kim Woo-Young

    2008-01-01

    Full Text Available Abstract The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to generate presenilin conditional double knockout (PS cDKO mice, in which expression of both presenilins is inactivated in neural progenitor cells (NPC or neural stem cells and their derivative neurons and glia beginning at embryonic day 11 (E11. In PS cDKO mice, dividing NPCs labeled by BrdU are decreased in number beginning at E13.5. By E15.5, fewer than 20% of NPCs remain in PS cDKO mice. The depletion of NPCs is accompanied by severe morphological defects and hemorrhages in the PS cDKO embryonic brain. Interkinetic nuclear migration of NPCs is also disrupted in PS cDKO embryos, as evidenced by displacement of S-phase and M-phase nuclei in the ventricular zone of the telencephalon. Furthermore, the depletion of neural progenitor cells in PS cDKO embryos is due to NPCs exiting cell cycle and differentiating into neurons rather than reentering cell cycle between E13.5 and E14.5 following PS inactivation in most NPCs. The length of cell cycle, however, is unchanged in PS cDKO embryos. Expression of Notch target genes, Hes1 and Hes5, is significantly decreased in PS cDKO brains, whereas Dll1 expression is up-regulated, indicating that Notch signaling is effectively blocked by PS inactivation. These findings demonstrate that presenilins are essential for neural progenitor cells to re-enter cell cycle and thus ensure proper expansion of neural progenitor pool during embryonic neural development.

  18. Statistical physics, neural networks, brain studies

    International Nuclear Information System (INIS)

    Toulouse, G.

    1999-01-01

    An overview of some aspects of a vast domain, located at the crossroads of physics, biology and computer science is presented: (1) During the last fifteen years, physicists advancing along various pathways have come into contact with biology (computational neurosciences) and engineering (formal neural nets). (2) This move may actually be viewed as one component in a larger picture. A prominent trend of recent years, observable over many countries, has been the establishment of interdisciplinary centers devoted to the study of: cognitive sciences; natural and artificial intelligence; brain, mind and behaviour; perception and action; learning and memory; robotics; man-machine communication, etc. What are the promising lines of development? What opportunities for physicists? An attempt will be made to address such questions and related issues

  19. Simultaneous in vivo recording of local brain temperature and electrophysiological signals with a novel neural probe

    Science.gov (United States)

    Fekete, Z.; Csernai, M.; Kocsis, K.; Horváth, Á. C.; Pongrácz, A.; Barthó, P.

    2017-06-01

    Objective. Temperature is an important factor for neural function both in normal and pathological states, nevertheless, simultaneous monitoring of local brain temperature and neuronal activity has not yet been undertaken. Approach. In our work, we propose an implantable, calibrated multimodal biosensor that facilitates the complex investigation of thermal changes in both cortical and deep brain regions, which records multiunit activity of neuronal populations in mice. The fabricated neural probe contains four electrical recording sites and a platinum temperature sensor filament integrated on the same probe shaft within a distance of 30 µm from the closest recording site. The feasibility of the simultaneous functionality is presented in in vivo studies. The probe was tested in the thalamus of anesthetized mice while manipulating the core temperature of the animals. Main results. We obtained multiunit and local field recordings along with measurement of local brain temperature with accuracy of 0.14 °C. Brain temperature generally followed core body temperature, but also showed superimposed fluctuations corresponding to epochs of increased local neural activity. With the application of higher currents, we increased the local temperature by several degrees without observable tissue damage between 34-39 °C. Significance. The proposed multifunctional tool is envisioned to broaden our knowledge on the role of the thermal modulation of neuronal activity in both cortical and deeper brain regions.

  20. The modulation of neural gain facilitates a transition between functional segregation and integration in the brain.

    Science.gov (United States)

    Shine, James M; Aburn, Matthew J; Breakspear, Michael; Poldrack, Russell A

    2018-01-29

    Cognitive function relies on a dynamic, context-sensitive balance between functional integration and segregation in the brain. Previous work has proposed that this balance is mediated by global fluctuations in neural gain by projections from ascending neuromodulatory nuclei. To test this hypothesis in silico, we studied the effects of neural gain on network dynamics in a model of large-scale neuronal dynamics. We found that increases in neural gain directed the network through an abrupt dynamical transition, leading to an integrated network topology that was maximal in frontoparietal 'rich club' regions. This gain-mediated transition was also associated with increased topological complexity, as well as increased variability in time-resolved topological structure, further highlighting the potential computational benefits of the gain-mediated network transition. These results support the hypothesis that neural gain modulation has the computational capacity to mediate the balance between integration and segregation in the brain. © 2018, Shine et al.

  1. Conductive nanogel-interfaced neural microelectrode arrays with electrically controlled in-situ delivery of manganese ions enabling high-resolution MEMRI for synchronous neural tracing with deep brain stimulation.

    Science.gov (United States)

    Huang, Wei-Chen; Lo, Yu-Chih; Chu, Chao-Yi; Lai, Hsin-Yi; Chen, You-Yin; Chen, San-Yuan

    2017-04-01

    Chronic brain stimulation has become a promising physical therapy with increased efficacy and efficiency in the treatment of neurodegenerative diseases. The application of deep brain electrical stimulation (DBS) combined with manganese-enhanced magnetic resonance imaging (MEMRI) provides an unbiased representation of the functional anatomy, which shows the communication between areas of the brain responding to the therapy. However, it is challenging for the current system to provide a real-time high-resolution image because the incorporated MnCl 2 solution through microinjection usually results in image blurring or toxicity due to the uncontrollable diffusion of Mn 2+ . In this study, we developed a new type of conductive nanogel-based neural interface composed of amphiphilic chitosan-modified poly(3,4 -ethylenedioxythiophene) (PMSDT) that can exhibit biomimic structural/mechanical properties and ionic/electrical conductivity comparable to that of Au. More importantly, the PMSDT enables metal-ligand bonding with Mn 2+ ions, so that the system can release Mn 2+ ions rather than MnCl 2 solution directly and precisely controlled by electrical stimulation (ES) to achieve real-time high-resolution MEMRI. With the integration of PMSDT nanogel-based coating in polyimide-based microelectrode arrays, the post-implantation DBS enables frequency-dependent MR imaging in vivo, as well as small focal imaging in response to channel site-specific stimulation on the implant. The MR imaging of the implanted brain treated with 5-min electrical stimulation showed a thalamocortical neuronal pathway after 36 h, confirming the effective activation of a downstream neuronal circuit following DBS. By eliminating the susceptibility to artifact and toxicity, this system, in combination with a MR-compatible implant and a bio-compliant neural interface, provides a harmless and synchronic functional anatomy for DBS. The study demonstrates a model of MEMRI-functionalized DBS based on functional

  2. Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells.

    Science.gov (United States)

    Yan, Yiping; Shin, Soojung; Jha, Balendu Shekhar; Liu, Qiuyue; Sheng, Jianting; Li, Fuhai; Zhan, Ming; Davis, Janine; Bharti, Kapil; Zeng, Xianmin; Rao, Mahendra; Malik, Nasir; Vemuri, Mohan C

    2013-11-01

    Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, labor-intensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

  3. Stimulus specificity of a steady-state visual-evoked potential-based brain-computer interface

    Science.gov (United States)

    Ng, Kian B.; Bradley, Andrew P.; Cunnington, Ross

    2012-06-01

    The mechanisms of neural excitation and inhibition when given a visual stimulus are well studied. It has been established that changing stimulus specificity such as luminance contrast or spatial frequency can alter the neuronal activity and thus modulate the visual-evoked response. In this paper, we study the effect that stimulus specificity has on the classification performance of a steady-state visual-evoked potential-based brain-computer interface (SSVEP-BCI). For example, we investigate how closely two visual stimuli can be placed before they compete for neural representation in the cortex and thus influence BCI classification accuracy. We characterize stimulus specificity using the four stimulus parameters commonly encountered in SSVEP-BCI design: temporal frequency, spatial size, number of simultaneously displayed stimuli and their spatial proximity. By varying these quantities and measuring the SSVEP-BCI classification accuracy, we are able to determine the parameters that provide optimal performance. Our results show that superior SSVEP-BCI accuracy is attained when stimuli are placed spatially more than 5° apart, with size that subtends at least 2° of visual angle, when using a tagging frequency of between high alpha and beta band. These findings may assist in deciding the stimulus parameters for optimal SSVEP-BCI design.

  4. Neural Correlates of Expert Behavior During a Domain-Specific Attentional Cueing Task in Badminton Players.

    Science.gov (United States)

    Wang, Chun-Hao; Tu, Kuo-Cheng

    2017-06-01

    The present study aimed to investigate the neural correlates associated with sports expertise during a domain-specific task in badminton players. We compared event-related potentials activity from collegiate male badminton players and a set of matched athletic controls when they performed a badminton-specific attentional cueing task in which the uncertainty and validity were manipulated. The data showed that, regardless of cue type, the badminton players had faster responses along with greater P3 amplitudes than the athletic controls on the task. Specifically, the contingent negative variation amplitude was smaller for the players than for the controls in the condition involving higher uncertainty. Such an effect, however, was absent in the condition with lower uncertainty. We conclude that expertise in sports is associated with proficient modulation of brain activity during cognitive and motor preparation, as well as response execution, when performing a task related to an individual's specific sport domain.

  5. Optimal feedback control successfully explains changes in neural modulations during experiments with brain-machine interfaces

    Directory of Open Access Journals (Sweden)

    Miriam eZacksenhouse

    2015-05-01

    Full Text Available Recent experiments with brain-machine-interfaces (BMIs indicate that the extent of neural modulations increased abruptly upon starting to operate the interface, and especially after the monkey stopped moving its hand. In contrast, neural modulations that are correlated with the kinematics of the movement remained relatively unchanged. Here we demonstrate that similar changes are produced by simulated neurons that encode the relevant signals generated by an optimal feedback controller during simulated BMI experiments. The optimal feedback controller relies on state estimation that integrates both visual and proprioceptive feedback with prior estimations from an internal model. The processing required for optimal state estimation and control were conducted in the state-space, and neural recording was simulated by modeling two populations of neurons that encode either only the estimated state or also the control signal. Spike counts were generated as realizations of doubly stochastic Poisson processes with linear tuning curves. The model successfully reconstructs the main features of the kinematics and neural activity during regular reaching movements. Most importantly, the activity of the simulated neurons successfully reproduces the observed changes in neural modulations upon switching to brain control. Further theoretical analysis and simulations indicate that increasing the process noise during normal reaching movement results in similar changes in neural modulations. Thus we conclude that the observed changes in neural modulations during BMI experiments can be attributed to increasing process noise associated with the imperfect BMI filter, and, more directly, to the resulting increase in the variance of the encoded signals associated with state estimation and the required control signal.

  6. Optimal feedback control successfully explains changes in neural modulations during experiments with brain-machine interfaces.

    Science.gov (United States)

    Benyamini, Miri; Zacksenhouse, Miriam

    2015-01-01

    Recent experiments with brain-machine-interfaces (BMIs) indicate that the extent of neural modulations increased abruptly upon starting to operate the interface, and especially after the monkey stopped moving its hand. In contrast, neural modulations that are correlated with the kinematics of the movement remained relatively unchanged. Here we demonstrate that similar changes are produced by simulated neurons that encode the relevant signals generated by an optimal feedback controller during simulated BMI experiments. The optimal feedback controller relies on state estimation that integrates both visual and proprioceptive feedback with prior estimations from an internal model. The processing required for optimal state estimation and control were conducted in the state-space, and neural recording was simulated by modeling two populations of neurons that encode either only the estimated state or also the control signal. Spike counts were generated as realizations of doubly stochastic Poisson processes with linear tuning curves. The model successfully reconstructs the main features of the kinematics and neural activity during regular reaching movements. Most importantly, the activity of the simulated neurons successfully reproduces the observed changes in neural modulations upon switching to brain control. Further theoretical analysis and simulations indicate that increasing the process noise during normal reaching movement results in similar changes in neural modulations. Thus, we conclude that the observed changes in neural modulations during BMI experiments can be attributed to increasing process noise associated with the imperfect BMI filter, and, more directly, to the resulting increase in the variance of the encoded signals associated with state estimation and the required control signal.

  7. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders

    Directory of Open Access Journals (Sweden)

    Kristen J. Brennand

    2015-12-01

    Full Text Available As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

  8. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    International Nuclear Information System (INIS)

    Sun, Jinqiao; Sha, Bin; Zhou, Wenhao; Yang, Yi

    2010-01-01

    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  9. Stage-specific and age-dependent profiles of zinc, copper, manganese, and selenium in rat seminiferous tubules

    International Nuclear Information System (INIS)

    Homma-Takeda, S.; Nishimura, Y.; Watanabe, Y.; Imaseki, H.; Yukawa, M.

    2004-01-01

    Stage-specific and age-dependent profiles of zinc, copper, manganese, and selenium in testis were examined in Wistar rats by both inductively coupled argon plasma-mass spectrometry (ICP-MS) with a microdissection technique and in situ elemental imaging of micro-PIXE analysis. The young adult animals (10 weeks old) contained higher levels of zinc and manganese in the seminiferous tubules at stages VII-VIII than stages XI through VI and IX-X and the levels were higher than those of the immature and old animals. Copper and selenium levels at stages VII-VIII of the young adult animals were also higher than those of the immature and old animals. In stages VII and VIII, zinc was higher in the central area of the seminiferous epithelium, where spermatozoa were localized, demonstrating a cell-specific property. (author)

  10. Identification and target prediction of miRNAs specifically expressed in rat neural tissue

    Directory of Open Access Journals (Sweden)

    Tu Kang

    2009-05-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are a large group of RNAs that play important roles in regulating gene expression and protein translation. Several studies have indicated that some miRNAs are specifically expressed in human, mouse and zebrafish tissues. For example, miR-1 and miR-133 are specifically expressed in muscles. Tissue-specific miRNAs may have particular functions. Although previous studies have reported the presence of human, mouse and zebrafish tissue-specific miRNAs, there have been no detailed reports of rat tissue-specific miRNAs. In this study, Home-made rat miRNA microarrays which established in our previous study were used to investigate rat neural tissue-specific miRNAs, and mapped their target genes in rat tissues. This study will provide information for the functional analysis of these miRNAs. Results In order to obtain as complete a picture of specific miRNA expression in rat neural tissues as possible, customized miRNA microarrays with 152 selected miRNAs from miRBase were used to detect miRNA expression in 14 rat tissues. After a general clustering analysis, 14 rat tissues could be clearly classified into neural and non-neural tissues based on the obtained expression profiles with p values Conclusion Our work provides a global view of rat neural tissue-specific miRNA profiles and a target map of miRNAs, which is expected to contribute to future investigations of miRNA regulatory mechanisms in neural systems.

  11. Effect of sibutramine on 5-hydroxyindole acetic acid levels and selected oxidative biomarkers on brain regions of female rats in the presence of zinc.

    Science.gov (United States)

    Guzmán, David C; García, Ernestina H; Mejía, Gerardo B; Olguín, Hugo J; Jiménez, Francisca T; Soto, Erick B; Del Angel, Daniel S; Aparicio, Liliana C

    2012-05-01

    A number of drugs, like sibutramine, which are used clinically in weight control, act on serotonergic metabolism. However, their relation with zinc and free radical (FR) production in central nervous system remains unknown. This study aimed to evaluate the effect of sibutramine and zinc on FR production. Female Wistar rats (about 250 g) were used in this study. The animals received 400 μg/kg of zinc and 10 mg/kg of sibutramine intraperitoneally every 36 hr for 15 days. At the end of the study, the rats were killed and their brains used for the measurement of lipid peroxidation thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH), hydrogen peroxide (H(2) O(2) ), calcium and 5-hydroxyindole acetic acid (5-HIAA) levels, all by means of validated methods. Corporal weight and food consumption were found to be decreased in the zinc/sibutramine group. TBARS decreased in cortex, hemispheres and medulla oblongata. GSH decreased in cortex, hemispheres and cerebellum in the sibutramine group. Zinc given alone and in combination with sibutramine decreased H(2) O(2) concentration in cortex, hemispheres and cerebellum but increased calcium and 5-HIAA concentration in all brain regions. Our results suggest that sibutramine and zinc are associated with weight loss, an effect that was more pronounced in the group treated with both drugs. Reduction in oxidative stress may be involved in these effects. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  12. Hierarchical Neural Representation of Dreamed Objects Revealed by Brain Decoding with Deep Neural Network Features.

    Science.gov (United States)

    Horikawa, Tomoyasu; Kamitani, Yukiyasu

    2017-01-01

    Dreaming is generally thought to be generated by spontaneous brain activity during sleep with patterns common to waking experience. This view is supported by a recent study demonstrating that dreamed objects can be predicted from brain activity during sleep using statistical decoders trained with stimulus-induced brain activity. However, it remains unclear whether and how visual image features associated with dreamed objects are represented in the brain. In this study, we used a deep neural network (DNN) model for object recognition as a proxy for hierarchical visual feature representation, and DNN features for dreamed objects were analyzed with brain decoding of fMRI data collected during dreaming. The decoders were first trained with stimulus-induced brain activity labeled with the feature values of the stimulus image from multiple DNN layers. The decoders were then used to decode DNN features from the dream fMRI data, and the decoded features were compared with the averaged features of each object category calculated from a large-scale image database. We found that the feature values decoded from the dream fMRI data positively correlated with those associated with dreamed object categories at mid- to high-level DNN layers. Using the decoded features, the dreamed object category could be identified at above-chance levels by matching them to the averaged features for candidate categories. The results suggest that dreaming recruits hierarchical visual feature representations associated with objects, which may support phenomenal aspects of dream experience.

  13. Elemental concentrations and tracer uptake behavior of manganese, zinc, and selenium in brain of normal mice during development

    International Nuclear Information System (INIS)

    Tarohda, Tohru; Yabushita, Yuko; Kanayama, Yousuke; Amano, Ryohei; Enomoto, Shuichi

    2001-01-01

    Concentrations and uptake behavior of manganese (Mn), zinc (Zn), and selenium (Se) in mouse brain were studied by a multitracer technique, neutron activation analysis and autoradiography. Comparative concentrations on Mn, Zn, and Se and tracer uptake behavior of 54 Mn, 65 Zn, and 75 Se were examined in brains of 1-, 4-, 8-, 21-, and 56-day-old mice, and evaluated in terms of brain concentration (parts per million, ppm) and brain uptake rate (the radioactivity percentage of injected dose per gram of brain, %dose/g), respectively. As a result, the brain concentrations of Mn increased with growth, although those of Se and Zn did not change. On the other hand, the uptakes of the three tracers by brains of 1-day-old mice were much higher than those of older ones. Using radioactive 54 Mn as a single tracer, autoradiography was examined to determine the Mn uptake regional distribution in brains of 1-, 8-, and 21-day-old mice, and a higher regional uptake of Mn by the cerebral cortex, hippocampus, thalamus and hypothalamus in brains of young mice was observed. (author)

  14. Transcranial magnetic stimulation and connectivity mapping: tools for studying the neural bases of brain disorders.

    Science.gov (United States)

    Hampson, M; Hoffman, R E

    2010-01-01

    There has been an increasing emphasis on characterizing pathophysiology underlying psychiatric and neurological disorders in terms of altered neural connectivity and network dynamics. Transcranial magnetic stimulation (TMS) provides a unique opportunity for investigating connectivity in the human brain. TMS allows researchers and clinicians to directly stimulate cortical regions accessible to electromagnetic coils positioned on the scalp. The induced activation can then propagate through long-range connections to other brain areas. Thus, by identifying distal regions activated during TMS, researchers can infer connectivity patterns in the healthy human brain and can examine how those patterns may be disrupted in patients with different brain disorders. Conversely, connectivity maps derived using neuroimaging methods can identify components of a dysfunctional network. Nodes in this dysfunctional network accessible as targets for TMS by virtue of their proximity to the scalp may then permit TMS-induced alterations of components of the network not directly accessible to TMS via propagated effects. Thus TMS can provide a portal for accessing and altering neural dynamics in networks that are widely distributed anatomically. Finally, when long-term modulation of network dynamics is induced by trains of repetitive TMS, changes in functional connectivity patterns can be studied in parallel with changes in patient symptoms. These correlational data can elucidate neural mechanisms underlying illness and recovery. In this review, we focus on the application of these approaches to the study of psychiatric and neurological illnesses.

  15. Transcranial magnetic stimulation and connectivity mapping: tools for studying the neural bases of brain disorders.

    Directory of Open Access Journals (Sweden)

    Michelle Hampson

    2010-08-01

    Full Text Available There has been an increasing emphasis on characterizing pathophysiology underlying psychiatric and neurological disorders in terms of altered neural connectivity and network dynamics. Transcranial magnetic stimulation (TMS provides a unique opportunity for investigating connectivity in the human brain. TMS allows researchers and clinicians to directly stimulate cortical regions accessible to electromagnetic coils positioned on the scalp. The induced activation can then propagate through long-range connections to other brain areas. Thus, by identifying distal regions activated during TMS, researchers can infer connectivity patterns in the healthy human brain and can examine how those patterns may be disrupted in patients with different brain disorders. Conversely, connectivity maps derived using neuroimaging methods can identify components of a dysfunctional network. Nodes in this dysfunctional network accessible as targets for TMS by virtue of their proximity to the scalp may then permit TMS-induced alterations of components of the network not directly accessible to TMS via propagated effects. Thus TMS can provide a portal for accessing and altering neural dynamics in networks that are widely distributed anatomically. Finally, when long-term modulation of network dynamics is induced by trains of repetitive TMS, changes in functional connectivity patterns can be studied in parallel with changes in patient symptoms. These correlational data can elucidate neural mechanisms underlying illness and recovery. In this review, we focus on the application of these approaches to the study of psychiatric and neurological illnesses.

  16. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

  17. Imaging Posture Veils Neural Signals

    Directory of Open Access Journals (Sweden)

    Robert T Thibault

    2016-10-01

    Full Text Available Whereas modern brain imaging often demands holding body positions incongruent with everyday life, posture governs both neural activity and cognitive performance. Humans commonly perform while upright; yet, many neuroimaging methodologies require participants to remain motionless and adhere to non-ecological comportments within a confined space. This inconsistency between ecological postures and imaging constraints undermines the transferability and generalizability of many a neuroimaging assay.Here we highlight the influence of posture on brain function and behavior. Specifically, we challenge the tacit assumption that brain processes and cognitive performance are comparable across a spectrum of positions. We provide an integrative synthesis regarding the increasingly prominent influence of imaging postures on autonomic function, mental capacity, sensory thresholds, and neural activity. Arguing that neuroimagers and cognitive scientists could benefit from considering the influence posture wields on both general functioning and brain activity, we examine existing imaging technologies and the potential of portable and versatile imaging devices (e.g., functional near infrared spectroscopy. Finally, we discuss ways that accounting for posture may help unveil the complex brain processes of everyday cognition.

  18. Comparative Analysis Between Flaviviruses Reveals Specific Neural Stem Cell Tropism for Zika Virus in the Mouse Developing Neocortex

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Brault

    2016-08-01

    Full Text Available The recent Zika outbreak in South America and French Polynesia was associated with an epidemic of microcephaly, a disease characterized by a reduced size of the cerebral cortex. Other members of the Flavivirus genus, including West Nile virus (WNV, can cause encephalitis but were not demonstrated to cause microcephaly. It remains unclear whether Zika virus (ZIKV and other flaviviruses may infect different cell populations in the developing neocortex and lead to distinct developmental defects. Here, we describe an assay to infect mouse E15 embryonic brain slices with ZIKV, WNV and dengue virus serotype 4 (DENV-4. We show that this tissue is able to support viral replication of ZIKV and WNV, but not DENV-4. Cell fate analysis reveals a remarkable tropism of ZIKV infection for neural stem cells. Closely related WNV displays a very different tropism of infection, with a bias towards neurons. We further show that ZIKV infection, but not WNV infection, impairs cell cycle progression of neural stem cells. Both viruses inhibited apoptosis at early stages of infection. This work establishes a powerful comparative approach to identify ZIKV-specific alterations in the developing neocortex and reveals specific preferential infection of neural stem cells by ZIKV.

  19. An optimal power-dispatching system using neural networks for the electrochemical process of zinc depending on varying prices of electricity.

    Science.gov (United States)

    Yang, Chunhua; Deconinck, G; Gui, Weihua; Li, Yonggang

    2002-01-01

    Depending on varying prices of electricity, an optimal power-dispatching system (OPDS) is developed to minimize the cost of power consumption in the electrochemical process of zinc (EPZ). Due to the complexity of the EPZ, the main factors influencing the power consumption are determined by qualitative analysis, and a series of conditional experiments is conducted to acquire sufficient data, then two backpropagation neural networks are used to describe these relationships quantitatively. An equivalent Hopfield neural network is constructed to solve the optimization problem where a penalty function is introduced into the network energy function so as to meet the equality constraints, and inequality constraints are removed by alteration of the Sigmoid function. This OPDS was put into service in a smeltery in 1998. The cost of power consumption has decreased significantly, the total electrical energy consumption is reduced, and it is also beneficial to balancing the load of the power grid. The actual results show the effectiveness of the OPDS. This paper introduces a successful industrial application and mainly presents how to utilize neural networks to solve particular problems for the real world.

  20. Artificial neural network detects human uncertainty

    Science.gov (United States)

    Hramov, Alexander E.; Frolov, Nikita S.; Maksimenko, Vladimir A.; Makarov, Vladimir V.; Koronovskii, Alexey A.; Garcia-Prieto, Juan; Antón-Toro, Luis Fernando; Maestú, Fernando; Pisarchik, Alexander N.

    2018-03-01

    Artificial neural networks (ANNs) are known to be a powerful tool for data analysis. They are used in social science, robotics, and neurophysiology for solving tasks of classification, forecasting, pattern recognition, etc. In neuroscience, ANNs allow the recognition of specific forms of brain activity from multichannel EEG or MEG data. This makes the ANN an efficient computational core for brain-machine systems. However, despite significant achievements of artificial intelligence in recognition and classification of well-reproducible patterns of neural activity, the use of ANNs for recognition and classification of patterns in neural networks still requires additional attention, especially in ambiguous situations. According to this, in this research, we demonstrate the efficiency of application of the ANN for classification of human MEG trials corresponding to the perception of bistable visual stimuli with different degrees of ambiguity. We show that along with classification of brain states associated with multistable image interpretations, in the case of significant ambiguity, the ANN can detect an uncertain state when the observer doubts about the image interpretation. With the obtained results, we describe the possible application of ANNs for detection of bistable brain activity associated with difficulties in the decision-making process.

  1. Selective estrogen receptor modulators as brain therapeutic agents

    OpenAIRE

    Arévalo, María Ángeles; Santos-Galindo, María; Lagunas, Natalia; Azcoitia, I.; García-Segura, Luis M.

    2011-01-01

    Selective estrogen receptor modulators (SERMs), used for the treatment of breast cancer, osteoporosis, and menopausal symptoms, affect the nervous system. Some SERMs trigger neuroprotective mechanisms and reduce neural damage in different experimental models of neural trauma, brain inflammation, neurodegenerative diseases, cognitive impairment, and affective disorders. New SERMs with specific actions on neurons and glial cells may represent promising therapeutic tools for the brain. © 2011 So...

  2. The Laplacian spectrum of neural networks

    Science.gov (United States)

    de Lange, Siemon C.; de Reus, Marcel A.; van den Heuvel, Martijn P.

    2014-01-01

    The brain is a complex network of neural interactions, both at the microscopic and macroscopic level. Graph theory is well suited to examine the global network architecture of these neural networks. Many popular graph metrics, however, encode average properties of individual network elements. Complementing these “conventional” graph metrics, the eigenvalue spectrum of the normalized Laplacian describes a network's structure directly at a systems level, without referring to individual nodes or connections. In this paper, the Laplacian spectra of the macroscopic anatomical neuronal networks of the macaque and cat, and the microscopic network of the Caenorhabditis elegans were examined. Consistent with conventional graph metrics, analysis of the Laplacian spectra revealed an integrative community structure in neural brain networks. Extending previous findings of overlap of network attributes across species, similarity of the Laplacian spectra across the cat, macaque and C. elegans neural networks suggests a certain level of consistency in the overall architecture of the anatomical neural networks of these species. Our results further suggest a specific network class for neural networks, distinct from conceptual small-world and scale-free models as well as several empirical networks. PMID:24454286

  3. Closed-loop brain training: the science of neurofeedback.

    Science.gov (United States)

    Sitaram, Ranganatha; Ros, Tomas; Stoeckel, Luke; Haller, Sven; Scharnowski, Frank; Lewis-Peacock, Jarrod; Weiskopf, Nikolaus; Blefari, Maria Laura; Rana, Mohit; Oblak, Ethan; Birbaumer, Niels; Sulzer, James

    2017-02-01

    Neurofeedback is a psychophysiological procedure in which online feedback of neural activation is provided to the participant for the purpose of self-regulation. Learning control over specific neural substrates has been shown to change specific behaviours. As a progenitor of brain-machine interfaces, neurofeedback has provided a novel way to investigate brain function and neuroplasticity. In this Review, we examine the mechanisms underlying neurofeedback, which have started to be uncovered. We also discuss how neurofeedback is being used in novel experimental and clinical paradigms from a multidisciplinary perspective, encompassing neuroscientific, neuroengineering and learning-science viewpoints.

  4. Neural decoding of visual imagery during sleep.

    Science.gov (United States)

    Horikawa, T; Tamaki, M; Miyawaki, Y; Kamitani, Y

    2013-05-03

    Visual imagery during sleep has long been a topic of persistent speculation, but its private nature has hampered objective analysis. Here we present a neural decoding approach in which machine-learning models predict the contents of visual imagery during the sleep-onset period, given measured brain activity, by discovering links between human functional magnetic resonance imaging patterns and verbal reports with the assistance of lexical and image databases. Decoding models trained on stimulus-induced brain activity in visual cortical areas showed accurate classification, detection, and identification of contents. Our findings demonstrate that specific visual experience during sleep is represented by brain activity patterns shared by stimulus perception, providing a means to uncover subjective contents of dreaming using objective neural measurement.

  5. Impact of Single or Repeated Dose Intranasal Zinc-free Insulin in Young and Aged F344 Rats on Cognition, Signaling, and Brain Metabolism.

    Science.gov (United States)

    Anderson, Katie L; Frazier, Hilaree N; Maimaiti, Shaniya; Bakshi, Vikas V; Majeed, Zana R; Brewer, Lawrence D; Porter, Nada M; Lin, Ai-Ling; Thibault, Olivier

    2017-02-01

    Novel therapies have turned to delivering compounds to the brain using nasal sprays, bypassing the blood brain barrier, and enriching treatment options for brain aging and/or Alzheimer's disease. We conducted a series of in vivo experiments to test the impact of intranasal Apidra, a zinc-free insulin formulation, on the brain of young and aged F344 rats. Both single acute and repeated daily doses were compared to test the hypothesis that insulin could improve memory recall in aged memory-deficient animals. We quantified insulin signaling in different brain regions and at different times following delivery. We measured cerebral blood flow (CBF) using MRI and also characterized several brain metabolite levels using MR spectroscopy. We show that neither acute nor chronic Apidra improved memory or recall in young or aged animals. Within 2 hours of a single dose, increased insulin signaling was seen in ventral areas of the aged brains only. Although chronic Apidra was able to offset reduced CBF with aging, it also caused significant reductions in markers of neuronal integrity. Our data suggest that this zinc-free insulin formulation may actually hasten cognitive decline with age when used chronically. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Branding and a child's brain: an fMRI study of neural responses to logos.

    Science.gov (United States)

    Bruce, Amanda S; Bruce, Jared M; Black, William R; Lepping, Rebecca J; Henry, Janice M; Cherry, Joseph Bradley C; Martin, Laura E; Papa, Vlad B; Davis, Ann M; Brooks, William M; Savage, Cary R

    2014-01-01

    Branding and advertising have a powerful effect on both familiarity and preference for products, yet no neuroimaging studies have examined neural response to logos in children. Food advertising is particularly pervasive and effective in manipulating choices in children. The purpose of this study was to examine how healthy children's brains respond to common food and other logos. A pilot validation study was first conducted with 32 children to select the most culturally familiar logos, and to match food and non-food logos on valence and intensity. A new sample of 17 healthy weight children were then scanned using functional magnetic resonance imaging. Food logos compared to baseline were associated with increased activation in orbitofrontal cortex and inferior prefrontal cortex. Compared to non-food logos, food logos elicited increased activation in posterior cingulate cortex. Results confirmed that food logos activate some brain regions in children known to be associated with motivation. This marks the first study in children to examine brain responses to culturally familiar logos. Considering the pervasiveness of advertising, research should further investigate how children respond at the neural level to marketing.

  7. Motor sequence learning-induced neural efficiency in functional brain connectivity.

    Science.gov (United States)

    Karim, Helmet T; Huppert, Theodore J; Erickson, Kirk I; Wollam, Mariegold E; Sparto, Patrick J; Sejdić, Ervin; VanSwearingen, Jessie M

    2017-02-15

    Previous studies have shown the functional neural circuitry differences before and after an explicitly learned motor sequence task, but have not assessed these changes during the process of motor skill learning. Functional magnetic resonance imaging activity was measured while participants (n=13) were asked to tap their fingers to visually presented sequences in blocks that were either the same sequence repeated (learning block) or random sequences (control block). Motor learning was associated with a decrease in brain activity during learning compared to control. Lower brain activation was noted in the posterior parietal association area and bilateral thalamus during the later periods of learning (not during the control). Compared to the control condition, we found the task-related motor learning was associated with decreased connectivity between the putamen and left inferior frontal gyrus and left middle cingulate brain regions. Motor learning was associated with changes in network activity, spatial extent, and connectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Neural representation of expected value in the adolescent brain.

    Science.gov (United States)

    Barkley-Levenson, Emily; Galván, Adriana

    2014-01-28

    Previous work shows that the adolescent reward system is hyperactive, but this finding may be confounded by differences in how teens value money. To address this, we examined the neural ontogeny of objective value representation. Adolescent and adult participants performed a monetary gambling task in which they chose to accept or reject gambles of varying expected value. Increasing expected value had a stronger influence over gambling choices in adolescents relative to adults, an effect that was paralleled by greater activation in the ventral striatum in adolescents. This unique adolescent ventral striatum response remained even after matching groups on acceptance behavior. These behavioral and neural data suggest that the value of available options has a greater influence in adolescent versus adult choices, even when objective value and subjective choice are held constant. This research provides further evidence that hyperactivation of reward circuitry in adolescence may be a normative ontogenetic shift that is due to greater valuation in the adolescent brain.

  9. Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches

    Science.gov (United States)

    Ma, Ying; Shaik, Mohammed A.; Kozberg, Mariel G.; Thibodeaux, David N.; Zhao, Hanzhi T.; Yu, Hang

    2016-01-01

    Although modern techniques such as two-photon microscopy can now provide cellular-level three-dimensional imaging of the intact living brain, the speed and fields of view of these techniques remain limited. Conversely, two-dimensional wide-field optical mapping (WFOM), a simpler technique that uses a camera to observe large areas of the exposed cortex under visible light, can detect changes in both neural activity and haemodynamics at very high speeds. Although WFOM may not provide single-neuron or capillary-level resolution, it is an attractive and accessible approach to imaging large areas of the brain in awake, behaving mammals at speeds fast enough to observe widespread neural firing events, as well as their dynamic coupling to haemodynamics. Although such wide-field optical imaging techniques have a long history, the advent of genetically encoded fluorophores that can report neural activity with high sensitivity, as well as modern technologies such as light emitting diodes and sensitive and high-speed digital cameras have driven renewed interest in WFOM. To facilitate the wider adoption and standardization of WFOM approaches for neuroscience and neurovascular coupling research, we provide here an overview of the basic principles of WFOM, considerations for implementation of wide-field fluorescence imaging of neural activity, spectroscopic analysis and interpretation of results. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’. PMID:27574312

  10. Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches.

    Science.gov (United States)

    Ma, Ying; Shaik, Mohammed A; Kim, Sharon H; Kozberg, Mariel G; Thibodeaux, David N; Zhao, Hanzhi T; Yu, Hang; Hillman, Elizabeth M C

    2016-10-05

    Although modern techniques such as two-photon microscopy can now provide cellular-level three-dimensional imaging of the intact living brain, the speed and fields of view of these techniques remain limited. Conversely, two-dimensional wide-field optical mapping (WFOM), a simpler technique that uses a camera to observe large areas of the exposed cortex under visible light, can detect changes in both neural activity and haemodynamics at very high speeds. Although WFOM may not provide single-neuron or capillary-level resolution, it is an attractive and accessible approach to imaging large areas of the brain in awake, behaving mammals at speeds fast enough to observe widespread neural firing events, as well as their dynamic coupling to haemodynamics. Although such wide-field optical imaging techniques have a long history, the advent of genetically encoded fluorophores that can report neural activity with high sensitivity, as well as modern technologies such as light emitting diodes and sensitive and high-speed digital cameras have driven renewed interest in WFOM. To facilitate the wider adoption and standardization of WFOM approaches for neuroscience and neurovascular coupling research, we provide here an overview of the basic principles of WFOM, considerations for implementation of wide-field fluorescence imaging of neural activity, spectroscopic analysis and interpretation of results.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Authors.

  11. Discrete Neural Signatures of Basic Emotions.

    Science.gov (United States)

    Saarimäki, Heini; Gotsopoulos, Athanasios; Jääskeläinen, Iiro P; Lampinen, Jouko; Vuilleumier, Patrik; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri

    2016-06-01

    Categorical models of emotions posit neurally and physiologically distinct human basic emotions. We tested this assumption by using multivariate pattern analysis (MVPA) to classify brain activity patterns of 6 basic emotions (disgust, fear, happiness, sadness, anger, and surprise) in 3 experiments. Emotions were induced with short movies or mental imagery during functional magnetic resonance imaging. MVPA accurately classified emotions induced by both methods, and the classification generalized from one induction condition to another and across individuals. Brain regions contributing most to the classification accuracy included medial and inferior lateral prefrontal cortices, frontal pole, precentral and postcentral gyri, precuneus, and posterior cingulate cortex. Thus, specific neural signatures across these regions hold representations of different emotional states in multimodal fashion, independently of how the emotions are induced. Similarity of subjective experiences between emotions was associated with similarity of neural patterns for the same emotions, suggesting a direct link between activity in these brain regions and the subjective emotional experience. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. DUF581 is plant specific FCS-like zinc finger involved in protein-protein interaction.

    Directory of Open Access Journals (Sweden)

    Muhammed Jamsheer K

    Full Text Available Zinc fingers are a ubiquitous class of protein domain with considerable variation in structure and function. Zf-FCS is a highly diverged group of C2-C2 zinc finger which is present in animals, prokaryotes and viruses, but not in plants. In this study we identified that a plant specific domain of unknown function, DUF581 is a zf-FCS type zinc finger. Based on HMM-HMM comparison and signature motif similarity we named this domain as FCS-Like Zinc finger (FLZ domain. A genome wide survey identified that FLZ domain containing genes are bryophytic in origin and this gene family is expanded in spermatophytes. Expression analysis of selected FLZ gene family members of A. thaliana identified an overlapping expression pattern suggesting a possible redundancy in their function. Unlike the zf-FCS domain, the FLZ domain found to be highly conserved in sequence and structure. Using a combination of bioinformatic and protein-protein interaction tools, we identified that FLZ domain is involved in protein-protein interaction.

  13. The dynamic brain: from spiking neurons to neural masses and cortical fields.

    Directory of Open Access Journals (Sweden)

    Gustavo Deco

    2008-08-01

    Full Text Available The cortex is a complex system, characterized by its dynamics and architecture, which underlie many functions such as action, perception, learning, language, and cognition. Its structural architecture has been studied for more than a hundred years; however, its dynamics have been addressed much less thoroughly. In this paper, we review and integrate, in a unifying framework, a variety of computational approaches that have been used to characterize the dynamics of the cortex, as evidenced at different levels of measurement. Computational models at different space-time scales help us understand the fundamental mechanisms that underpin neural processes and relate these processes to neuroscience data. Modeling at the single neuron level is necessary because this is the level at which information is exchanged between the computing elements of the brain; the neurons. Mesoscopic models tell us how neural elements interact to yield emergent behavior at the level of microcolumns and cortical columns. Macroscopic models can inform us about whole brain dynamics and interactions between large-scale neural systems such as cortical regions, the thalamus, and brain stem. Each level of description relates uniquely to neuroscience data, from single-unit recordings, through local field potentials to functional magnetic resonance imaging (fMRI, electroencephalogram (EEG, and magnetoencephalogram (MEG. Models of the cortex can establish which types of large-scale neuronal networks can perform computations and characterize their emergent properties. Mean-field and related formulations of dynamics also play an essential and complementary role as forward models that can be inverted given empirical data. This makes dynamic models critical in integrating theory and experiments. We argue that elaborating principled and informed models is a prerequisite for grounding empirical neuroscience in a cogent theoretical framework, commensurate with the achievements in the

  14. Parallel neural pathways in higher visual centers of the Drosophila brain that mediate wavelength-specific behavior

    Directory of Open Access Journals (Sweden)

    Hideo eOtsuna

    2014-02-01

    Full Text Available Compared with connections between the retinae and primary visual centers, relatively less is known in both mammals and insects about the functional segregation of neural pathways connecting primary and higher centers of the visual processing cascade. Here, using the Drosophila visual system as a model, we demonstrate two levels of parallel computation in the pathways that connect primary visual centers of the optic lobe to computational circuits embedded within deeper centers in the central brain. We show that a seemingly simple achromatic behavior, namely phototaxis, is under the control of several independent pathways, each of which is responsible for navigation towards unique wavelengths. Silencing just one pathway is enough to disturb phototaxis towards one characteristic monochromatic source, whereas phototactic behavior towards white light is not affected. The response spectrum of each demonstrable pathway is different from that of individual photoreceptors, suggesting subtractive computations. A choice assay between two colors showed that these pathways are responsible for navigation towards, but not for the detection itself of, the monochromatic light. The present study provides novel insights about how visual information is separated and processed in parallel to achieve robust control of an innate behavior.

  15. Classification of brain compartments and head injury lesions by neural networks applied to MRI

    International Nuclear Information System (INIS)

    Kischell, E.R.; Kehtarnavaz, N.; Hillman, G.R.; Levin, H.; Lilly, M.; Kent, T.A.

    1995-01-01

    An automatic, neural network-based approach was applied to segment normal brain compartments and lesions on MR images. Two supervised networks, backpropagation (BPN) and counterpropagation, and two unsupervised networks, Kohonen learning vector quantizer and analog adaptive resonance theory, were trained on registered T2-weighted and proton density images. The classes of interest were background, gray matter, white matter, cerebrospinal fluid, macrocystic encephalomalacia, gliosis, and 'unknown'. A comprehensive feature vector was chosen to discriminate these classes. The BPN combined with feature conditioning, multiple discriminant analysis followed by Hotelling transform, produced the most accurate and consistent classification results. Classifications of normal brain compartments were generally in agreement with expert interpretation of the images. Macrocystic encephalomalacia and gliosis were recognized and, except around the periphery, classified in agreement with the clinician's report used to train the neural network. (orig.)

  16. Classification of brain compartments and head injury lesions by neural networks applied to MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kischell, E R [Dept. of Electrical Engineering, Texas A and M Univ., College Station, TX (United States); Kehtarnavaz, N [Dept. of Electrical Engineering, Texas A and M Univ., College Station, TX (United States); Hillman, G R [Dept. of Pharmacology, Univ. of Texas Medical Branch, Galveston, TX (United States); Levin, H [Dept. of Neurosurgery, Univ. of Texas Medical Branch, Galveston, TX (United States); Lilly, M [Dept. of Neurosurgery, Univ. of Texas Medical Branch, Galveston, TX (United States); Kent, T A [Dept. of Neurology and Psychiatry, Univ. of Texas Medical Branch, Galveston, TX (United States)

    1995-10-01

    An automatic, neural network-based approach was applied to segment normal brain compartments and lesions on MR images. Two supervised networks, backpropagation (BPN) and counterpropagation, and two unsupervised networks, Kohonen learning vector quantizer and analog adaptive resonance theory, were trained on registered T2-weighted and proton density images. The classes of interest were background, gray matter, white matter, cerebrospinal fluid, macrocystic encephalomalacia, gliosis, and `unknown`. A comprehensive feature vector was chosen to discriminate these classes. The BPN combined with feature conditioning, multiple discriminant analysis followed by Hotelling transform, produced the most accurate and consistent classification results. Classifications of normal brain compartments were generally in agreement with expert interpretation of the images. Macrocystic encephalomalacia and gliosis were recognized and, except around the periphery, classified in agreement with the clinician`s report used to train the neural network. (orig.)

  17. Serum zinc, senile plaques, and neurofibrillary tangles: findings from the Nun Study.

    Science.gov (United States)

    Tully, C L; Snowdon, D A; Markesbery, W R

    1995-11-13

    Zinc appears to have a role in binding amyloid precursor protein in vitro, but it is not known whether zinc plays a role in senile plaque formation in vivo in humans. Serum zinc concentrations were available from 12 sisters who died in the Nun Study, a longitudinal study of aging and Alzheimer's disease. Fasting serum zinc concentrations, determined approximately 1 year before death, showed moderate to strong negative correlations with senile plaque counts in seven brain regions. In all brain regions combined, the age-adjusted negative correlations with serum zinc were statistically significant for total senile plaques and diffuse plaques, and suggestive for neuritic plaques. Thus serum zinc in the normal range may be associated with low senile plaque counts in the elderly.

  18. Decoding the neural signatures of emotions expressed through sound.

    Science.gov (United States)

    Sachs, Matthew E; Habibi, Assal; Damasio, Antonio; Kaplan, Jonas T

    2018-03-01

    Effective social functioning relies in part on the ability to identify emotions from auditory stimuli and respond appropriately. Previous studies have uncovered brain regions engaged by the affective information conveyed by sound. But some of the acoustical properties of sounds that express certain emotions vary remarkably with the instrument used to produce them, for example the human voice or a violin. Do these brain regions respond in the same way to different emotions regardless of the sound source? To address this question, we had participants (N = 38, 20 females) listen to brief audio excerpts produced by the violin, clarinet, and human voice, each conveying one of three target emotions-happiness, sadness, and fear-while brain activity was measured with fMRI. We used multivoxel pattern analysis to test whether emotion-specific neural responses to the voice could predict emotion-specific neural responses to musical instruments and vice-versa. A whole-brain searchlight analysis revealed that patterns of activity within the primary and secondary auditory cortex, posterior insula, and parietal operculum were predictive of the affective content of sound both within and across instruments. Furthermore, classification accuracy within the anterior insula was correlated with behavioral measures of empathy. The findings suggest that these brain regions carry emotion-specific patterns that generalize across sounds with different acoustical properties. Also, individuals with greater empathic ability have more distinct neural patterns related to perceiving emotions. These results extend previous knowledge regarding how the human brain extracts emotional meaning from auditory stimuli and enables us to understand and connect with others effectively. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Fishy Business: Effect of Omega-3 Fatty Acids on Zinc Transporters and Free Zinc Availability in Human Neuronal Cells

    Directory of Open Access Journals (Sweden)

    Damitha De Mel

    2014-08-01

    Full Text Available Omega-3 (ω-3 fatty acids are one of the two main families of long chain polyunsaturated fatty acids (PUFA. The main omega-3 fatty acids in the mammalian body are α-linolenic acid (ALA, docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA. Central nervous tissues of vertebrates are characterized by a high concentration of omega-3 fatty acids. Moreover, in the human brain, DHA is considered as the main structural omega-3 fatty acid, which comprises about 40% of the PUFAs in total. DHA deficiency may be the cause of many disorders such as depression, inability to concentrate, excessive mood swings, anxiety, cardiovascular disease, type 2 diabetes, dry skin and so on. On the other hand, zinc is the most abundant trace metal in the human brain. There are many scientific studies linking zinc, especially excess amounts of free zinc, to cellular death. Neurodegenerative diseases, such as Alzheimer’s disease, are characterized by altered zinc metabolism. Both animal model studies and human cell culture studies have shown a possible link between omega-3 fatty acids, zinc transporter levels and free zinc availability at cellular levels. Many other studies have also suggested a possible omega-3 and zinc effect on neurodegeneration and cellular death. Therefore, in this review, we will examine the effect of omega-3 fatty acids on zinc transporters and the importance of free zinc for human neuronal cells. Moreover, we will evaluate the collective understanding of mechanism(s for the interaction of these elements in neuronal research and their significance for the diagnosis and treatment of neurodegeneration.

  20. Fishy business: effect of omega-3 fatty acids on zinc transporters and free zinc availability in human neuronal cells.

    Science.gov (United States)

    De Mel, Damitha; Suphioglu, Cenk

    2014-08-15

    Omega-3 (ω-3) fatty acids are one of the two main families of long chain polyunsaturated fatty acids (PUFA). The main omega-3 fatty acids in the mammalian body are α-linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Central nervous tissues of vertebrates are characterized by a high concentration of omega-3 fatty acids. Moreover, in the human brain, DHA is considered as the main structural omega-3 fatty acid, which comprises about 40% of the PUFAs in total. DHA deficiency may be the cause of many disorders such as depression, inability to concentrate, excessive mood swings, anxiety, cardiovascular disease, type 2 diabetes, dry skin and so on. On the other hand, zinc is the most abundant trace metal in the human brain. There are many scientific studies linking zinc, especially excess amounts of free zinc, to cellular death. Neurodegenerative diseases, such as Alzheimer's disease, are characterized by altered zinc metabolism. Both animal model studies and human cell culture studies have shown a possible link between omega-3 fatty acids, zinc transporter levels and free zinc availability at cellular levels. Many other studies have also suggested a possible omega-3 and zinc effect on neurodegeneration and cellular death. Therefore, in this review, we will examine the effect of omega-3 fatty acids on zinc transporters and the importance of free zinc for human neuronal cells. Moreover, we will evaluate the collective understanding of mechanism(s) for the interaction of these elements in neuronal research and their significance for the diagnosis and treatment of neurodegeneration.

  1. Zinc injection implementation process at EDF: risk analysis, chemical specifications and operating procedures

    International Nuclear Information System (INIS)

    Tigeras, A.; Stutzmann, A.; Bremnes, O.; Claeys, M.; Ranchoux, G.; Segura, J.C.; Errera, J.; Bonne, S.

    2010-01-01

    's strategy and the different measures adopted by EDF to provide the necessary tools to the French units : zinc injection procedures, risk analysis, chemistry -radiochemistry surveillance programs, and chemical specifications. This work can be useful for other utilities, assisting them in optimizing and/or implementing the zinc injection in the most suitable conditions, which would help to obtain the expected results in the current and the future reactors. (author)

  2. Investigation of the GPR39 zinc receptor following inhibition of monoaminergic neurotransmission and potentialization of glutamatergic neurotransmission

    DEFF Research Database (Denmark)

    Młyniec, Katarzyna; Gaweł, Magdalena; Librowski, Tadeusz

    2015-01-01

    Zinc can regulate neural function in the brain via the GPR39 receptor. In the present study we investigated whether inhibition of serotonin, noradrenaline and dopamine synthesis and potentialization of glutamate, via administration of p-chlorophenylalanine (pCPA), α-methyl-p-tyrosine (αMT) and N......-methyl-d-aspartatic acid (NMDA), respectively, would cause changes in GPR39 levels. Western blot analysis showed GPR39 up-regulation following 3-day administration of αMT and NMDA in the frontal cortex, and GPR39 down-regulation following 10-day administration of pCPA, αMT, and NMDA in the hippocampus of CD-1 mice....... There were no changes in serum zinc levels. Additionally, we investigated tryptophan, tyrosine and glutamate concentrations in the hippocampus and frontal cortex of GPR39 knockout (GPR39 KO) mice. Liquid chromatography-mass spectrometry (LC-MS) showed a significant decrease in tryptophan and tyrosine...

  3. SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

    Science.gov (United States)

    Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

    2013-04-30

    The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

  4. Training the brain: practical applications of neural plasticity from the intersection of cognitive neuroscience, developmental psychology, and prevention science.

    Science.gov (United States)

    Bryck, Richard L; Fisher, Philip A

    2012-01-01

    Prior researchers have shown that the brain has a remarkable ability for adapting to environmental changes. The positive effects of such neural plasticity include enhanced functioning in specific cognitive domains and shifts in cortical representation following naturally occurring cases of sensory deprivation; however, maladaptive changes in brain function and development owing to early developmental adversity and stress have also been well documented. Researchers examining enriched rearing environments in animals have revealed the potential for inducing positive brain plasticity effects and have helped to popularize methods for training the brain to reverse early brain deficits or to boost normal cognitive functioning. In this article, two classes of empirically based methods of brain training in children are reviewed and critiqued: laboratory-based, mental process training paradigms and ecological interventions based upon neurocognitive conceptual models. Given the susceptibility of executive function disruption, special attention is paid to training programs that emphasize executive function enhancement. In addition, a third approach to brain training, aimed at tapping into compensatory processes, is postulated. Study results showing the effectiveness of this strategy in the field of neurorehabilitation and in terms of naturally occurring compensatory processing in human aging lend credence to the potential of this approach. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  5. Preschool externalizing behavior predicts gender-specific variation in adolescent neural structure.

    Directory of Open Access Journals (Sweden)

    Jessica Z K Caldwell

    Full Text Available Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life. Our objective was to examine the relationship of early life externalizing behavior with adolescent brain structure. We report here the first longitudinal study linking externalizing behavior during preschool to brain structure during adolescence. We examined the relationship of preschool externalizing behavior with amygdala, hippocampus, and prefrontal cortex volumes at age 15 years in a community sample of 76 adolescents followed longitudinally since their mothers' pregnancy. A significant gender by externalizing behavior interaction revealed that males-but not females-with greater early childhood externalizing behavior had smaller amygdala volumes at adolescence (t = 2.33, p = .023. No significant results were found for the hippocampus or the prefrontal cortex. Greater early externalizing behavior also related to smaller volume of a cluster including the angular gyrus and tempoparietal junction across genders. Results were not attributable to the impact of preschool anxiety, preschool maternal stress, school-age internalizing or externalizing behaviors, or adolescent substance use. These findings demonstrate a novel, gender-specific relationship between early-childhood externalizing behavior and adolescent amygdala volume, as well as a cross-gender result for the angular gyrus and tempoparietal junction.

  6. Functional specificity in the human brain: A window into the functional architecture of the mind

    Science.gov (United States)

    Kanwisher, Nancy

    2010-01-01

    Is the human mind/brain composed of a set of highly specialized components, each carrying out a specific aspect of human cognition, or is it more of a general-purpose device, in which each component participates in a wide variety of cognitive processes? For nearly two centuries, proponents of specialized organs or modules of the mind and brain—from the phrenologists to Broca to Chomsky and Fodor—have jousted with the proponents of distributed cognitive and neural processing—from Flourens to Lashley to McClelland and Rumelhart. I argue here that research using functional MRI is beginning to answer this long-standing question with new clarity and precision by indicating that at least a few specific aspects of cognition are implemented in brain regions that are highly specialized for that process alone. Cortical regions have been identified that are specialized not only for basic sensory and motor processes but also for the high-level perceptual analysis of faces, places, bodies, visually presented words, and even for the very abstract cognitive function of thinking about another person’s thoughts. I further consider the as-yet unanswered questions of how much of the mind and brain are made up of these functionally specialized components and how they arise developmentally. PMID:20484679

  7. Zinc triggers microglial activation.

    Science.gov (United States)

    Kauppinen, Tiina M; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A

    2008-05-28

    Microglia are resident immune cells of the CNS. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, "ameboid" morphology and release matrix metalloproteinases, reactive oxygen species, and other proinflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here, we show that zinc directly triggers microglial activation. Microglia transfected with a nuclear factor-kappaB (NF-kappaB) reporter gene showed a severalfold increase in NF-kappaB activity in response to 30 microm zinc. Cultured mouse microglia exposed to 15-30 microm zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-kappaB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-kappaB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders.

  8. Feasibility and resolution limits of opto-magnetic imaging of neural network activity in brain slices using color centers in diamond

    DEFF Research Database (Denmark)

    Karadas, Mürsel; Wojciechowski, Adam M.; Huck, Alexander

    2018-01-01

    We suggest a novel approach for wide-field imaging of the neural network dynamics of brain slices that uses highly sensitivity magnetometry based on nitrogen-vacancy (NV) centers in diamond. Invitro recordings in brain slices is a proven method for the characterization of electrical neural activi...... cell. Our results suggest that imaging of slice activity will be possible with the upcoming generation of NV magnetic field sensors, while single-shot imaging of planar cell activity remains challenging....

  9. Detection of neural activity in the brains of Japanese honeybee workers during the formation of a "hot defensive bee ball".

    Directory of Open Access Journals (Sweden)

    Atsushi Ugajin

    Full Text Available Anti-predator behaviors are essential to survival for most animals. The neural bases of such behaviors, however, remain largely unknown. Although honeybees commonly use their stingers to counterattack predators, the Japanese honeybee (Apis cerana japonica uses a different strategy to fight against the giant hornet (Vespa mandarinia japonica. Instead of stinging the hornet, Japanese honeybees form a "hot defensive bee ball" by surrounding the hornet en masse, killing it with heat. The European honeybee (A. mellifera ligustica, on the other hand, does not exhibit this behavior, and their colonies are often destroyed by a hornet attack. In the present study, we attempted to analyze the neural basis of this behavior by mapping the active brain regions of Japanese honeybee workers during the formation of a hot defensive bee ball. First, we identified an A. cerana homolog (Acks = Apis cerana kakusei of kakusei, an immediate early gene that we previously identified from A. mellifera, and showed that Acks has characteristics similar to kakusei and can be used to visualize active brain regions in A. cerana. Using Acks as a neural activity marker, we demonstrated that neural activity in the mushroom bodies, especially in Class II Kenyon cells, one subtype of mushroom body intrinsic neurons, and a restricted area between the dorsal lobes and the optic lobes was increased in the brains of Japanese honeybee workers involved in the formation of a hot defensive bee ball. In addition, workers exposed to 46°C heat also exhibited Acks expression patterns similar to those observed in the brains of workers involved in the formation of a hot defensive bee ball, suggesting that the neural activity observed in the brains of workers involved in the hot defensive bee ball mainly reflects thermal stimuli processing.

  10. Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain.

    Science.gov (United States)

    Chang, Mengqi; Lv, Hongyi; Zhang, Weilong; Ma, Chunhui; He, Xue; Zhao, Shunli; Zhang, Zhi-Wei; Zeng, Yi-Xin; Song, Shuhui; Niu, Yamei; Tong, Wei-Min

    2017-09-01

    N 6 -methyladenosine (m 6 A) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high m 6 A levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile. RNA methylation levels in mouse cerebellum are generally higher than those in the cerebral cortex. Heterogeneity of RNA methylation exists across different brain regions and different types of neural cells including the mRNAs to be methylated, their methylation levels and methylation site selection. Common and region-specific methylation have different preferences for methylation site selection and thereby different impacts on their biological functions. In addition, high methylation levels of fragile X mental retardation protein (FMRP) target mRNAs suggest that m 6 A methylation is likely to be used for selective recognition of target mRNAs by FMRP in the synapse. Overall, we provide a region-specific map of RNA m 6 A methylation and characterize the distinct features of specific and common methylation in mouse cerebellum and cerebral cortex. Our results imply that RNA m 6 A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain. © 2017 The Authors.

  11. Essential role for zinc-triggered p75NTR activation in preconditioning neuroprotection.

    Science.gov (United States)

    Lee, Jin-Yeon; Kim, Yu-Jin; Kim, Tae-Youn; Koh, Jae-Young; Kim, Yang-Hee

    2008-10-22

    Ischemic preconditioning (PC) of the brain is a phenomenon by which mild ischemic insults render neurons resistant to subsequent strong insults. Key steps in ischemic PC of the brain include caspase-3 activation and poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, but upstream events have not been clearly elucidated. We have tested whether endogenous zinc is required for ischemic PC of the brain in rats. Mild, transient zinc accumulation was observed in certain neurons after ischemic PC. Moreover, intraventricular administration of CaEDTA during ischemic PC abrogated both zinc accumulation and the protective effect against subsequent full ischemia. To elucidate the mechanism of the zinc-triggered PC (Zn PC) effect, cortical cultures were exposed to sublethal levels of zinc, and 18 h later to lethal levels of zinc or NMDA. Zn PC exhibited the characteristic features of ischemic PC, including caspase-3 activation, PARP-1 cleavage, and HSP70 induction, all of which are crucial for subsequent neuroprotection against NMDA or zinc toxicity. HSP70 induction was necessary for protection, as it halted caspase-3 activation before apoptosis. Interestingly, in both Zn PC in vitro and ischemic PC in vivo, p75(NTR) was necessary for neuroprotection. These results suggest that caspase-3 activation during ischemic PC, a necessary event for subsequent neuroprotection, may result from mild zinc accumulation and the consequent p75(NTR) activation in neurons.

  12. Automatic brain MR image denoising based on texture feature-based artificial neural networks.

    Science.gov (United States)

    Chang, Yu-Ning; Chang, Herng-Hua

    2015-01-01

    Noise is one of the main sources of quality deterioration not only for visual inspection but also in computerized processing in brain magnetic resonance (MR) image analysis such as tissue classification, segmentation and registration. Accordingly, noise removal in brain MR images is important for a wide variety of subsequent processing applications. However, most existing denoising algorithms require laborious tuning of parameters that are often sensitive to specific image features and textures. Automation of these parameters through artificial intelligence techniques will be highly beneficial. In the present study, an artificial neural network associated with image texture feature analysis is proposed to establish a predictable parameter model and automate the denoising procedure. In the proposed approach, a total of 83 image attributes were extracted based on four categories: 1) Basic image statistics. 2) Gray-level co-occurrence matrix (GLCM). 3) Gray-level run-length matrix (GLRLM) and 4) Tamura texture features. To obtain the ranking of discrimination in these texture features, a paired-samples t-test was applied to each individual image feature computed in every image. Subsequently, the sequential forward selection (SFS) method was used to select the best texture features according to the ranking of discrimination. The selected optimal features were further incorporated into a back propagation neural network to establish a predictable parameter model. A wide variety of MR images with various scenarios were adopted to evaluate the performance of the proposed framework. Experimental results indicated that this new automation system accurately predicted the bilateral filtering parameters and effectively removed the noise in a number of MR images. Comparing to the manually tuned filtering process, our approach not only produced better denoised results but also saved significant processing time.

  13. Expression and function of orphan nuclear receptor TLX in adult neural stem cells.

    Science.gov (United States)

    Shi, Yanhong; Chichung Lie, D; Taupin, Philippe; Nakashima, Kinichi; Ray, Jasodhara; Yu, Ruth T; Gage, Fred H; Evans, Ronald M

    2004-01-01

    The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

  14. Regulation of Msx genes by a Bmp gradient is essential for neural crest specification.

    Science.gov (United States)

    Tribulo, Celeste; Aybar, Manuel J; Nguyen, Vu H; Mullins, Mary C; Mayor, Roberto

    2003-12-01

    There is evidence in Xenopus and zebrafish embryos that the neural crest/neural folds are specified at the border of the neural plate by a precise threshold concentration of a Bmp gradient. In order to understand the molecular mechanism by which a gradient of Bmp is able to specify the neural crest, we analyzed how the expression of Bmp targets, the Msx genes, is regulated and the role that Msx genes has in neural crest specification. As Msx genes are directly downstream of Bmp, we analyzed Msx gene expression after experimental modification in the level of Bmp activity by grafting a bead soaked with noggin into Xenopus embryos, by expressing in the ectoderm a dominant-negative Bmp4 or Bmp receptor in Xenopus and zebrafish embryos, and also through Bmp pathway component mutants in the zebrafish. All the results show that a reduction in the level of Bmp activity leads to an increase in the expression of Msx genes in the neural plate border. Interestingly, by reaching different levels of Bmp activity in animal cap ectoderm, we show that a specific concentration of Bmp induces msx1 expression to a level similar to that required to induce neural crest. Our results indicate that an intermediate level of Bmp activity specifies the expression of Msx genes in the neural fold region. In addition, we have analyzed the role that msx1 plays on neural crest specification. As msx1 has a role in dorsoventral pattering, we have carried out conditional gain- and loss-of-function experiments using different msx1 constructs fused to a glucocorticoid receptor element to avoid an early effect of this factor. We show that msx1 expression is able to induce all other early neural crest markers tested (snail, slug, foxd3) at the time of neural crest specification. Furthermore, the expression of a dominant negative of Msx genes leads to the inhibition of all the neural crest markers analyzed. It has been previously shown that snail is one of the earliest genes acting in the neural crest

  15. Modification of surface/neuron interfaces for neural cell-type specific responses: a review

    International Nuclear Information System (INIS)

    Chen, Cen; Kong, Xiangdong; Lee, In-Seop

    2016-01-01

    Surface/neuron interfaces have played an important role in neural repair including neural prostheses and tissue engineered scaffolds. This comprehensive literature review covers recent studies on the modification of surface/neuron interfaces. These interfaces are identified in cases both where the surfaces of substrates or scaffolds were in direct contact with cells and where the surfaces were modified to facilitate cell adhesion and controlling cell-type specific responses. Different sources of cells for neural repair are described, such as pheochromocytoma neuronal-like cell, neural stem cell (NSC), embryonic stem cell (ESC), mesenchymal stem cell (MSC) and induced pluripotent stem cell (iPS). Commonly modified methods are discussed including patterned surfaces at micro- or nano-scale, surface modification with conducting coatings, and functionalized surfaces with immobilized bioactive molecules. These approaches to control cell-type specific responses have enormous potential implications in neural repair. (paper)

  16. A Heuristic Approach to Intra-Brain Communications Using Chaos in a Recurrent Neural Network Model

    Science.gov (United States)

    Soma, Ken-ichiro; Mori, Ryota; Sato, Ryuichi; Nara, Shigetoshi

    2011-09-01

    To approach functional roles of chaos in brain, a heuristic model to consider mechanisms of intra-brain communications is proposed. The key idea is to use chaos in firing pattern dynamics of a recurrent neural network consisting of birary state neurons, as propagation medium of pulse signals. Computer experiments and numerical methods are introduced to evaluate signal transport characteristics by calculating correlation functions between sending neurons and receiving neurons of pulse signals.

  17. Brain tissue aspiration neural tube defect Aspiração de tecido cerebral em casos de defeitos de fechamento do tubo neural

    Directory of Open Access Journals (Sweden)

    Luiz Cesar Peres

    2005-09-01

    Full Text Available The study aimed to find out how frequent is brain tissue aspiration and if brain tissue heterotopia could be found in the lung of human neural tube defect cases. Histological sections of each lobe of both lungs of 22 fetuses and newborn with neural tube defect were immunostained for glial fibrillary acidic protein (GFAP. There were 15 (68.2% females and 7 (31.8% males. Age ranged from 18 to 40 weeks of gestation (mean= 31.8. Ten (45.5% were stillborn, the same newborn, and 2 (9.1% were abortuses. Diagnosis were: craniorrhachischisis (9 cases, 40.9%, anencephaly (8 cases, 36,4%, ruptured occipital encephalocele and rachischisis (2 cases, 9.1% each, and early amniotic band disruption sequence (1 case, 4.5%. Only one case (4.5% exhibited GFAP positive cells inside bronchioles and alveoli admixed to epithelial amniotic squames. No heterotopic tissue was observed in the lung interstitium. We concluded that aspiration of brain tissue from the amniotic fluid in neural tube defect cases may happen but it is infrequent and heterotopia was not observed.O objetivo do estudo foi identificar qual a freqüência de aspiração de tecido cerebral e a existência de heterotopia nos pulmões de casos humanos de defeito de fechamento do tubo neural através da reação imuno-histoquímica para proteína fibrilar glial ácida (GFAP em cortes histológicos de todos os lobos de ambos os pulmões de 22 casos de fetos e neonatos com defeito de fechamento do tubo neural. Havia 15 casos femininos (68,2% e 7 masculinos (31,8%, com idade gestacional variando de 18 a 40 semanas (média= 31,8, sendo natimortos e neomortos 10 (45,5% cada e 2 (9,1% abortos. Os diagnósticos foram: Craniorraquisquise (9 casos, 40,9%, anencefalia (8 casos, 36,4%, encefalocele occipital rota e raquisquise (2 casos, 9,1% e 1 (4,5%caso de seqüência de disruptura amniótica precoce. Somente 1 caso (4,5% apresentou células positivas dentro de bronquíolos e alvéolos em meio a células epiteliais

  18. Altered behavior and neural activity in conspecific cagemates co-housed with mouse models of brain disorders.

    Science.gov (United States)

    Yang, Hyunwoo; Jung, Seungmoon; Seo, Jinsoo; Khalid, Arshi; Yoo, Jung-Seok; Park, Jihyun; Kim, Soyun; Moon, Jangsup; Lee, Soon-Tae; Jung, Keun-Hwa; Chu, Kon; Lee, Sang Kun; Jeon, Daejong

    2016-09-01

    The psychosocial environment is one of the major contributors of social stress. Family members or caregivers who consistently communicate with individuals with brain disorders are considered at risk for physical and mental health deterioration, possibly leading to mental disorders. However, the underlying neural mechanisms of this phenomenon remain poorly understood. To address this, we developed a social stress paradigm in which a mouse model of epilepsy or depression was housed long-term (>4weeks) with normal conspecifics. We characterized the behavioral phenotypes and electrophysiologically investigated the neural activity of conspecific cagemate mice. The cagemates exhibited deficits in behavioral tasks assessing anxiety, locomotion, learning/memory, and depression-like behavior. Furthermore, they showed severe social impairment in social behavioral tasks involving social interaction or aggression. Strikingly, behavioral dysfunction remained in the cagemates 4weeks following co-housing cessation with the mouse models. In an electrophysiological study, the cagemates showed an increased number of spikes in medial prefrontal cortex (mPFC) neurons. Our results demonstrate that conspecifics co-housed with mouse models of brain disorders develop chronic behavioral dysfunctions, and suggest a possible association between abnormal mPFC neural activity and their behavioral pathogenesis. These findings contribute to the understanding of the psychosocial and psychiatric symptoms frequently present in families or caregivers of patients with brain disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Neural evidence that human emotions share core affective properties.

    Science.gov (United States)

    Wilson-Mendenhall, Christine D; Barrett, Lisa Feldman; Barsalou, Lawrence W

    2013-06-01

    Research on the "emotional brain" remains centered around the idea that emotions like fear, happiness, and sadness result from specialized and distinct neural circuitry. Accumulating behavioral and physiological evidence suggests, instead, that emotions are grounded in core affect--a person's fluctuating level of pleasant or unpleasant arousal. A neuroimaging study revealed that participants' subjective ratings of valence (i.e., pleasure/displeasure) and of arousal evoked by various fear, happiness, and sadness experiences correlated with neural activity in specific brain regions (orbitofrontal cortex and amygdala, respectively). We observed these correlations across diverse instances within each emotion category, as well as across instances from all three categories. Consistent with a psychological construction approach to emotion, the results suggest that neural circuitry realizes more basic processes across discrete emotions. The implicated brain regions regulate the body to deal with the world, producing the affective changes at the core of emotions and many other psychological phenomena.

  20. A neural population model incorporating dopaminergic neurotransmission during complex voluntary behaviors.

    Directory of Open Access Journals (Sweden)

    Stefan Fürtinger

    2014-11-01

    Full Text Available Assessing brain activity during complex voluntary motor behaviors that require the recruitment of multiple neural sites is a field of active research. Our current knowledge is primarily based on human brain imaging studies that have clear limitations in terms of temporal and spatial resolution. We developed a physiologically informed non-linear multi-compartment stochastic neural model to simulate functional brain activity coupled with neurotransmitter release during complex voluntary behavior, such as speech production. Due to its state-dependent modulation of neural firing, dopaminergic neurotransmission plays a key role in the organization of functional brain circuits controlling speech and language and thus has been incorporated in our neural population model. A rigorous mathematical proof establishing existence and uniqueness of solutions to the proposed model as well as a computationally efficient strategy to numerically approximate these solutions are presented. Simulated brain activity during the resting state and sentence production was analyzed using functional network connectivity, and graph theoretical techniques were employed to highlight differences between the two conditions. We demonstrate that our model successfully reproduces characteristic changes seen in empirical data between the resting state and speech production, and dopaminergic neurotransmission evokes pronounced changes in modeled functional connectivity by acting on the underlying biological stochastic neural model. Specifically, model and data networks in both speech and rest conditions share task-specific network features: both the simulated and empirical functional connectivity networks show an increase in nodal influence and segregation in speech over the resting state. These commonalities confirm that dopamine is a key neuromodulator of the functional connectome of speech control. Based on reproducible characteristic aspects of empirical data, we suggest a number

  1. Patterns of cortical oscillations organize neural activity into whole-brain functional networks evident in the fMRI BOLD signal

    Directory of Open Access Journals (Sweden)

    Jennifer C Whitman

    2013-03-01

    Full Text Available Recent findings from electrophysiology and multimodal neuroimaging have elucidated the relationship between patterns of cortical oscillations evident in EEG / MEG and the functional brain networks evident in the BOLD signal. Much of the existing literature emphasized how high-frequency cortical oscillations are thought to coordinate neural activity locally, while low-frequency oscillations play a role in coordinating activity between more distant brain regions. However, the assignment of different frequencies to different spatial scales is an oversimplification. A more informative approach is to explore the arrangements by which these low- and high-frequency oscillations work in concert, coordinating neural activity into whole-brain functional networks. When relating such networks to the BOLD signal, we must consider how the patterns of cortical oscillations change at the same speed as cognitive states, which often last less than a second. Consequently, the slower BOLD signal may often reflect the summed neural activity of several transient network configurations. This temporal mismatch can be circumvented if we use spatial maps to assess correspondence between oscillatory networks and BOLD networks.

  2. Learning-induced neural plasticity of speech processing before birth.

    Science.gov (United States)

    Partanen, Eino; Kujala, Teija; Näätänen, Risto; Liitola, Auli; Sambeth, Anke; Huotilainen, Minna

    2013-09-10

    Learning, the foundation of adaptive and intelligent behavior, is based on plastic changes in neural assemblies, reflected by the modulation of electric brain responses. In infancy, auditory learning implicates the formation and strengthening of neural long-term memory traces, improving discrimination skills, in particular those forming the prerequisites for speech perception and understanding. Although previous behavioral observations show that newborns react differentially to unfamiliar sounds vs. familiar sound material that they were exposed to as fetuses, the neural basis of fetal learning has not thus far been investigated. Here we demonstrate direct neural correlates of human fetal learning of speech-like auditory stimuli. We presented variants of words to fetuses; unlike infants with no exposure to these stimuli, the exposed fetuses showed enhanced brain activity (mismatch responses) in response to pitch changes for the trained variants after birth. Furthermore, a significant correlation existed between the amount of prenatal exposure and brain activity, with greater activity being associated with a higher amount of prenatal speech exposure. Moreover, the learning effect was generalized to other types of similar speech sounds not included in the training material. Consequently, our results indicate neural commitment specifically tuned to the speech features heard before birth and their memory representations.

  3. Specific binding of atrial natriuretic factor in brain microvessels

    International Nuclear Information System (INIS)

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

    1987-01-01

    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 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 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

  4. Motor-related brain activity during action observation: a neural substrate for electrocorticographic brain-computer interfaces after spinal cord injury

    Directory of Open Access Journals (Sweden)

    Jennifer L Collinger

    2014-02-01

    Full Text Available After spinal cord injury (SCI, motor commands from the brain are unable to reach peripheral nerves and muscles below the level of the lesion. Action observation, in which a person observes someone else performing an action, has been used to augment traditional rehabilitation paradigms. Similarly, action observation can be used to derive the relationship between brain activity and movement kinematics for a motor-based brain-computer interface (BCI even when the user cannot generate overt movements. BCIs use brain signals to control external devices to replace functions that have been lost due to SCI or other motor impairment. Previous studies have reported congruent motor cortical activity during observed and overt movements using magnetoencephalography (MEG and functional magnetic resonance imaging (fMRI. Recent single-unit studies using intracortical microelectrodes also demonstrated that a large number of motor cortical neurons had similar firing rate patterns between overt and observed movements. Given the increasing interest in electrocorticography (ECoG-based BCIs, our goal was to identify whether action observation-related cortical activity could be recorded using ECoG during grasping tasks. Specifically, we aimed to identify congruent neural activity during observed and executed movements in both the sensorimotor rhythm (10-40 Hz and the high-gamma band (65-115 Hz which contains significant movement-related information. We observed significant motor-related high-gamma band activity during action observation in both able-bodied individuals and one participant with a complete C4 SCI. Furthermore, in able-bodied participants, both the low and high frequency bands demonstrated congruent activity between action execution and observation. Our results suggest that action observation could be an effective and critical procedure for deriving the mapping from ECoG signals to intended movement for an ECoG-based BCI system for individuals with

  5. Physics strategies for sparing neural stem cells during whole-brain radiation treatments

    International Nuclear Information System (INIS)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J.

    2011-01-01

    Purpose: Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. Methods: Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. Results: The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. Conclusions: Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

  6. Fear-of-intimacy-mediated zinc transport controls the function of zinc-finger transcription factors involved in myogenesis.

    Science.gov (United States)

    Carrasco-Rando, Marta; Atienza-Manuel, Alexandra; Martín, Paloma; Burke, Richard; Ruiz-Gómez, Mar

    2016-06-01

    Zinc is a component of one-tenth of all human proteins. Its cellular concentration is tightly regulated because its dyshomeostasis has catastrophic health consequences. Two families of zinc transporters control zinc homeostasis in organisms, but there is little information about their specific developmental roles. We show that the ZIP transporter Fear-of-intimacy (Foi) is necessary for the formation of Drosophila muscles. In foi mutants, myoblasts segregate normally, but their specification is affected, leading to the formation of a misshapen muscle pattern and distorted midgut. The observed phenotypes could be ascribed to the inactivation of specific zinc-finger transcription factors (ZFTFs), supporting the hypothesis that they are a consequence of intracellular depletion of zinc. Accordingly, foi phenotypes can be rescued by mesodermal expression of other ZIP members with similar subcellular localization. We propose that Foi acts mostly as a transporter to regulate zinc intracellular homeostasis, thereby impacting on the activity of ZFTFs that control specific developmental processes. Our results additionally suggest a possible explanation for the presence of large numbers of zinc transporters in organisms based on differences in ion transport specificity and/or degrees of activity among transporters. © 2016. Published by The Company of Biologists Ltd.

  7. Brain Dynamics in Predicting Driving Fatigue Using a Recurrent Self-Evolving Fuzzy Neural Network.

    Science.gov (United States)

    Liu, Yu-Ting; Lin, Yang-Yin; Wu, Shang-Lin; Chuang, Chun-Hsiang; Lin, Chin-Teng

    2016-02-01

    This paper proposes a generalized prediction system called a recurrent self-evolving fuzzy neural network (RSEFNN) that employs an on-line gradient descent learning rule to address the electroencephalography (EEG) regression problem in brain dynamics for driving fatigue. The cognitive states of drivers significantly affect driving safety; in particular, fatigue driving, or drowsy driving, endangers both the individual and the public. For this reason, the development of brain-computer interfaces (BCIs) that can identify drowsy driving states is a crucial and urgent topic of study. Many EEG-based BCIs have been developed as artificial auxiliary systems for use in various practical applications because of the benefits of measuring EEG signals. In the literature, the efficacy of EEG-based BCIs in recognition tasks has been limited by low resolutions. The system proposed in this paper represents the first attempt to use the recurrent fuzzy neural network (RFNN) architecture to increase adaptability in realistic EEG applications to overcome this bottleneck. This paper further analyzes brain dynamics in a simulated car driving task in a virtual-reality environment. The proposed RSEFNN model is evaluated using the generalized cross-subject approach, and the results indicate that the RSEFNN is superior to competing models regardless of the use of recurrent or nonrecurrent structures.

  8. Age-and Brain Region-Specific Differences in Mitochondrial ...

    Science.gov (United States)

    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 bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 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 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

  9. Targeting neural endophenotypes of eating disorders with non-invasive brain stimulation

    Directory of Open Access Journals (Sweden)

    Katharine A Dunlop

    2016-02-01

    Full Text Available The term eating disorders (ED encompasses a wide variety of disordered eating and compensatory behaviors, and so the term is associated with considerable clinical and phenotypic heterogeneity. This heterogeneity makes optimizing treatment techniques difficult. One class of treatments is non-invasive brain stimulation (NIBS. NIBS, including repetitive transcranial magnetic stimulation (rTMS and transcranial direct current stimulation (tDCS are accessible forms of neuromodulation that alter the cortical excitability of a target brain region. It is crucial for NIBS to be successful that the target is well selected for the patient population in question. Targets may best be selected by stepping back from conventional DSM-5 diagnostic criteria to identify neural substrates of more basic phenotypes, including behavior related rewards and punishment cognitive control, and social processes. These phenotypic dimensions have been recently laid out by the Research Domain Criteria (RDoC initiative. Consequently, this review is intended to identify potential dimensions as outlined by the RDoC and their underlying behavioral and neurobiological targets associated with ED as potential candidates for NIBS and review the available literature on rTMS and tDCS in ED. This review systematically reviews abnormal neural circuitry in ED within the RDoC framework, and also systematically reviews the available literature investigating NIBS as a treatment for ED.

  10. Decreased N-TAF1 expression in X-linked dystonia-parkinsonism patient-specific neural stem cells

    Directory of Open Access Journals (Sweden)

    Naoto Ito

    2016-04-01

    Full Text Available X-linked dystonia-parkinsonism (XDP is a hereditary neurodegenerative disorder involving a progressive loss of striatal medium spiny neurons. The mechanisms underlying neurodegeneration are not known, in part because there have been few cellular models available for studying the disease. The XDP haplotype consists of multiple sequence variations in a region of the X chromosome containing TAF1, a large gene with at least 38 exons, and a multiple transcript system (MTS composed of five unconventional exons. A previous study identified an XDP-specific insertion of a SINE-VNTR-Alu (SVA-type retrotransposon in intron 32 of TAF1, as well as a neural-specific TAF1 isoform, N-TAF1, which showed decreased expression in post-mortem XDP brain compared with control tissue. Here, we generated XDP patient and control fibroblasts and induced pluripotent stem cells (iPSCs in order to further probe cellular defects associated with this disease. As initial validation of the model, we compared expression of TAF1 and MTS transcripts in XDP versus control fibroblasts and iPSC-derived neural stem cells (NSCs. Compared with control cells, XDP fibroblasts exhibited decreased expression of TAF1 transcript fragments derived from exons 32-36, a region spanning the SVA insertion site. N-TAF1, which incorporates an alternative exon (exon 34′, was not expressed in fibroblasts, but was detectable in iPSC-differentiated NSCs at levels that were ∼threefold lower in XDP cells than in controls. These results support the previous findings that N-TAF1 expression is impaired in XDP, but additionally indicate that this aberrant transcription might occur in neural cells at relatively early stages of development that precede neurodegeneration.

  11. Branding and a child’s brain: an fMRI study of neural responses to logos

    Science.gov (United States)

    Bruce, Jared M.; Black, William R.; Lepping, Rebecca J.; Henry, Janice M.; Cherry, Joseph Bradley C.; Martin, Laura E.; Papa, Vlad B.; Davis, Ann M.; Brooks, William M.; Savage, Cary R.

    2014-01-01

    Branding and advertising have a powerful effect on both familiarity and preference for products, yet no neuroimaging studies have examined neural response to logos in children. Food advertising is particularly pervasive and effective in manipulating choices in children. The purpose of this study was to examine how healthy children’s brains respond to common food and other logos. A pilot validation study was first conducted with 32 children to select the most culturally familiar logos, and to match food and non-food logos on valence and intensity. A new sample of 17 healthy weight children were then scanned using functional magnetic resonance imaging. Food logos compared to baseline were associated with increased activation in orbitofrontal cortex and inferior prefrontal cortex. Compared to non-food logos, food logos elicited increased activation in posterior cingulate cortex. Results confirmed that food logos activate some brain regions in children known to be associated with motivation. This marks the first study in children to examine brain responses to culturally familiar logos. Considering the pervasiveness of advertising, research should further investigate how children respond at the neural level to marketing. PMID:22997054

  12. Brain machine interfaces combining microelectrode arrays with nanostructured optical biochemical sensors

    Science.gov (United States)

    Hajj-Hassan, Mohamad; Gonzalez, Timothy; Ghafer-Zadeh, Ebrahim; Chodavarapu, Vamsy; Musallam, Sam; Andrews, Mark

    2009-02-01

    Neural microelectrodes are an important component of neural prosthetic systems which assist paralyzed patients by allowing them to operate computers or robots using their neural activity. These microelectrodes are also used in clinical settings to localize the locus of seizure initiation in epilepsy or to stimulate sub-cortical structures in patients with Parkinson's disease. In neural prosthetic systems, implanted microelectrodes record the electrical potential generated by specific thoughts and relay the signals to algorithms trained to interpret these thoughts. In this paper, we describe novel elongated multi-site neural electrodes that can record electrical signals and specific neural biomarkers and that can reach depths greater than 8mm in the sulcus of non-human primates (monkeys). We hypothesize that additional signals recorded by the multimodal probes will increase the information yield when compared to standard probes that record just electropotentials. We describe integration of optical biochemical sensors with neural microelectrodes. The sensors are made using sol-gel derived xerogel thin films that encapsulate specific biomarker responsive luminophores in their nanostructured pores. The desired neural biomarkers are O2, pH, K+, and Na+ ions. As a prototype, we demonstrate direct-write patterning to create oxygen-responsive xerogel waveguide structures on the neural microelectrodes. The recording of neural biomarkers along with electrical activity could help the development of intelligent and more userfriendly neural prosthesis/brain machine interfaces as well as aid in providing answers to complex brain diseases and disorders.

  13. Human-like brain hemispheric dominance in birdsong learning.

    Science.gov (United States)

    Moorman, Sanne; Gobes, Sharon M H; Kuijpers, Maaike; Kerkhofs, Amber; Zandbergen, Matthijs A; Bolhuis, Johan J

    2012-07-31

    Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca's area in the frontal lobe and Wernicke's area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke's area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms.

  14. In-Vivo Characterization of Glassy Carbon Micro-Electrode Arrays for Neural Applications and Histological Analysis of the Brain Tissue

    Science.gov (United States)

    Vomero, Maria

    The aim of this work is to fabricate and characterize glassy carbon Microelectrode Arrays (MEAs) for sensing and stimulating neural activity, and conduct histological analysis of the brain tissue after the implant to determine long-term performance. Neural applications often require robust electrical and electrochemical response over a long period of time, and for those applications we propose to replace the commonly used noble metals like platinum, gold and iridium with glassy carbon. We submit that such material has the potential to improve the performances of traditional neural prostheses, thanks to better charge transfer capabilities and higher electrochemical stability. Great interest and attention is given in this work, in particular, to the investigation of tissue response after several weeks of implants in rodents' brain motor cortex and the associated materials degradation. As part of this work, a new set of devices for Electrocorticography (ECoG) has been designed and fabricated to improve durability and quality of the previous generation of devices, designed and manufactured by the same research group in 2014. In-vivo long-term impedance measurements and brain activity recordings were performed to test the functionality of the neural devices. In-vitro electrical characterization of the carbon electrodes, as well as the study of the adhesion mechanisms between glassy carbon and different substrates is also part of the research described in this book.

  15. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders

    NARCIS (Netherlands)

    Kos, Claire; van Tol, Marie-Jose; Marsman, Jan-Bernard C.; Knegtering, Henderikus; Aleman, Andre

    2016-01-01

    Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar

  16. Brain-inspired Stochastic Models and Implementations

    KAUST Repository

    Al-Shedivat, Maruan

    2015-05-12

    One of the approaches to building artificial intelligence (AI) is to decipher the princi- ples of the brain function and to employ similar mechanisms for solving cognitive tasks, such as visual perception or natural language understanding, using machines. The recent breakthrough, named deep learning, demonstrated that large multi-layer networks of arti- ficial neural-like computing units attain remarkable performance on some of these tasks. Nevertheless, such artificial networks remain to be very loosely inspired by the brain, which rich structures and mechanisms may further suggest new algorithms or even new paradigms of computation. In this thesis, we explore brain-inspired probabilistic mechanisms, such as neural and synaptic stochasticity, in the context of generative models. The two questions we ask here are: (i) what kind of models can describe a neural learning system built of stochastic components? and (ii) how can we implement such systems e ̆ciently? To give specific answers, we consider two well known models and the corresponding neural architectures: the Naive Bayes model implemented with a winner-take-all spiking neural network and the Boltzmann machine implemented in a spiking or non-spiking fashion. We propose and analyze an e ̆cient neuromorphic implementation of the stochastic neu- ral firing mechanism and study the e ̄ects of synaptic unreliability on learning generative energy-based models implemented with neural networks.

  17. Modulating conscious movement intention by noninvasive brain stimulation and the underlying neural mechanisms.

    Science.gov (United States)

    Douglas, Zachary H; Maniscalco, Brian; Hallett, Mark; Wassermann, Eric M; He, Biyu J

    2015-05-06

    Conscious intention is a fundamental aspect of the human experience. Despite long-standing interest in the basis and implications of intention, its underlying neurobiological mechanisms remain poorly understood. Using high-definition transcranial DC stimulation (tDCS), we observed that enhancing spontaneous neuronal excitability in both the angular gyrus and the primary motor cortex caused the reported time of conscious movement intention to be ∼60-70 ms earlier. Slow brain waves recorded ∼2-3 s before movement onset, as well as hundreds of milliseconds after movement onset, independently correlated with the modulation of conscious intention by brain stimulation. These brain activities together accounted for 81% of interindividual variability in the modulation of movement intention by brain stimulation. A computational model using coupled leaky integrator units with biophysically plausible assumptions about the effect of tDCS captured the effects of stimulation on both neural activity and behavior. These results reveal a temporally extended brain process underlying conscious movement intention that spans seconds around movement commencement. Copyright © 2015 Douglas et al.

  18. The relation of ongoing brain activity, evoked neural responses, and cognition

    Directory of Open Access Journals (Sweden)

    Sepideh Sadaghiani

    2010-06-01

    Full Text Available Ongoing brain activity has been observed since the earliest neurophysiological recordings and is found over a wide range of temporal and spatial scales. It is characterized by remarkably large spontaneous modulations. Here, we review evidence for the functional role of these ongoing activity fluctuations and argue that they constitute an essential property of the neural architecture underlying cognition. The role of spontaneous activity fluctuations is probably best understood when considering both their spatiotemporal structure and their functional impact on cognition. We first briefly argue against a ‘segregationist’ view on ongoing activity, both in time and space, countering this view with an emphasis on integration within a hierarchical spatiotemporal organization of intrinsic activity. We then highlight the flexibility and context-sensitivity of intrinsic functional connectivity that suggest its involvement in functionally relevant information processing. This role in information processing is pursued by reviewing how ongoing brain activity interacts with afferent and efferent information exchange of the brain with its environment. We focus on the relationship between the variability of ongoing and evoked brain activity, and review recent reports that tie ongoing brain activity fluctuations to variability in human perception and behavior. Finally, these observations are discussed within the framework of the free-energy principle which – applied to human brain function - provides a theoretical account for a non-random, coordinated interaction of ongoing and evoked activity in perception and behaviour.

  19. Oscillatory neural representations in the sensory thalamus predict neuropathic pain relief by deep brain stimulation.

    Science.gov (United States)

    Huang, Yongzhi; Green, Alexander L; Hyam, Jonathan; Fitzgerald, James; Aziz, Tipu Z; Wang, Shouyan

    2018-01-01

    Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Brain region-specific expression of MeCP2 isoforms correlates with DNA methylation within Mecp2 regulatory elements.

    Directory of Open Access Journals (Sweden)

    Carl O Olson

    Full Text Available 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

  1. Emergence of Convolutional Neural Network in Future Medicine: Why and How. A Review on Brain Tumor Segmentation

    Science.gov (United States)

    Alizadeh Savareh, Behrouz; Emami, Hassan; Hajiabadi, Mohamadreza; Ghafoori, Mahyar; Majid Azimi, Seyed

    2018-03-01

    Manual analysis of brain tumors magnetic resonance images is usually accompanied by some problem. Several techniques have been proposed for the brain tumor segmentation. This study will be focused on searching popular databases for related studies, theoretical and practical aspects of Convolutional Neural Network surveyed in brain tumor segmentation. Based on our findings, details about related studies including the datasets used, evaluation parameters, preferred architectures and complementary steps analyzed. Deep learning as a revolutionary idea in image processing, achieved brilliant results in brain tumor segmentation too. This can be continuing until the next revolutionary idea emerging.

  2. Brain Region–Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin–Induced Inflammation

    Science.gov (United States)

    Silverman, Harold A; Dancho, Meghan; Regnier-Golanov, Angelique; Nasim, Mansoor; Ochani, Mahendar; Olofsson, Peder S; Ahmed, Mohamed; Miller, Edmund J; Chavan, Sangeeta S; Golanov, Eugene; Metz, Christine N; Tracey, Kevin J; Pavlov, Valentin A

    2014-01-01

    Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune–brain communication, including the impact of peripheral inflammation on brain region–specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels), remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum and thalamus in mice after an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of interleukin (IL)-1β, IL-6 and other cytokines and brain region–specific increases in Il1b (the highest increase, relative to basal level, was in cortex; the lowest increase was in cerebellum) and Il6 (highest increase in cerebellum; lowest increase in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat ) mRNA expression was decreased in the striatum, acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus, and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation and are of interest for designing future antiinflammatory approaches. PMID:25299421

  3. Species-Specific Mechanisms of Neuron Subtype Specification Reveal Evolutionary Plasticity of Amniote Brain Development

    Directory of Open Access Journals (Sweden)

    Tadashi Nomura

    2018-03-01

    Full Text Available Summary: Highly ordered brain architectures in vertebrates consist of multiple neuron subtypes with specific neuronal connections. However, the origin of and evolutionary changes in neuron specification mechanisms remain unclear. Here, we report that regulatory mechanisms of neuron subtype specification are divergent in developing amniote brains. In the mammalian neocortex, the transcription factors (TFs Ctip2 and Satb2 are differentially expressed in layer-specific neurons. In contrast, these TFs are co-localized in reptilian and avian dorsal pallial neurons. Multi-potential progenitors that produce distinct neuronal subtypes commonly exist in the reptilian and avian dorsal pallium, whereas a cis-regulatory element of avian Ctip2 exhibits attenuated transcription suppressive activity. Furthermore, the neuronal subtypes distinguished by these TFs are not tightly associated with conserved neuronal connections among amniotes. Our findings reveal the evolutionary plasticity of regulatory gene functions that contribute to species differences in neuronal heterogeneity and connectivity in developing amniote brains. : Neuronal heterogeneity is essential for assembling intricate neuronal circuits. Nomura et al. find that species-specific transcriptional mechanisms underlie diversities of excitatory neuron subtypes in mammalian and non-mammalian brains. Species differences in neuronal subtypes and connections suggest functional plasticity of regulatory genes for neuronal specification during amniote brain evolution. Keywords: Ctip2, Satb2, multi-potential progenitors, transcriptional regulation, neuronal connectivity

  4. Modeling of Malachite Green Removal from Aqueous Solutions by Nanoscale Zerovalent Zinc Using Artificial Neural Network

    Directory of Open Access Journals (Sweden)

    Wenqian Ruan

    2017-12-01

    Full Text Available The commercially available nanoscale zerovalent zinc (nZVZ was used as an adsorbent for the removal of malachite green (MG from aqueous solutions. This material was characterized by X-ray diffraction and X-ray photoelectron spectroscopy. The advanced experimental design tools were adopted to study the effect of process parameters (viz. initial pH, temperature, contact time and initial concentration and to reduce number of trials and cost. Response surface methodology and rapidly developing artificial intelligence technologies, i.e., artificial neural network coupled with particle swarm optimization (ANN-PSO and artificial neural network coupled with genetic algorithm (ANN-GA were employed for predicting the optimum process variables and obtaining the maximum removal efficiency of MG. The results showed that the removal efficiency predicted by ANN-GA (94.12% was compatible with the experimental value (90.72%. Furthermore, the Langmuir isotherm was found to be the best model to describe the adsorption of MG onto nZVZ, while the maximum adsorption capacity was calculated to be 1000.00 mg/g. The kinetics for adsorption of MG onto nZVZ was found to follow the pseudo-second-order kinetic model. Thermodynamic parameters (ΔG0, ΔH0 and ΔS0 were calculated from the Van’t Hoff plot of lnKc vs. 1/T in order to discuss the removal mechanism of MG.

  5. A new perspective on behavioral inconsistency and neural noise in aging: Compensatory speeding of neural communication

    Directory of Open Access Journals (Sweden)

    S. Lee Hong

    2012-09-01

    Full Text Available This paper seeks to present a new perspective on the aging brain. Here, we make connections between two key phenomena of brain aging: 1 increased neural noise or random background activity; and 2 slowing of brain activity. Our perspective proposes the possibility that the slowing of neural processing due to decreasing nerve conduction velocities leads to a compensatory speeding of neuron firing rates. These increased firing rates lead to a broader distribution of power in the frequency spectrum of neural oscillations, which we propose, can just as easily be interpreted as neural noise. Compensatory speeding of neural activity, as we present, is constrained by the: A availability of metabolic energy sources; and B competition for frequency bandwidth needed for neural communication. We propose that these constraints lead to the eventual inability to compensate for age-related declines in neural function that are manifested clinically as deficits in cognition, affect, and motor behavior.

  6. A role for adult TLX-positive neural stem cells in learning and behaviour.

    Science.gov (United States)

    Zhang, Chun-Li; Zou, Yuhua; He, Weimin; Gage, Fred H; Evans, Ronald M

    2008-02-21

    Neurogenesis persists in the adult brain and can be regulated by a plethora of external stimuli, such as learning, memory, exercise, environment and stress. Although newly generated neurons are able to migrate and preferentially incorporate into the neural network, how these cells are molecularly regulated and whether they are required for any normal brain function are unresolved questions. The adult neural stem cell pool is composed of orphan nuclear receptor TLX-positive cells. Here, using genetic approaches in mice, we demonstrate that TLX (also called NR2E1) regulates adult neural stem cell proliferation in a cell-autonomous manner by controlling a defined genetic network implicated in cell proliferation and growth. Consequently, specific removal of TLX from the adult mouse brain through inducible recombination results in a significant reduction of stem cell proliferation and a marked decrement in spatial learning. In contrast, the resulting suppression of adult neurogenesis does not affect contextual fear conditioning, locomotion or diurnal rhythmic activities, indicating a more selective contribution of newly generated neurons to specific cognitive functions.

  7. Zinc and platelet membrane microviscosity in Alzheimer's disease

    African Journals Online (AJOL)

    zinc in AD patients, a recent study has contradicted this ... Atthough AD is seen as a disease of the brain, there is mounting evidence that ... membrane damage in the in vitro system.tI Zinc also .... who showed that 15 AD patients receiving dietary ... Onset 01 AlzheImer's dIsease: Influence of genes and environmental factors ...

  8. A neural link between affective understanding and interpersonal attraction

    Science.gov (United States)

    Anders, Silke; de Jong, Roos; Beck, Christian; Haynes, John-Dylan; Ethofer, Thomas

    2016-01-01

    Being able to comprehend another person’s intentions and emotions is essential for successful social interaction. However, it is currently unknown whether the human brain possesses a neural mechanism that attracts people to others whose mental states they can easily understand. Here we show that the degree to which a person feels attracted to another person can change while they observe the other’s affective behavior, and that these changes depend on the observer’s confidence in having correctly understood the other’s affective state. At the neural level, changes in interpersonal attraction were predicted by activity in the reward system of the observer’s brain. Importantly, these effects were specific to individual observer–target pairs and could not be explained by a target’s general attractiveness or expressivity. Furthermore, using multivoxel pattern analysis (MVPA), we found that neural activity in the reward system of the observer’s brain varied as a function of how well the target’s affective behavior matched the observer’s neural representation of the underlying affective state: The greater the match, the larger the brain’s intrinsic reward signal. Taken together, these findings provide evidence that reward-related neural activity during social encounters signals how well an individual’s “neural vocabulary” is suited to infer another person’s affective state, and that this intrinsic reward might be a source of changes in interpersonal attraction. PMID:27044071

  9. Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory.

    Science.gov (United States)

    Censor, Nitzan; Cohen, Leonardo G

    2011-01-01

    In the last two decades, there has been a rapid development in the research of the physiological brain mechanisms underlying human motor learning and memory. While conventional memory research performed on animal models uses intracellular recordings, microfusion of protein inhibitors to specific brain areas and direct induction of focal brain lesions, human research has so far utilized predominantly behavioural approaches and indirect measurements of neural activity. Repetitive transcranial magnetic stimulation (rTMS), a safe non-invasive brain stimulation technique, enables the study of the functional role of specific cortical areas by evaluating the behavioural consequences of selective modulation of activity (excitation or inhibition) on memory generation and consolidation, contributing to the understanding of the neural substrates of motor learning. Depending on the parameters of stimulation, rTMS can also facilitate learning processes, presumably through purposeful modulation of excitability in specific brain regions. rTMS has also been used to gain valuable knowledge regarding the timeline of motor memory formation, from initial encoding to stabilization and long-term retention. In this review, we summarize insights gained using rTMS on the physiological and neural mechanisms of human motor learning and memory. We conclude by suggesting possible future research directions, some with direct clinical implications.

  10. Brain Injury Expands the Numbers of Neural Stem Cells and Progenitors in the SVZ by Enhancing Their Responsiveness to EGF

    Directory of Open Access Journals (Sweden)

    Dhivyaa Alagappan

    2009-04-01

    Full Text Available There is an increase in the numbers of neural precursors in the SVZ (subventricular zone after moderate ischaemic injuries, but the extent of stem cell expansion and the resultant cell regeneration is modest. Therefore our studies have focused on understanding the signals that regulate these processes towards achieving a more robust amplification of the stem/progenitor cell pool. The goal of the present study was to evaluate the role of the EGFR [EGF (epidermal growth factor receptor] in the regenerative response of the neonatal SVZ to hypoxic/ischaemic injury. We show that injury recruits quiescent cells in the SVZ to proliferate, that they divide more rapidly and that there is increased EGFR expression on both putative stem cells and progenitors. With the amplification of the precursors in the SVZ after injury there is enhanced sensitivity to EGF, but not to FGF (fibroblast growth factor-2. EGF-dependent SVZ precursor expansion, as measured using the neurosphere assay, is lost when the EGFR is pharmacologically inhibited, and forced expression of a constitutively active EGFR is sufficient to recapitulate the exaggerated proliferation of the neural stem/progenitors that is induced by hypoxic/ischaemic brain injury. Cumulatively, our results reveal that increased EGFR signalling precedes that increase in the abundance of the putative neural stem cells and our studies implicate the EGFR as a key regulator of the expansion of SVZ precursors in response to brain injury. Thus modulating EGFR signalling represents a potential target for therapies to enhance brain repair from endogenous neural precursors following hypoxic/ischaemic and other brain injuries.

  11. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Zinc release contributes to hypoglycemia-induced neuronal death.

    Science.gov (United States)

    Suh, Sang Won; Garnier, Philippe; Aoyama, Koji; Chen, Yongmei; Swanson, Raymond A

    2004-08-01

    Neurons exposed to zinc exhibit activation of poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme that normally participates in DNA repair but promotes cell death when extensively activated. Endogenous, vesicular zinc in brain is released to the extracellular space under conditions causing neuronal depolarization. Here, we used a rat model of insulin-induced hypoglycemia to assess the role of zinc release in PARP-1 activation and neuronal death after severe hypoglycemia. Zinc staining with N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) showed depletion of presynaptic vesicular zinc from hippocampal mossy fiber terminals and accumulation of weakly bound zinc in hippocampal CA1 cell bodies after severe hypoglycemia. Intracerebroventricular injection of the zinc chelator calcium ethylene-diamine tetraacetic acid (CaEDTA) blocked the zinc accumulation and significantly reduced hypoglycemia-induced neuronal death. CaEDTA also attenuated the accumulation of poly(ADP-ribose), the enzymatic product of PARP-1, in hippocampal neurons. These results suggest that zinc translocation is an intermediary step linking hypoglycemia to PARP-1 activation and neuronal death.

  13. Dysfunction of Rapid Neural Adaptation in Dyslexia.

    Science.gov (United States)

    Perrachione, Tyler K; Del Tufo, Stephanie N; Winter, Rebecca; Murtagh, Jack; Cyr, Abigail; Chang, Patricia; Halverson, Kelly; Ghosh, Satrajit S; Christodoulou, Joanna A; Gabrieli, John D E

    2016-12-21

    Identification of specific neurophysiological dysfunctions resulting in selective reading difficulty (dyslexia) has remained elusive. In addition to impaired reading development, individuals with dyslexia frequently exhibit behavioral deficits in perceptual adaptation. Here, we assessed neurophysiological adaptation to stimulus repetition in adults and children with dyslexia for a wide variety of stimuli, spoken words, written words, visual objects, and faces. For every stimulus type, individuals with dyslexia exhibited significantly diminished neural adaptation compared to controls in stimulus-specific cortical areas. Better reading skills in adults and children with dyslexia were associated with greater repetition-induced neural adaptation. These results highlight a dysfunction of rapid neural adaptation as a core neurophysiological difference in dyslexia that may underlie impaired reading development. Reduced neurophysiological adaptation may relate to prior reports of reduced behavioral adaptation in dyslexia and may reveal a difference in brain functions that ultimately results in a specific reading impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Syringe needle skull penetration reduces brain injuries and secondary inflammation following intracerebral neural stem cell transplantation

    OpenAIRE

    Gao, Mou; Dong, Qin; Zhang, Hongtian; Yang, Yang; Zhu, Jianwei; Yang, Zhijun; Xu, Minhui; Xu, Ruxiang

    2017-01-01

    Intracerebral neural stem cell (NSC) transplantation is beneficial for delivering stem cell grafts effectively, however, this approach may subsequently result in brain injury and secondary inflammation. To reduce the risk of promoting brain injury and secondary inflammation, two methods were compared in the present study. Murine skulls were penetrated using a drill on the left side and a syringe needle on the right. Mice were randomly divided into three groups (n=84/group): Group A, receiving...

  15. Design, construction, and analysis of specific zinc finger nucleases for microphthalmia - associate transcription factor

    Directory of Open Access Journals (Sweden)

    Wenwen Wang

    2012-08-01

    Full Text Available This work studied the design, construction, and cleavage analysis of zinc finger nucleases (ZFNs that could cut the specific sequences within microphthalmia - associate transcription factor (mitfa of zebra fish. The target site and ZFPs were selected and designed with zinc finger tools, while the ZFPs were synthesized using DNAWorks and two-step PCR. The ZFNs were constructed, expressed, purified, and analyzed in vitro. As expected, the designed ZFNs could create a double-stand break (DSB at the target site in vitro. The DNAWorks, two-step PCR, and an optimized process of protein expression were firstly induced in the construction of ZFNs successfully, which was an effective and simplified protocol. These results could be useful for further application of ZFNs - mediated gene targeting.

  16. Zinc blotting assay for detection of zinc binding prolamin in barley (Hordeum vulgare) grain

    DEFF Research Database (Denmark)

    Uddin, Mohammad Nasir; Nielsen, Ane Langkilde-Lauesen; Vincze, Eva

    2014-01-01

    In plants, zinc is commonly found bound to proteins. In barley (Hordeum vulgare), major storage proteins are alcohol-soluble prolamins known as hordeins, and some of them have the potential to bind or store zinc. 65Zn overlay and blotting techniques have been widely used for detecting zinc......-binding protein. However, to our knowledge so far this zinc blotting assay has never been applied to detect a prolamin fraction in barley grains. A radioactive zinc (65ZnCl2) blotting technique was optimized to detect zinc-binding prolamins, followed by development of an easy-to-follow nonradioactive colorimetric...... zinc blotting method with a zinc-sensing dye, dithizone. Hordeins were extracted from mature barley grain, separated by SDS-PAGE, blotted on a membrane, renatured, overlaid, and probed with zinc; subsequently, zinc-binding specificity of certain proteins was detected either by autoradiography or color...

  17. Zinc monotherapy increases serum brain-derived neurotrophic factor (BDNF) levels and decreases depressive symptoms in overweight or obese subjects: a double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Solati, Zahra; Jazayeri, Shima; Tehrani-Doost, Mehdi; Mahmoodianfard, Salma; Gohari, Mahmood Reza

    2015-05-01

    Previous studies have shown a positive effect of zinc as an adjunctive therapy on reducing depressive symptoms. However, to our knowledge, no study has examined the effect of zinc monotherapy on mood. The aim of the present study was to determine the effects of zinc monotherapy on depressive symptoms and serum brain-derived neurotrophic factor (BDNF) levels in overweight or obese subjects. Fifty overweight or obese subjects were randomly assigned into two groups and received either 30 mg zinc or placebo daily for 12 weeks. At baseline and post-intervention, depression severity was assessed using Beck depression inventory II (BDI II), and serum BDNF and zinc levels were determined by enzyme-linked immunosorbent assay and atomic absorption spectrophotometry, respectively. The trial was completed with 46 subjects. After a 12-week supplementation, serum zinc and BDNF levels increased significantly in the zinc-supplemented group compared with the placebo group. BDI scores declined in both the groups at the end of the study, but reduction in the zinc-supplemented group was significantly higher than the placebo group. More analysis revealed that following supplementation, BDI scores decreased in subgroup of subjects with depressive symptoms (BDI ≥ 10) (n = 30), but did not change in the subgroup of non-depressed subjects (BDI BDNF levels and depression severity in all participants. Interestingly, a significant positive correlation was found between serum BDNF and zinc levels at baseline. Zinc monotherapy improves mood in overweight or obese subjects most likely through increasing BDNF levels.

  18. Neural Correlates of Single- and Dual-Task Walking in the Real World

    Directory of Open Access Journals (Sweden)

    Sara Pizzamiglio

    2017-09-01

    Full Text Available Recent developments in mobile brain-body imaging (MoBI technologies have enabled studies of human locomotion where subjects are able to move freely in more ecologically valid scenarios. In this study, MoBI was employed to describe the behavioral and neurophysiological aspects of three different commonly occurring walking conditions in healthy adults. The experimental conditions were self-paced walking, walking while conversing with a friend and lastly walking while texting with a smartphone. We hypothesized that gait performance would decrease with increased cognitive demands and that condition-specific neural activation would involve condition-specific brain areas. Gait kinematics and high density electroencephalography (EEG were recorded whilst walking around a university campus. Conditions with dual tasks were accompanied by decreased gait performance. Walking while conversing was associated with an increase of theta (θ and beta (β neural power in electrodes located over left-frontal and right parietal regions, whereas walking while texting was associated with a decrease of β neural power in a cluster of electrodes over the frontal-premotor and sensorimotor cortices when compared to walking whilst conversing. In conclusion, the behavioral “signatures” of common real-life activities performed outside the laboratory environment were accompanied by differing frequency-specific neural “biomarkers”. The current findings encourage the study of the neural biomarkers of disrupted gait control in neurologically impaired patients.

  19. Neural stem cells improve neuronal survival in cultured postmortem brain tissue from aged and Alzheimer patients

    NARCIS (Netherlands)

    Wu, L.; Sluiter, A.A.; Guo, Ho Fu; Balesar, R. A.; Swaab, D. F.; Zhou, Jiang Ning; Verwer, R. W H

    Neurodegenerative diseases are progressive and incurable and are becoming ever more prevalent. To study whether neural stem cell can reactivate or rescue functions of impaired neurons in the human aging and neurodegenerating brain, we co-cultured postmortem slices from Alzheimer patients and control

  20. Cysteine-rich intestinal protein binds zinc during transmucosal zinc transport

    International Nuclear Information System (INIS)

    Hempe, J.M.; Cousins, R.J.

    1991-01-01

    The mechanism of zinc absorption has not been delineated, but kinetic studies show that both passive and carrier-mediated processes are involved. The authors have identified a low molecular mass zinc-binding protein in the soluble fraction of rat intestinal mucosa that could function as an intracellular zinc carrier. The protein was not detected in liver or pancreas, suggesting a role specific to the intestine. The protein binds zinc during transmucosal zinc transport and shows signs of saturation at higher luminal zinc concentrations, characteristics consistent with a role in carrier-mediated zinc absorption. Microsequence analysis of the protein purified by gel-filtration HPCL and SDS/PAGE showed complete identity within the first 41 N-terminal amino acids with the deduced protein sequence of cysteine-rich intestinal protein. These investigators showed that the gene for this protein is developmentally regulated in neonates during the suckling period, conserved in many vertebrate species, and predominantly expressed in the small intestine. Cysteine-rich intestinal protein contains a recently identified conserved sequence of histidine and cysteine residues, the LIM motif, which our results suggest confers metal-binding properties that are important for zinc transport and/or functions of this micronutrient

  1. Where in the brain is morality? Everywhere and maybe nowhere.

    Science.gov (United States)

    Young, Liane; Dungan, James

    2012-01-01

    The neuroscience of morality has focused on how morality works and where it is in the brain. In tackling these questions, researchers have taken both domain-specific and domain-general approaches-searching for neural substrates and systems dedicated to moral cognition versus characterizing the contributions of domain-general processes. Where in the brain is morality? On one hand, morality is made up of complex cognitive processes, deployed across many domains and housed all over the brain. On the other hand, no neural substrate or system that uniquely supports moral cognition has been found. In this review, we will discuss early assumptions of domain-specificity in moral neuroscience as well as subsequent investigations of domain-general contributions, taking emotion and social cognition (i.e., theory of mind) as case studies. Finally, we will consider possible cognitive accounts of a domain-specific morality: Does uniquely moral cognition exist?

  2. Chronic zinc exposure decreases the surface expression of NR2A-containing NMDA receptors in cultured hippocampal neurons.

    Directory of Open Access Journals (Sweden)

    Jia Zhu

    Full Text Available Zinc distributes widely in the central nervous system, especially in the hippocampus, amygdala and cortex. The dynamic balance of zinc is critical for neuronal functions. Zinc modulates the activity of N-methyl-D-aspartate receptors (NMDARs through the direct inhibition and various intracellular signaling pathways. Abnormal NMDAR activities have been implicated in the aetiology of many brain diseases. Sustained zinc accumulation in the extracellular fluid is known to link to pathological conditions. However, the mechanism linking this chronic zinc exposure and NMDAR dysfunction is poorly understood.We reported that chronic zinc exposure reduced the numbers of NR1 and NR2A clusters in cultured hippocampal pyramidal neurons. Whole-cell and synaptic NR2A-mediated currents also decreased. By contrast, zinc did not affect NR2B, suggesting that chronic zinc exposure specifically influences NR2A-containg NMDARs. Surface biotinylation indicated that zinc exposure attenuated the membrane expression of NR1 and NR2A, which might arise from to the dissociation of the NR2A-PSD-95-Src complex.Chronic zinc exposure perturbs the interaction of NR2A to PSD-95 and causes the disorder of NMDARs in hippocampal neurons, suggesting a novel action of zinc distinct from its acute effects on NMDAR activity.

  3. Neural Plasticity following Abacus Training in Humans: A Review and Future Directions

    Directory of Open Access Journals (Sweden)

    Yongxin Li

    2016-01-01

    Full Text Available The human brain has an enormous capacity to adapt to a broad variety of environmental demands. Previous studies in the field of abacus training have shown that this training can induce specific changes in the brain. However, the neural mechanism underlying these changes remains elusive. Here, we reviewed the behavioral and imaging findings of comparisons between abacus experts and average control subjects and focused on changes in activation patterns and changes in brain structure. Finally, we noted the limitations and the future directions of this field. We concluded that although current studies have provided us with information about the mechanisms of abacus training, more research on abacus training is needed to understand its neural impact.

  4. Zinc Improves Cognitive and Neuronal Dysfunction During Aluminium-Induced Neurodegeneration.

    Science.gov (United States)

    Singla, Neha; Dhawan, D K

    2017-01-01

    Metals are considered as important components of a physiologically active cell, and imbalance in their levels can lead to various diseased conditions. Aluminium (Al) is an environmental neurotoxicant, which is etiologically related to several neurodegenerative disorders like Alzheimer's, whereas zinc (Zn) is an essential trace element that regulates a large number of metabolic processes in the brain. The objective of the present study was to understand whether Zn provides any physiological protection during Al-induced neurodegeneration. Male Sprague Dawley rats weighing 140-160 g received either aluminium chloride (AlCl 3 ) orally (100 mg/kg b.wt./day), zinc sulphate (ZnSO 4 ) in drinking water (227 mg/L) or combined treatment of aluminium and zinc for 8 weeks. Al treatment resulted in a significant decline in the cognitive behaviour of rats, whereas zinc supplementation caused an improvement in various neurobehavior parameters. Further, Al exposure decreased (p ≤ 0.001) the levels of neurotransmitters, acetylcholinesterase activity, but increased (p ≤ 0.001) the levels of L-citrulline as well as activities of nitric oxide and monoamine oxidase in the brain. However, zinc administration to Al-treated animals increased the levels of neurotransmitters and regulated the altered activities of brain markers. Western blot of tau, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ubiquitin, α-synuclein and Hsp 70 were also found to be elevated after Al exposure, which however were reversed following Zn treatment. Al treatment also revealed alterations in neurohistoarchitecture in the form of loss of pyramidal and Purkinje cells, which were improved upon zinc co-administration. Therefore, the present study demonstrates that zinc improves cognitive functions by regulating α-synuclein and APP-mediated molecular pathways during aluminium-induced neurodegeneration.

  5. Localization and functional analysis of the insect-specific RabX4 in the brain of Bombyx mori.

    Science.gov (United States)

    Uno, Tomohide; Furutani, Masayuki; Sakamoto, Katsuhiko; Uno, Yuichi; Kanamaru, Kengo; Mizoguchi, Akira; Hiragaki, Susumu; Takeda, Makio

    2017-09-01

    Rab proteins are small monomeric GTPases/GTP-binding proteins, which form the largest branch of the Ras superfamily. The different Rab GTPases are localized to the cytosolic face of specific intracellular membranes, where they function as regulators of distinct steps in membrane trafficking. RabX4 is an insect-specific Rab protein that has no close homolog in vertebrates. There is little information about insect-specific Rab proteins. RabX4 was expressed in Escherichia coli and subsequently purified. Antibodies against Bombyx mori RabX4 were produced in rabbits for western immunoblotting and immunohistochemistry. Western blotting of neural tissues revealed a single band, at approximately 26 kD. RabX4-like immunohistochemical reactivity was restricted to neurons of the pars intercerebralis and dorsolateral protocerebrum in the brain. Further immunohistochemical analysis revealed that RabX4 colocalized with Rab6 and bombyxin in the corpus allatum, a neuronal organ that secretes neuropeptides synthesized in the brain into the hemolymph. RabX4 expression in the frontal ganglion, part of the insect stomatogastric nervous system that is found in most insect orders, was restricted to two neurons on the outer region and did not colocalize with allatotropin or Rab6. Furthermore, RNA interference of RabX4 decreased bombyxin expression levels in the brain. These findings suggest that RabX4 is involved in the neurosecretion of a secretory organ in Bombyx mori. © 2017 Wiley Periodicals, Inc.

  6. Decreased astroglial cell adhesion and proliferation on zinc oxide nanoparticle polyurethane composites

    Directory of Open Access Journals (Sweden)

    Justin T Seil

    2008-11-01

    Full Text Available Justin T Seil, Thomas J WebsterLaboratory for Nanomedicine Research, Division of Engineering, Brown University, Providence, RI, USAAbstract: Nanomaterials offer a number of properties that are of interest to the field of neural tissue engineering. Specifically, materials that exhibit nanoscale surface dimensions have been shown to promote neuron function while simultaneously minimizing the activity of cells such as astrocytes that inhibit central nervous system regeneration. Studies demonstrating enhanced neural tissue regeneration in electrical fields through the use of conductive materials have led to interest in piezoelectric materials (or those materials which generate a transient electrical potential when mechanically deformed such as zinc oxide (ZnO. It has been speculated that ZnO nanoparticles possess increased piezoelectric properties over ZnO micron particles. Due to this promise in neural applications, the objective of the present in vitro study was, for the first time, to assess the activity of astroglial cells on ZnO nanoparticle polymer composites. ZnO nanoparticles embedded in polyurethane were analyzed via scanning electron microscopy to evaluate nanoscale surface features of the composites. The surface chemistry was characterized via X-ray photoelectron spectroscopy. Astroglial cell response was evaluated based on cell adhesion and proliferation. Astrocyte adhesion was significantly reduced on ZnO nanoparticle/polyurethane (PU composites with a weight ratio of 50:50 (PU:ZnO wt.%, 75:25 (PU:ZnO wt.%, and 90:10 (PU:ZnO wt.% in comparison to pure PU. The successful production of ZnO nanoparticle composite scaffolds suitable for decreasing astroglial cell density demonstrates their potential as a nerve guidance channel material with greater efficiency than what may be available today.Keywords: zinc oxide, nanoparticles, astrocytes, neural tissue, nervous system, biomaterials

  7. Brain-specific enhancers for cell-based therapy

    Science.gov (United States)

    Visel, Axel; Rubenstein, John L.R.; Chen, Ying-Jiun; Pennacchio, Len A.; Vogt, Daniel; Nicholas, Cory; Kriegstein, Arnold

    2018-04-24

    Herein are described a set of novel specific human enhancers for specific forebrain cell types used to study and select for human neural progenitor cells. This approach enables the ability to generate interneurons from human ES, iPS and iN cells, making them available for human transplantation and for molecular/cellular analyzes. These approaches are also directly applicable to generating other neuronal cell types, such as cortical and striatal projection neurons, which have implications for many human diseases.

  8. Neural Oscillations and Synchrony in Brain Dysfunction and Neuropsychiatric Disorders: It's About Time.

    Science.gov (United States)

    Mathalon, Daniel H; Sohal, Vikaas S

    2015-08-01

    Neural oscillations are rhythmic fluctuations over time in the activity or excitability of single neurons, local neuronal populations or "assemblies," and/or multiple regionally distributed neuronal assemblies. Synchronized oscillations among large numbers of neurons are evident in electrocorticographic, electroencephalographic, magnetoencephalographic, and local field potential recordings and are generally understood to depend on inhibition that paces assemblies of excitatory neurons to produce alternating temporal windows of reduced and increased excitability. Synchronization of neural oscillations is supported by the extensive networks of local and long-range feedforward and feedback bidirectional connections between neurons. Here, we review some of the major methods and measures used to characterize neural oscillations, with a focus on gamma oscillations. Distinctions are drawn between stimulus-independent oscillations recorded during resting states or intervals between task events, stimulus-induced oscillations that are time locked but not phase locked to stimuli, and stimulus-evoked oscillations that are both time and phase locked to stimuli. Synchrony of oscillations between recording sites, and between the amplitudes and phases of oscillations of different frequencies (cross-frequency coupling), is described and illustrated. Molecular mechanisms underlying gamma oscillations are also reviewed. Ultimately, understanding the temporal organization of neuronal network activity, including interactions between neural oscillations, is critical for elucidating brain dysfunction in neuropsychiatric disorders.

  9. Neural Tube Defects

    Science.gov (United States)

    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

  10. Chimera states in brain networks: Empirical neural vs. modular fractal connectivity

    Science.gov (United States)

    Chouzouris, Teresa; Omelchenko, Iryna; Zakharova, Anna; Hlinka, Jaroslav; Jiruska, Premysl; Schöll, Eckehard

    2018-04-01

    Complex spatiotemporal patterns, called chimera states, consist of coexisting coherent and incoherent domains and can be observed in networks of coupled oscillators. The interplay of synchrony and asynchrony in complex brain networks is an important aspect in studies of both the brain function and disease. We analyse the collective dynamics of FitzHugh-Nagumo neurons in complex networks motivated by its potential application to epileptology and epilepsy surgery. We compare two topologies: an empirical structural neural connectivity derived from diffusion-weighted magnetic resonance imaging and a mathematically constructed network with modular fractal connectivity. We analyse the properties of chimeras and partially synchronized states and obtain regions of their stability in the parameter planes. Furthermore, we qualitatively simulate the dynamics of epileptic seizures and study the influence of the removal of nodes on the network synchronizability, which can be useful for applications to epileptic surgery.

  11. Transformation of zinc hydroxide chloride monohydrate to crystalline zinc oxide.

    Science.gov (United States)

    Moezzi, Amir; Cortie, Michael; McDonagh, Andrew

    2016-04-25

    Thermal decomposition of layered zinc hydroxide double salts provides an interesting alternative synthesis for particles of zinc oxide. Here, we examine the sequence of changes occurring as zinc hydroxide chloride monohydrate (Zn5(OH)8Cl2·H2O) is converted to crystalline ZnO by thermal decomposition. The specific surface area of the resultant ZnO measured by BET was 1.3 m(2) g(-1). A complicating and important factor in this process is that the thermal decomposition of zinc hydroxide chloride is also accompanied by the formation of volatile zinc-containing species under certain conditions. We show that this volatile compound is anhydrous ZnCl2 and its formation is moisture dependent. Therefore, control of atmospheric moisture is an important consideration that affects the overall efficiency of ZnO production by this process.

  12. Novel paths towards neural cellular products for neurological disorders.

    Science.gov (United States)

    Daadi, Marcel M

    2011-11-01

    The prospect of using neural cells derived from stem cells or from reprogrammed adult somatic cells provides a unique opportunity in cell therapy and drug discovery for developing novel strategies for brain repair. Cell-based therapeutic approaches for treating CNS afflictions caused by disease or injury aim to promote structural repair of the injured or diseased neural tissue, an outcome currently not achieved by drug therapy. Preclinical research in animal models of various diseases or injuries report that grafts of neural cells enhance endogenous repair, provide neurotrophic support to neurons undergoing degeneration and replace lost neural cells. In recent years, the sources of neural cells for treating neurological disorders have been rapidly expanding and in addition to offering therapeutic potential, neural cell products hold promise for disease modeling and drug discovery use. Specific neural cell types have been derived from adult or fetal brain, from human embryonic stem cells, from induced pluripotent stem cells and directly transdifferentiated from adult somatic cells, such as skin cells. It is yet to be determined if the latter approach will evolve into a paradigm shift in the fields of stem cell research and regenerative medicine. These multiple sources of neural cells cover a wide spectrum of safety that needs to be balanced with efficacy to determine the viability of the cellular product. In this article, we will review novel sources of neural cells and discuss current obstacles to developing them into viable cellular products for treating neurological disorders.

  13. Brain-to-text: Decoding spoken phrases from phone representations in the brain

    Directory of Open Access Journals (Sweden)

    Christian eHerff

    2015-06-01

    Full Text Available It has long been speculated whether communication between humans and machines based on natural speech related cortical activity is possible. Over the past decade, studies have suggested that it is feasible to recognize isolated aspects of speech from neural signals, such as auditory features, phones or one of a few isolated words. However, until now it remained an unsolved challenge to decode continuously spoken speech from the neural substrate associated with speech and language processing. Here, we show for the first time that continuously spoken speech can be decoded into the expressed words from intracranial electrocorticographic (ECoG recordings. Specifically, we implemented a system, which we call Brain-To-Text that models single phones, employs techniques from automatic speech recognition (ASR, and thereby transforms brain activity while speaking into the corresponding textual representation. Our results demonstrate that our system achieved word error rates as low as 25% and phone error rates below 50%. Additionally, our approach contributes to the current understanding of the neural basis of continuous speech production by identifying those cortical regions that hold substantial information about individual phones. In conclusion, the Brain-To-Text system described in this paper represents an important step towards human-machine communication based on imagined speech.

  14. Air pollution and children: neural and tight junction antibodies and combustion metals, the role of barrier breakdown and brain immunity in neurodegeneration.

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Vojdani, Aristo; Blaurock-Busch, Eleonore; Busch, Yvette; Friedle, Albrecht; Franco-Lira, Maricela; Sarathi-Mukherjee, Partha; Martínez-Aguirre, Xavier; Park, Su-Bin; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

    2015-01-01

    Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. In the Mexico City Metropolitan Area (MCMA) megacity, children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.

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

    Science.gov (United States)

    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

    2015-07-16

    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.

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

    Directory of Open Access Journals (Sweden)

    Wei Lei

    2015-07-01

    Full Text Available 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.

  17. Learning speaker-specific characteristics with a deep neural architecture.

    Science.gov (United States)

    Chen, Ke; Salman, Ahmad

    2011-11-01

    Speech signals convey various yet mixed information ranging from linguistic to speaker-specific information. However, most of acoustic representations characterize all different kinds of information as whole, which could hinder either a speech or a speaker recognition (SR) system from producing a better performance. In this paper, we propose a novel deep neural architecture (DNA) especially for learning speaker-specific characteristics from mel-frequency cepstral coefficients, an acoustic representation commonly used in both speech recognition and SR, which results in a speaker-specific overcomplete representation. In order to learn intrinsic speaker-specific characteristics, we come up with an objective function consisting of contrastive losses in terms of speaker similarity/dissimilarity and data reconstruction losses used as regularization to normalize the interference of non-speaker-related information. Moreover, we employ a hybrid learning strategy for learning parameters of the deep neural networks: i.e., local yet greedy layerwise unsupervised pretraining for initialization and global supervised learning for the ultimate discriminative goal. With four Linguistic Data Consortium (LDC) benchmarks and two non-English corpora, we demonstrate that our overcomplete representation is robust in characterizing various speakers, no matter whether their utterances have been used in training our DNA, and highly insensitive to text and languages spoken. Extensive comparative studies suggest that our approach yields favorite results in speaker verification and segmentation. Finally, we discuss several issues concerning our proposed approach.

  18. Brain-derived neurotrophic factor and addiction: Pathological versus therapeutic effects on drug seeking

    NARCIS (Netherlands)

    Barker, J.M.; Taylor, J.R.; de Vries, T.J.; Peters, J.

    2015-01-01

    Many abused drugs lead to changes in endogenous brain-derived neurotrophic factor (BDNF) expression in neural circuits responsible for addictive behaviors. BDNF is a known molecular mediator of memory consolidation processes, evident at both behavioral and neurophysiological levels. Specific neural

  19. Behavioral impairments in animal models for zinc deficiency

    Directory of Open Access Journals (Sweden)

    Simone eHagmeyer

    2015-01-01

    Full Text Available Apart from teratogenic and pathological effects of zinc deficiency such as the occurrence of skin lesions, anorexia, growth retardation, depressed wound healing, altered immune function, impaired night vision, and alterations in taste and smell acuity, characteristic behavioral changes in animal models and human patients suffering from zinc deficiency have been observed. Given that it is estimated that about 17% of the worldwide population are at risk for zinc deficiency and that zinc deficiency is associated with a variety of brain disorders and disease states in humans, it is of major interest to investigate, how these behavioral changes will affect the individual and a putative course of a disease. Thus, here, we provide a state of the art overview about the behavioral phenotypes observed in various models of zinc deficiency, among them environmentally produced zinc deficient animals as well as animal models based on a genetic alteration of a particular zinc homeostasis gene. Finally, we compare the behavioral phenotypes to the human condition of mild to severe zinc deficiency and provide a model, how zinc deficiency that is associated with many neurodegenerative and neuropsychological disorders might modify the disease pathologies.

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

    Directory of Open Access Journals (Sweden)

    Seung-Schik Yoo

    Full Text Available 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.

  1. Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage.

    Directory of Open Access Journals (Sweden)

    Kyeung Min Joo

    Full Text Available Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.

  2. Resting-state brain activity in the motor cortex reflects task-induced activity: A multi-voxel pattern analysis.

    Science.gov (United States)

    Kusano, Toshiki; Kurashige, Hiroki; Nambu, Isao; Moriguchi, Yoshiya; Hanakawa, Takashi; Wada, Yasuhiro; Osu, Rieko

    2015-08-01

    It has been suggested that resting-state brain activity reflects task-induced brain activity patterns. In this study, we examined whether neural representations of specific movements can be observed in the resting-state brain activity patterns of motor areas. First, we defined two regions of interest (ROIs) to examine brain activity associated with two different behavioral tasks. Using multi-voxel pattern analysis with regularized logistic regression, we designed a decoder to detect voxel-level neural representations corresponding to the tasks in each ROI. Next, we applied the decoder to resting-state brain activity. We found that the decoder discriminated resting-state neural activity with accuracy comparable to that associated with task-induced neural activity. The distribution of learned weighted parameters for each ROI was similar for resting-state and task-induced activities. Large weighted parameters were mainly located on conjunctive areas. Moreover, the accuracy of detection was higher than that for a decoder whose weights were randomly shuffled, indicating that the resting-state brain activity includes multi-voxel patterns similar to the neural representation for the tasks. Therefore, these results suggest that the neural representation of resting-state brain activity is more finely organized and more complex than conventionally considered.

  3. Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation

    Science.gov (United States)

    Lenoir, Magalie

    2012-01-01

    Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2–6 s) increased (30–70 μM or 6–14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (−20–40 μM or 5–10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological

  4. Neural Basis of Brain Dysfunction Produced by Early Sleep Problems

    Directory of Open Access Journals (Sweden)

    Jun Kohyama

    2016-01-01

    Full Text Available There is a wealth of evidence that disrupted sleep and circadian rhythms, which are common in modern society even during the early stages of life, have unfavorable effects on brain function. Altered brain function can cause problem behaviors later in life, such as truancy from or dropping out of school, quitting employment, and committing suicide. In this review, we discuss findings from several large cohort studies together with recent results of a cohort study using the marshmallow test, which was first introduced in the 1960s. This test assessed the ability of four-year-olds to delay gratification and showed how this ability correlated with success later in life. The role of the serotonergic system in sleep and how this role changes with age are also discussed. The serotonergic system is involved in reward processing and interactions with the dorsal striatum, ventral striatum, and the prefrontal cortex are thought to comprise the neural basis for behavioral patterns that are affected by the quantity, quality, and timing of sleep early in life.

  5. Neural Basis of Brain Dysfunction Produced by Early Sleep Problems.

    Science.gov (United States)

    Kohyama, Jun

    2016-01-29

    There is a wealth of evidence that disrupted sleep and circadian rhythms, which are common in modern society even during the early stages of life, have unfavorable effects on brain function. Altered brain function can cause problem behaviors later in life, such as truancy from or dropping out of school, quitting employment, and committing suicide. In this review, we discuss findings from several large cohort studies together with recent results of a cohort study using the marshmallow test, which was first introduced in the 1960s. This test assessed the ability of four-year-olds to delay gratification and showed how this ability correlated with success later in life. The role of the serotonergic system in sleep and how this role changes with age are also discussed. The serotonergic system is involved in reward processing and interactions with the dorsal striatum, ventral striatum, and the prefrontal cortex are thought to comprise the neural basis for behavioral patterns that are affected by the quantity, quality, and timing of sleep early in life.

  6. The brain as a "hyper-network": the key role of neural networks as main producers of the integrated brain actions especially via the "broadcasted" neuroconnectomics.

    Science.gov (United States)

    Agnati, Luigi F; Marcoli, Manuela; Maura, Guido; Woods, Amina; Guidolin, Diego

    2018-06-01

    Investigations of brain complex integrative actions should consider beside neural networks, glial, extracellular molecular, and fluid channels networks. The present paper proposes that all these networks are assembled into the brain hyper-network that has as fundamental components, the tetra-partite synapses, formed by neural, glial, and extracellular molecular networks. Furthermore, peri-synaptic astrocytic processes by modulating the perviousness of extracellular fluid channels control the signals impinging on the tetra-partite synapses. It has also been surmised that global signalling via astrocytes networks and highly pervasive signals, such as electromagnetic fields (EMFs), allow the appropriate integration of the various networks especially at crucial nodes level, the tetra-partite synapses. As a matter of fact, it has been shown that astrocytes can form gap-junction-coupled syncytia allowing intercellular communication characterised by a rapid and possibly long-distance transfer of signals. As far as the EMFs are concerned, the concept of broadcasted neuroconnectomics (BNC) has been introduced to describe highly pervasive signals involved in resetting the information handling of brain networks at various miniaturisation levels. In other words, BNC creates, thanks to the EMFs, generated especially by neurons, different assemblages among the various networks forming the brain hyper-network. Thus, it is surmised that neuronal networks are the "core components" of the brain hyper-network that has as special "nodes" the multi-facet tetra-partite synapses. Furthermore, it is suggested that investigations on the functional plasticity of multi-partite synapses in response to BNC can be the background for a new understanding and perhaps a new modelling of brain morpho-functional organisation and integrative actions.

  7. Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting.

    Directory of Open Access Journals (Sweden)

    K Ryan Wessells

    Full Text Available BACKGROUND: Adequate zinc nutrition is essential for adequate growth, immunocompetence and neurobehavioral development, but limited information on population zinc status hinders the expansion of interventions to control zinc deficiency. The present analyses were conducted to: (1 estimate the country-specific prevalence of inadequate zinc intake; and (2 investigate relationships between country-specific estimated prevalence of dietary zinc inadequacy and dietary patterns and stunting prevalence. METHODOLOGY AND PRINCIPAL FINDINGS: National food balance sheet data were obtained from the Food and Agriculture Organization of the United Nations. Country-specific estimated prevalence of inadequate zinc intake were calculated based on the estimated absorbable zinc content of the national food supply, International Zinc Nutrition Consultative Group estimated physiological requirements for absorbed zinc, and demographic data obtained from United Nations estimates. Stunting data were obtained from a recent systematic analysis based on World Health Organization growth standards. An estimated 17.3% of the world's population is at risk of inadequate zinc intake. Country-specific estimated prevalence of inadequate zinc intake was negatively correlated with the total energy and zinc contents of the national food supply and the percent of zinc obtained from animal source foods, and positively correlated with the phytate: zinc molar ratio of the food supply. The estimated prevalence of inadequate zinc intake was correlated with the prevalence of stunting (low height-for-age in children under five years of age (r = 0.48, P<0.001. CONCLUSIONS AND SIGNIFICANCE: These results, which indicate that inadequate dietary zinc intake may be fairly common, particularly in Sub-Saharan Africa and South Asia, allow inter-country comparisons regarding the relative likelihood of zinc deficiency as a public health problem. Data from these analyses should be used to determine

  8. Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides.

    Science.gov (United States)

    Di Scala, Coralie; Yahi, Nouara; Flores, Alessandra; Boutemeur, Sonia; Kourdougli, Nazim; Chahinian, Henri; Fantini, Jacques

    2016-02-01

    Growing evidence supports a role for brain gangliosides in the pathogenesis of neurodegenerative diseases including Alzheimer's and Parkinson's. Recently we deciphered the ganglioside-recognition code controlling specific ganglioside binding to Alzheimer's β-amyloid (Aβ1-42) peptide and Parkinson's disease-associated protein α-synuclein. Cracking this code allowed us to engineer a short chimeric Aβ/α-synuclein peptide that recognizes all brain gangliosides. Here we show that ganglioside-deprived neural cells do no longer sustain the formation of zinc-sensitive amyloid pore channels induced by either Aβ1-42 or α-synuclein, as assessed by single-cell Ca(2+) fluorescence microscopy. Thus, amyloid channel formation, now considered a key step in neurodegeneration, is a ganglioside-dependent process. Nanomolar concentrations of chimeric peptide competitively inhibited amyloid pore formation induced by Aβ1-42 or α-synuclein in cultured neural cells. Moreover, this peptide abrogated the intracellular calcium increases induced by Parkinson's-associated mutant forms of α-synuclein (A30P, E46K and A53T). The chimeric peptide also prevented the deleterious effects of Aβ1-42 on synaptic vesicle trafficking and decreased the Aβ1-42-induced impairment of spontaneous activity in rat hippocampal slices. Taken together, these data show that the chimeric peptide has broad anti-amyloid pore activity, suggesting that a common therapeutic strategy based on the prevention of amyloid-ganglioside interactions is a reachable goal for both Alzheimer's and Parkinson's diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Color selection and location selection in ERPs : differences, similarities and 'neural specificity'

    NARCIS (Netherlands)

    Lange, J.J.; Wijers, A.A.; Mulder, L.J.M.; Mulder, G.

    It was hypothesized that color selection consists of two stages. The first stage represents a feature specific selection in neural populations specialized in processing color. The second stage constitutes feature non-specific selections, related to executive attentional processes and/or motor

  10. Sandwich masking eliminates both visual awareness of faces and face-specific brain activity through a feedforward mechanism.

    Science.gov (United States)

    Harris, Joseph A; Wu, Chien-Te; Woldorff, Marty G

    2011-06-07

    It is generally agreed that considerable amounts of low-level sensory processing of visual stimuli can occur without conscious awareness. On the other hand, the degree of higher level visual processing that occurs in the absence of awareness is as yet unclear. Here, event-related potential (ERP) measures of brain activity were recorded during a sandwich-masking paradigm, a commonly used approach for attenuating conscious awareness of visual stimulus content. In particular, the present study used a combination of ERP activation contrasts to track both early sensory-processing ERP components and face-specific N170 ERP activations, in trials with versus without awareness. The electrophysiological measures revealed that the sandwich masking abolished the early face-specific N170 neural response (peaking at ~170 ms post-stimulus), an effect that paralleled the abolition of awareness of face versus non-face image content. Furthermore, however, the masking appeared to render a strong attenuation of earlier feedforward visual sensory-processing signals. This early attenuation presumably resulted in insufficient information being fed into the higher level visual system pathways specific to object category processing, thus leading to unawareness of the visual object content. These results support a coupling of visual awareness and neural indices of face processing, while also demonstrating an early low-level mechanism of interference in sandwich masking.

  11. The Effect of Salts in Promoting Specific and Competitive Interactions between Zinc Finger Proteins and Metals

    Science.gov (United States)

    Li, Gongyu; Yuan, Siming; Zheng, Shihui; Chen, Yuting; Zheng, Zhen; Liu, Yangzhong; Huang, Guangming

    2017-12-01

    Specific protein-metal interactions (PMIs) fulfill essential functions in cells and organic bodies, and activation of these functions in vivo are mostly modulated by the complex environmental factors, including pH value, small biomolecules, and salts. Specifically, the role of salts in promoting specific PMIs and their competition among various metals has remained untapped mainly due to the difficulty to distinguish nonspecific PMIs from specific PMIs by classic spectroscopic techniques. Herein, we report Hofmeister salts differentially promote the specific PMIs by combining nanoelectrospray ionization mass spectrometry and spectroscopic techniques (fluorescence measurement and circular dichroism). Furthermore, to explore the influence of salts in competitive binding between metalloproteins and various metals, we designed a series of competitive experiments and applied to a well-defined model system, the competitive binding of zinc (II) and arsenic (III) to holo-promyelocytic leukemia protein (PML). These experiments not only provided new insights at the molecular scale as complementary to previous NMR and spectroscopic results, but also deduced the relative binding ability between zinc finger proteins and metals at the molecular scale, which avoids the mass spectrometric titration-based determination of binding constants that is frequently affected and often degraded by variable solution conditions including salt contents. [Figure not available: see fulltext.

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

    Science.gov (United States)

    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. Fluoxetine coupled with zinc in a chronic mild stress model of depression: Providing a reservoir for optimum zinc signaling and neuronal remodeling.

    Science.gov (United States)

    Omar, Nesreen Nabil; Tash, Reham Fathy

    2017-09-01

    Recently, depression has been envisioned as more than an alteration in neurotransmitters centered around receptor signaling pathways. Consequently, the precise mechanisms of selective serotonin reuptake inhibitor (SSRI) antidepressant drugs such as fluoxetine are being revisited. Zinc is a trace element that has been long implicated in the psychopathology and therapy of depression. Zinc has been found to be sequestered and dispensed during stress and inflammation through a family of proteins called metallothioneins (MTs). In addition, MTs are well known for their antioxidant and therefore cytoprotective action. Changes in MTs, their upstream regulators and downstream effectors in response to fluoxetine have not been yet studied. The aim of the present study is to examine whether depression-induced changes in protein levels and mRNA levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), MTs, antioxidant defensive enzyme heme oxygenase (HO-1), zinc-specific receptor GPR39 and brain derived neurotrophic factor (BDNF) in the hippocampus can be reversed by fluoxetine treatment, zinc supplementation or a combination of the two. The present study investigated the effect of chronic (4weeks) combined treatment with zinc hydroaspartate (15mg/kg) and fluoxetine (10mg/kg) on a chronic mild stress model (CMS) in male Sprague-Dawley rats. Hippocampal mRNA and protein levels of Nrf2, HO-1, MTs, GPR39 (protein level only) and BDNF were significantly higher in response to a combined therapy of fluoxetine and zinc than to either monotherapy. Additionally, HO-1 and MTs gene expression was correlated with that of Nrf2 in the FLX-only group. Fluoxetine therapy activated the expression of MTs and HO-1 through an Nrf2-dependent pathway. When FLX was escorted by zinc, activated MTs had a positive impact on BDNF through the zinc signaling receptor GPR39, resulting in general improvement in neuronal plasticity as well as reduction of neuronal atrophy and neuronal cell loss. Copyright

  14. Zinc in the prevention of Fe2initiated lipid and protein oxidation

    Directory of Open Access Journals (Sweden)

    M. PAOLA ZAGO

    2000-01-01

    Full Text Available In the present study we characterized the capacity of zinc to protect lipids and proteins from Fe2+-initiated oxidative damage. The effects of zinc on lipid oxidation were investigated in liposomes composed of brain phosphatidylcholine (PC and phosphatidylserine (PS at a molar relationship of 60:40 (PC:PS, 60:40. Lipid oxidation was evaluated as the oxidation of cis-parinaric acid or as the formation of 2-thiobarbituric acid-reactive substances (TBARS. Zinc protected liposomes from Fe2+ (2.5-50 muM-supported lipid oxidation. However, zinc (50 muM did not prevent the oxidative inactivation of glutamine synthelase and glucose 6-phosphate dehydrogenase when rat brain superntants were oxidized in the presence of 5 muM Fe2+ and 0.5 mM H2O2 .We also studied the interactions of zinc with epicatechin in the prevention of liid oxidation in liposomes. The simulaneous addition of 0.5 muM epicatechin (EC and 50 muM zinc or EC separately. Zinc (50 muM also protecte liposomes from the stimulatory effect of aluminum on Fe2+-initiated lipid oxidation. Zinc could play an important role as an antioxidant in biological systems, replacing iron and other metals with pro-oxidant activity from binding sites and interacting with other components of the oxidant defense system.

  15. Neural Networks for the Beginner.

    Science.gov (United States)

    Snyder, Robin M.

    Motivated by the brain, neural networks are a right-brained approach to artificial intelligence that is used to recognize patterns based on previous training. In practice, one would not program an expert system to recognize a pattern and one would not train a neural network to make decisions from rules; but one could combine the best features of…

  16. Neural Control of a Tracking Task via Attention-Gated Reinforcement Learning for Brain-Machine Interfaces.

    Science.gov (United States)

    Wang, Yiwen; Wang, Fang; Xu, Kai; Zhang, Qiaosheng; Zhang, Shaomin; Zheng, Xiaoxiang

    2015-05-01

    Reinforcement learning (RL)-based brain machine interfaces (BMIs) enable the user to learn from the environment through interactions to complete the task without desired signals, which is promising for clinical applications. Previous studies exploited Q-learning techniques to discriminate neural states into simple directional actions providing the trial initial timing. However, the movements in BMI applications can be quite complicated, and the action timing explicitly shows the intention when to move. The rich actions and the corresponding neural states form a large state-action space, imposing generalization difficulty on Q-learning. In this paper, we propose to adopt attention-gated reinforcement learning (AGREL) as a new learning scheme for BMIs to adaptively decode high-dimensional neural activities into seven distinct movements (directional moves, holdings and resting) due to the efficient weight-updating. We apply AGREL on neural data recorded from M1 of a monkey to directly predict a seven-action set in a time sequence to reconstruct the trajectory of a center-out task. Compared to Q-learning techniques, AGREL could improve the target acquisition rate to 90.16% in average with faster convergence and more stability to follow neural activity over multiple days, indicating the potential to achieve better online decoding performance for more complicated BMI tasks.

  17. How age of bilingual exposure can change the neural systems for language in the developing brain: a functional near infrared spectroscopy investigation of syntactic processing in monolingual and bilingual children.

    Science.gov (United States)

    Jasinska, K K; Petitto, L A

    2013-10-01

    Is the developing bilingual brain fundamentally similar to the monolingual brain (e.g., neural resources supporting language and cognition)? Or, does early-life bilingual language experience change the brain? If so, how does age of first bilingual exposure impact neural activation for language? We compared how typically-developing bilingual and monolingual children (ages 7-10) and adults recruit brain areas during sentence processing using functional Near Infrared Spectroscopy (fNIRS) brain imaging. Bilingual participants included early-exposed (bilingual exposure from birth) and later-exposed individuals (bilingual exposure between ages 4-6). Both bilingual children and adults showed greater neural activation in left-hemisphere classic language areas, and additionally, right-hemisphere homologues (Right Superior Temporal Gyrus, Right Inferior Frontal Gyrus). However, important differences were observed between early-exposed and later-exposed bilinguals in their earliest-exposed language. Early bilingual exposure imparts fundamental changes to classic language areas instead of alterations to brain regions governing higher cognitive executive functions. However, age of first bilingual exposure does matter. Later-exposed bilinguals showed greater recruitment of the prefrontal cortex relative to early-exposed bilinguals and monolinguals. The findings provide fascinating insight into the neural resources that facilitate bilingual language use and are discussed in terms of how early-life language experiences can modify the neural systems underlying human language processing. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. BWR zinc addition Sourcebook

    International Nuclear Information System (INIS)

    Garcia, Susan E.; Giannelli, Joseph F.; Jarvis, Alfred J.

    2014-01-01

    Boiling Water Reactors (BWRs) have been injecting zinc into the primary coolant via the reactor feedwater system for over 25 years for the purpose of controlling primary system radiation fields. The BWR zinc injection process has evolved since the initial application at the Hope Creek Nuclear Station in 1986. Key transitions were from the original natural zinc oxide (NZO) to depleted zinc oxide (DZO), and from active zinc injection of a powdered zinc oxide slurry (pumped systems) to passive injection systems (zinc pellet beds). Zinc addition has continued through various chemistry regimes changes, from normal water chemistry (NWC) to hydrogen water chemistry (HWC) and HWC with noble metals (NobleChem™) for mitigation of intergranular stress corrosion cracking (IGSCC) of reactor internals and primary system piping. While past reports published by the Electric Power Research Institute (EPRI) document specific industry experience related to these topics, the Zinc Sourcebook was prepared to consolidate all of the experience gained over the past 25 years. The Zinc Sourcebook will benefit experienced BWR Chemistry, Operations, Radiation Protection and Engineering personnel as well as new people entering the nuclear power industry. While all North American BWRs implement feedwater zinc injection, a number of other BWRs do not inject zinc. This Sourcebook will also be a valuable resource to plants considering the benefits of zinc addition process implementation, and to gain insights on industry experience related to zinc process control and best practices. This paper presents some of the highlights from the Sourcebook. (author)

  19. A Neural Region of Abstract Working Memory

    Science.gov (United States)

    Cowan, Nelson; Li, Dawei; Moffitt, Amanda; Becker, Theresa M.; Martin, Elizabeth A.; Saults, J. Scott; Christ, Shawn E.

    2011-01-01

    Over 350 years ago, Descartes proposed that the neural basis of consciousness must be a brain region in which sensory inputs are combined. Using fMRI, we identified at least one such area for working memory, the limited information held in mind, described by William James as the trailing edge of consciousness. Specifically, a region in the left…

  20. Function of FEZF1 during early neural differentiation of human embryonic stem cells.

    Science.gov (United States)

    Liu, Xin; Su, Pei; Lu, Lisha; Feng, Zicen; Wang, Hongtao; Zhou, Jiaxi

    2018-01-01

    The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1 (FEZF1) as a potential regulator of early human neural development. FEZF1 is rapidly up-regulated during neural differentiation in hESCs and expressed before PAX6, a well-established marker of early human neural induction. We generated FEZF1-knockout H1 hESC lines using CRISPR-CAS9 technology and found that depletion of FEZF1 abrogates neural differentiation of hESCs. Moreover, loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. However, enforced expression of FEZF1 itself fails to drive neural differentiation in hESCs, suggesting that FEZF1 is necessary but not sufficient for neural differentiation from hESCs. Taken together, our findings identify one of the earliest regulators expressed upon neural induction and provide insight into early neural development in human.

  1. Systemic treatment of focal brain injury in the rat by human umbilical cord blood cells being at different level of neural commitment.

    Science.gov (United States)

    Gornicka-Pawlak, El Bieta; Janowski, Miroslaw; Habich, Aleksandra; Jablonska, Anna; Drela, Katarzyna; Kozlowska, Hanna; Lukomska, Barbara; Sypecka, Joanna; Domanska-Janik, Krystyna

    2011-01-01

    The aim of the study was to evaluate therapeutic effectiveness of intra-arterial infusion of human umbilical cord blood (HUCB) derived cells at different stages of their neural conversion. Freshly isolated mononuclear cells (D-0), neurally directed progenitors (D-3) and neural-like stem cells derived from umbilical cord blood (NSC) were compared. Focal brain damage was induced in rats by stereotactic injection of ouabain into dorsolateral striatum Three days later 10(7) of different subsets of HUCB cells were infused into the right internal carotid artery. Following surgery rats were housed in enriched environment for 30 days. Behavioral assessment consisted of tests for sensorimotor deficits (walking beam, rotarod, vibrissae elicited forelimb placing, apomorphine induced rotations), cognitive impairments (habit learning and object recognition) and exploratory behavior (open field). Thirty days after surgery the lesion volume was measured and the presence of donor cells was detected in the brain at mRNA level. At the same time immunohistochemical analysis of brain tissue was performed to estimate the local tissue response of ouabain injured rats and its modulation after HUCB cells systemic treatment. Functional effects of different subsets of cord blood cells shared substantial diversity in various behavioral tests. An additional analysis showed that D-0 HUCB cells were the most effective in functional restoration and reduction of brain lesion volume. None of transplanted cord blood derived cell fractions were detected in rat's brains at 30(th) day after treatment. This may suggest that the mechanism(s) underlying positive effects of HUCB derived cell may concern the other than direct neural cell supplementation. In addition increased immunoreactivity of markers indicating local cells proliferation and migration suggests stimulation of endogenous reparative processes by HUCB D-0 cell interarterial infusion.

  2. Facing changes and changing faces in adolescence: a new model for investigating adolescent-specific interactions between pubertal, brain and behavioral development.

    Science.gov (United States)

    Scherf, K Suzanne; Behrmann, Marlene; Dahl, Ronald E

    2012-04-01

    Adolescence is a time of dramatic physical, cognitive, emotional, and social changes as well as a time for the development of many social-emotional problems. These characteristics raise compelling questions about accompanying neural changes that are unique to this period of development. Here, we propose that studying adolescent-specific changes in face processing and its underlying neural circuitry provides an ideal model for addressing these questions. We also use this model to formulate new hypotheses. Specifically, pubertal hormones are likely to increase motivation to master new peer-oriented developmental tasks, which will in turn, instigate the emergence of new social/affective components of face processing. We also predict that pubertal hormones have a fundamental impact on the re-organization of neural circuitry supporting face processing and propose, in particular, that, the functional connectivity, or temporal synchrony, between regions of the face-processing network will change with the emergence of these new components of face processing in adolescence. Finally, we show how this approach will help reveal why adolescence may be a period of vulnerability in brain development and suggest how it could lead to prevention and intervention strategies that facilitate more adaptive functional interactions between regions within the broader social information processing network. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Facing changes and changing faces in adolescence: A new model for investigating adolescent-specific interactions between pubertal, brain and behavioral development

    Science.gov (United States)

    Scherf, K. Suzanne; Behrmann, Marlene; Dahl, Ronald E.

    2015-01-01

    Adolescence is a time of dramatic physical, cognitive, emotional, and social changes as well as a time for the development of many social-emotional problems. These characteristics raise compelling questions about accompanying neural changes that are unique to this period of development. Here, we propose that studying adolescent-specific changes in face processing and its underlying neural circuitry provides an ideal model for addressing these questions. We also use this model to formulate new hypotheses. Specifically, pubertal hormones are likely to increase motivation to master new peer-oriented developmental tasks, which will in turn, instigate the emergence of new social/affective components of face processing. We also predict that pubertal hormones have a fundamental impact on the reorganization of neural circuitry supporting face processing and propose, in particular, that, the functional connectivity, or temporal synchrony, between regions of the face-processing network will change with the emergence of these new components of face processing in adolescence. Finally, we show how this approach will help reveal why adolescence may be a period of vulnerability in brain development and suggest how it could lead to prevention and intervention strategies that facilitate more adaptive functional interactions between regions within the broader social information processing network. PMID:22483070

  4. The Neural Correlates of Abstract and Concrete Words: Evidence from Brain-Damaged Patients

    OpenAIRE

    Papagno, Costanza; Martello, Giorgia; Mattavelli, Giulia

    2013-01-01

    Neuropsychological and activation studies on the neural correlates of abstract and concrete words have produced contrasting results. The present study explores the anatomical substrates of abstract/concrete words in 22 brain-damaged patients with a single vascular lesion either in the right or left hemisphere. One hundred and twenty (60 concrete and 60 abstract) noun triplets were used for a semantic similarity judgment task. We found a significant interaction in word type × group since left ...

  5. Sleep fragmentation alters brain energy metabolism without modifying hippocampal electrophysiological response to novelty exposure

    KAUST Repository

    Baud, Maxime O.; Parafita, Julia; Nguyen, Audrey; Magistretti, Pierre J.; Petit, Jean-Marie

    2016-01-01

    © 2016 European Sleep Research Society. Sleep is viewed as a fundamental restorative function of the brain, but its specific role in neural energy budget remains poorly understood. Sleep deprivation dampens brain energy metabolism and impairs

  6. Hypnosis and imaging of the living human brain.

    Science.gov (United States)

    Landry, Mathieu; Raz, Amir

    2015-01-01

    Over more than two decades, studies using imaging techniques of the living human brain have begun to explore the neural correlates of hypnosis. The collective findings provide a gripping, albeit preliminary, account of the underlying neurobiological mechanisms involved in hypnotic phenomena. While substantial advances lend support to different hypotheses pertaining to hypnotic modulation of attention, control, and monitoring processes, the complex interactions among the many mediating variables largely hinder our ability to isolate robust commonalities across studies. The present account presents a critical integrative synthesis of neuroimaging studies targeting hypnosis as a function of suggestion. Specifically, hypnotic induction without task-specific suggestion is examined, as well as suggestions concerning sensation and perception, memory, and ideomotor response. The importance of carefully designed experiments is highlighted to better tease apart the neural correlates that subserve hypnotic phenomena. Moreover, converging findings intimate that hypnotic suggestions seem to induce specific neural patterns. These observations propose that suggestions may have the ability to target focal brain networks. Drawing on evidence spanning several technological modalities, neuroimaging studies of hypnosis pave the road to a more scientific understanding of a dramatic, yet largely evasive, domain of human behavior.

  7. Doctor, Teacher, and Stethoscope: Neural Representation of Different Types of Semantic Relations.

    Science.gov (United States)

    Xu, Yangwen; Wang, Xiaosha; Wang, Xiaoying; Men, Weiwei; Gao, Jia-Hong; Bi, Yanchao

    2018-03-28

    Concepts can be related in many ways. They can belong to the same taxonomic category (e.g., "doctor" and "teacher," both in the category of people) or be associated with the same event context (e.g., "doctor" and "stethoscope," both associated with medical scenarios). How are these two major types of semantic relations coded in the brain? We constructed stimuli from three taxonomic categories (people, manmade objects, and locations) and three thematic categories (school, medicine, and sports) and investigated the neural representations of these two dimensions using representational similarity analyses in human participants (10 men and nine women). In specific regions of interest, the left anterior temporal lobe (ATL) and the left temporoparietal junction (TPJ), we found that, whereas both areas had significant effects of taxonomic information, the taxonomic relations had stronger effects in the ATL than in the TPJ ("doctor" and "teacher" closer in ATL neural activity), with the reverse being true for thematic relations ("doctor" and "stethoscope" closer in TPJ neural activity). A whole-brain searchlight analysis revealed that widely distributed regions, mainly in the left hemisphere, represented the taxonomic dimension. Interestingly, the significant effects of the thematic relations were only observed after the taxonomic differences were controlled for in the left TPJ, the right superior lateral occipital cortex, and other frontal, temporal, and parietal regions. In summary, taxonomic grouping is a primary organizational dimension across distributed brain regions, with thematic grouping further embedded within such taxonomic structures. SIGNIFICANCE STATEMENT How are concepts organized in the brain? It is well established that concepts belonging to the same taxonomic categories (e.g., "doctor" and "teacher") share neural representations in specific brain regions. How concepts are associated in other manners (e.g., "doctor" and "stethoscope," which are thematically

  8. Brain entropy and human intelligence: A resting-state fMRI study

    Science.gov (United States)

    Calderone, Daniel; Morales, Leah J.

    2018-01-01

    Human intelligence comprises comprehension of and reasoning about an infinitely variable external environment. A brain capable of large variability in neural configurations, or states, will more easily understand and predict variable external events. Entropy measures the variety of configurations possible within a system, and recently the concept of brain entropy has been defined as the number of neural states a given brain can access. This study investigates the relationship between human intelligence and brain entropy, to determine whether neural variability as reflected in neuroimaging signals carries information about intellectual ability. We hypothesize that intelligence will be positively associated with entropy in a sample of 892 healthy adults, using resting-state fMRI. Intelligence is measured with the Shipley Vocabulary and WASI Matrix Reasoning tests. Brain entropy was positively associated with intelligence. This relation was most strongly observed in the prefrontal cortex, inferior temporal lobes, and cerebellum. This relationship between high brain entropy and high intelligence indicates an essential role for entropy in brain functioning. It demonstrates that access to variable neural states predicts complex behavioral performance, and specifically shows that entropy derived from neuroimaging signals at rest carries information about intellectual capacity. Future work in this area may elucidate the links between brain entropy in both resting and active states and various forms of intelligence. This insight has the potential to provide predictive information about adaptive behavior and to delineate the subdivisions and nature of intelligence based on entropic patterns. PMID:29432427

  9. Brain entropy and human intelligence: A resting-state fMRI study.

    Science.gov (United States)

    Saxe, Glenn N; Calderone, Daniel; Morales, Leah J

    2018-01-01

    Human intelligence comprises comprehension of and reasoning about an infinitely variable external environment. A brain capable of large variability in neural configurations, or states, will more easily understand and predict variable external events. Entropy measures the variety of configurations possible within a system, and recently the concept of brain entropy has been defined as the number of neural states a given brain can access. This study investigates the relationship between human intelligence and brain entropy, to determine whether neural variability as reflected in neuroimaging signals carries information about intellectual ability. We hypothesize that intelligence will be positively associated with entropy in a sample of 892 healthy adults, using resting-state fMRI. Intelligence is measured with the Shipley Vocabulary and WASI Matrix Reasoning tests. Brain entropy was positively associated with intelligence. This relation was most strongly observed in the prefrontal cortex, inferior temporal lobes, and cerebellum. This relationship between high brain entropy and high intelligence indicates an essential role for entropy in brain functioning. It demonstrates that access to variable neural states predicts complex behavioral performance, and specifically shows that entropy derived from neuroimaging signals at rest carries information about intellectual capacity. Future work in this area may elucidate the links between brain entropy in both resting and active states and various forms of intelligence. This insight has the potential to provide predictive information about adaptive behavior and to delineate the subdivisions and nature of intelligence based on entropic patterns.

  10. Traumatic brain injury causes long-term behavioral changes related to region-specific increases of cerebral blood flow.

    Science.gov (United States)

    Pöttker, Bruno; Stöber, Franziska; Hummel, Regina; Angenstein, Frank; Radyushkin, Konstantin; Goldschmidt, Jürgen; Schäfer, Michael K E

    2017-12-01

    Traumatic brain injury (TBI) is a leading cause of disability and death and survivors often suffer from long-lasting motor impairment, cognitive deficits, anxiety disorders and epilepsy. Few experimental studies have investigated long-term sequelae after TBI and relations between behavioral changes and neural activity patterns remain elusive. We examined these issues in a murine model of TBI combining histology, behavioral analyses and single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (CBF) as a proxy for neural activity. Adult C57Bl/6N mice were subjected to unilateral cortical impact injury and investigated at early (15-57 days after lesion, dal) and late (184-225 dal) post-traumatic time points. TBI caused pronounced tissue loss of the parietal cortex and subcortical structures and enduring neurological deficits. Marked perilesional astro- and microgliosis was found at 57 dal and declined at 225 dal. Motor and gait pattern deficits occurred at early time points after TBI and improved over the time. In contrast, impaired performance in the Morris water maze test and decreased anxiety-like behavior persisted together with an increased susceptibility to pentylenetetrazole-induced seizures suggesting alterations in neural activity patterns. Accordingly, SPECT imaging of CBF indicated asymmetric hemispheric baseline neural activity patterns. In the ipsilateral hemisphere, increased baseline neural activity was found in the amygdala. In the contralateral hemisphere, homotopic to the structural brain damage, the hippocampus and distinct cortex regions displayed increased baseline neural activity. Thus, regionally elevated CBF along with behavioral alterations indicate that increased neural activity is critically involved in the long-lasting consequences of TBI.

  11. Fatigue in multiple sclerosis: neural correlates and the role of non-invasive brain stimulation

    Directory of Open Access Journals (Sweden)

    Moussa A. Chalah

    2015-11-01

    Full Text Available Multiple sclerosis (MS is a chronic progressive inflammatory disease of the central nervous system and the major cause of non-traumatic disability in young adults. Fatigue is a frequent symptom reported by the majority of MS patients during their disease course and drastically af-fects their quality of life. Despite its significant prevalence and impact, the underlying patho-physiological mechanisms are not well elucidated. MS fatigue is still considered the result of multifactorial and complex constellations, and is commonly classified into primary fatigue related to the pathological changes of the disease itself, and secondary fatigue attributed to mimicking symptoms, comorbid sleep and mood disorders, and medications side effects. Data from neuroimaging, neurophysiology, neuroendocrine and neuroimmune studies have raised hypotheses regarding the origin of this symptom, some of which have succeeded in identifying an association between MS fatigue and structural or functional abnormalities within various brain networks. Hence, the aim of this work is to reappraise the neural correlates of MS fatigue and to discuss the rationale for the emergent use of noninvasive brain stimulation (NIBS techniques as potential treatments. This will include a presentation of the various NIBS modalities and a proposition of their potential mechanisms of action in this context. Specific issues related to the value of transcranial direct current stimulation will be addressed.

  12. "Binaural Rivalry": Dichotic Listening as a Tool for the Investigation of the Neural Correlate of Consciousness

    Science.gov (United States)

    Brancucci, Alfredo; Tommasi, Luca

    2011-01-01

    Since about two decades neuroscientists have systematically faced the problem of consciousness: the aim is to discover the neural activity specifically related to conscious perceptions, i.e. the biological properties of what philosophers call qualia. In this view, a neural correlate of consciousness (NCC) is a precise pattern of brain activity…

  13. Neural signature of behavioural inhibition in women with bulimia nervosa.

    Science.gov (United States)

    Skunde, Mandy; Walther, Stephan; Simon, Joe J; Wu, Mudan; Bendszus, Martin; Herzog, Wolfgang; Friederich, Hans-Christoph

    2016-08-01

    Impaired inhibitory control is considered a behavioural phenotype in patients with bulimia nervosa. However, the underlying neural correlates of impaired general and food-specific behavioural inhibition are largely unknown. Therefore, we investigated brain activation during the performance of behavioural inhibition to general and food-related stimuli in adults with bulimia nervosa. Women with bulimia and healthy control women underwent event-related fMRI while performing a general and a food-specific no-go task. We included 28 women with bulimia nervosa and 29 healthy control women in our study. On a neuronal level, we observed significant group differences in response to general no-go stimuli in women with bulimia nervosa with high symptom severity; compared with healthy controls, the patients showed reduced activation in the right sensorimotor area (postcentral gyrus, precentral gyrus) and right dorsal striatum (caudate nucleus, putamen). The present results are limited to adult women with bulimia nervosa. Furthermore, it remains unclear whether impaired behavioural inhibition in patients with this disorder are a cause or consequence of chronic illness. Our findings suggest that diminished frontostriatal brain activation in patients with bulimia nervosa contribute to the severity of binge eating symptoms. Gaining further insight into the neural mechanisms of behavioural inhibition problems in individuals with this disorder may inform brain-directed treatment approaches and the development of response inhibition training approaches to improve inhibitory control in patients with bulimia nervosa. The present study does not support greater behavioural and neural impairments to food-specific behavioural inhibition in these patients.

  14. Neural signature of behavioural inhibition in women with bulimia nervosa

    Science.gov (United States)

    Skunde, Mandy; Walther, Stephan; Simon, Joe J.; Wu, Mudan; Bendszus, Martin; Herzog, Wolfgang; Friederich, Hans-Christoph

    2016-01-01

    Background Impaired inhibitory control is considered a behavioural phenotype in patients with bulimia nervosa. However, the underlying neural correlates of impaired general and food-specific behavioural inhibition are largely unknown. Therefore, we investigated brain activation during the performance of behavioural inhibition to general and food-related stimuli in adults with bulimia nervosa. Methods Women with bulimia and healthy control women underwent event-related fMRI while performing a general and a food-specific no-go task. Results We included 28 women with bulimia nervosa and 29 healthy control women in our study. On a neuronal level, we observed significant group differences in response to general no-go stimuli in women with bulimia nervosa with high symptom severity; compared with healthy controls, the patients showed reduced activation in the right sensorimotor area (postcentral gyrus, precentral gyrus) and right dorsal striatum (caudate nucleus, putamen). Limitations The present results are limited to adult women with bulimia nervosa. Furthermore, it remains unclear whether impaired behavioural inhibition in patients with this disorder are a cause or consequence of chronic illness. Conclusion Our findings suggest that diminished frontostriatal brain activation in patients with bulimia nervosa contribute to the severity of binge eating symptoms. Gaining further insight into the neural mechanisms of behavioural inhibition problems in individuals with this disorder may inform brain-directed treatment approaches and the development of response inhibition training approaches to improve inhibitory control in patients with bulimia nervosa. The present study does not support greater behavioural and neural impairments to food-specific behavioural inhibition in these patients. PMID:27575858

  15. The Neural Basis of Typewriting: A Functional MRI Study.

    Science.gov (United States)

    Higashiyama, Yuichi; Takeda, Katsuhiko; Someya, Yoshiaki; Kuroiwa, Yoshiyuki; Tanaka, Fumiaki

    2015-01-01

    To investigate the neural substrate of typewriting Japanese words and to detect the difference between the neural substrate of typewriting and handwriting, we conducted a functional magnetic resonance imaging (fMRI) study in 16 healthy volunteers. All subjects were skillful touch typists and performed five tasks: a typing task, a writing task, a reading task, and two control tasks. Three brain regions were activated during both the typing and the writing tasks: the left superior parietal lobule, the left supramarginal gyrus, and the left premotor cortex close to Exner's area. Although typing and writing involved common brain regions, direct comparison between the typing and the writing task revealed greater left posteromedial intraparietal cortex activation in the typing task. In addition, activity in the left premotor cortex was more rostral in the typing task than in the writing task. These findings suggest that, although the brain circuits involved in Japanese typewriting are almost the same as those involved in handwriting, there are brain regions that are specific for typewriting.

  16. The Neural Basis of Typewriting: A Functional MRI Study.

    Directory of Open Access Journals (Sweden)

    Yuichi Higashiyama

    Full Text Available To investigate the neural substrate of typewriting Japanese words and to detect the difference between the neural substrate of typewriting and handwriting, we conducted a functional magnetic resonance imaging (fMRI study in 16 healthy volunteers. All subjects were skillful touch typists and performed five tasks: a typing task, a writing task, a reading task, and two control tasks. Three brain regions were activated during both the typing and the writing tasks: the left superior parietal lobule, the left supramarginal gyrus, and the left premotor cortex close to Exner's area. Although typing and writing involved common brain regions, direct comparison between the typing and the writing task revealed greater left posteromedial intraparietal cortex activation in the typing task. In addition, activity in the left premotor cortex was more rostral in the typing task than in the writing task. These findings suggest that, although the brain circuits involved in Japanese typewriting are almost the same as those involved in handwriting, there are brain regions that are specific for typewriting.

  17. Transcranial Magnetic Stimulation and Connectivity Mapping: Tools for Studying the Neural Bases of Brain Disorders

    OpenAIRE

    Hampson, M.; Hoffman, R. E.

    2010-01-01

    There has been an increasing emphasis on characterizing pathophysiology underlying psychiatric and neurological disorders in terms of altered neural connectivity and network dynamics. Transcranial magnetic stimulation (TMS) provides a unique opportunity for investigating connectivity in the human brain. TMS allows researchers and clinicians to directly stimulate cortical regions accessible to electromagnetic coils positioned on the scalp. The induced activation can then propagate through...

  18. A deep convolutional neural network-based automatic delineation strategy for multiple brain metastases stereotactic radiosurgery.

    Directory of Open Access Journals (Sweden)

    Yan Liu

    Full Text Available Accurate and automatic brain metastases target delineation is a key step for efficient and effective stereotactic radiosurgery (SRS treatment planning. In this work, we developed a deep learning convolutional neural network (CNN algorithm for segmenting brain metastases on contrast-enhanced T1-weighted magnetic resonance imaging (MRI datasets. We integrated the CNN-based algorithm into an automatic brain metastases segmentation workflow and validated on both Multimodal Brain Tumor Image Segmentation challenge (BRATS data and clinical patients' data. Validation on BRATS data yielded average DICE coefficients (DCs of 0.75±0.07 in the tumor core and 0.81±0.04 in the enhancing tumor, which outperformed most techniques in the 2015 BRATS challenge. Segmentation results of patient cases showed an average of DCs 0.67±0.03 and achieved an area under the receiver operating characteristic curve of 0.98±0.01. The developed automatic segmentation strategy surpasses current benchmark levels and offers a promising tool for SRS treatment planning for multiple brain metastases.

  19. Effective electric fields along realistic DTI-based neural trajectories for modelling the stimulation mechanisms of TMS

    NARCIS (Netherlands)

    De Geeter, N.; Crevecoeur, G.; Leemans, A.; Dupré, L.

    2015-01-01

    In transcranial magnetic stimulation (TMS), an applied alternating magnetic field induces an electric field in the brain that can interact with the neural system. It is generally assumed that this induced electric field is the crucial effect exciting a certain region of the brain. More specifically,

  20. Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain.

    Science.gov (United States)

    Albuixech-Crespo, Beatriz; López-Blanch, Laura; Burguera, Demian; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Irimia, Manuel; Ferran, José Luis

    2017-04-01

    All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.

  1. An engineered split M.HhaI-zinc finger fusion lacks the intended methyltransferase specificity

    International Nuclear Information System (INIS)

    Meister, Glenna E.; Chandrasegaran, Srinivasan; Ostermeier, Marc

    2008-01-01

    The ability to site-specifically methylate DNA in vivo would have wide applicability to the study of basic biomedical problems as well as enable studies on the potential of site-specific DNA methylation as a therapeutic strategy for the treatment of diseases. Natural DNA methyltransferases lack the specificity required for these applications. Nomura and Barbas [W. Nomura, C.F. Barbas 3rd, In vivo site-specific DNA methylation with a designed sequence-enabled DNA methylase, J. Am. Chem. Soc. 129 (2007) 8676-8677] have reported that an engineered DNA methyltransferase comprised of fragments of M.HhaI methyltransferase and zinc finger proteins has very high specificity for the chosen target site. Our analysis of this engineered enzyme shows that the fusion protein methylates target and non-target sites with similar efficiency

  2. PLZF regulates fibroblast growth factor responsiveness and maintenance of neural progenitors.

    Science.gov (United States)

    Gaber, Zachary B; Butler, Samantha J; Novitch, Bennett G

    2013-10-01

    Distinct classes of neurons and glial cells in the developing spinal cord arise at specific times and in specific quantities from spatially discrete neural progenitor domains. Thus, adjacent domains can exhibit marked differences in their proliferative potential and timing of differentiation. However, remarkably little is known about the mechanisms that account for this regional control. Here, we show that the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF) plays a critical role shaping patterns of neuronal differentiation by gating the expression of Fibroblast Growth Factor (FGF) Receptor 3 and responsiveness of progenitors to FGFs. PLZF elevation increases FGFR3 expression and STAT3 pathway activity, suppresses neurogenesis, and biases progenitors towards glial cell production. In contrast, PLZF loss reduces FGFR3 levels, leading to premature neuronal differentiation. Together, these findings reveal a novel transcriptional strategy for spatially tuning the responsiveness of distinct neural progenitor groups to broadly distributed mitogenic signals in the embryonic environment.

  3. Neural signatures of social conformity: A coordinate-based activation likelihood estimation meta-analysis of functional brain imaging studies.

    Science.gov (United States)

    Wu, Haiyan; Luo, Yi; Feng, Chunliang

    2016-12-01

    People often align their behaviors with group opinions, known as social conformity. Many neuroscience studies have explored the neuropsychological mechanisms underlying social conformity. Here we employed a coordinate-based meta-analysis on neuroimaging studies of social conformity with the purpose to reveal the convergence of the underlying neural architecture. We identified a convergence of reported activation foci in regions associated with normative decision-making, including ventral striatum (VS), dorsal posterior medial frontal cortex (dorsal pMFC), and anterior insula (AI). Specifically, consistent deactivation of VS and activation of dorsal pMFC and AI are identified when people's responses deviate from group opinions. In addition, the deviation-related responses in dorsal pMFC predict people's conforming behavioral adjustments. These are consistent with current models that disagreement with others might evoke "error" signals, cognitive imbalance, and/or aversive feelings, which are plausibly detected in these brain regions as control signals to facilitate subsequent conforming behaviors. Finally, group opinions result in altered neural correlates of valuation, manifested as stronger responses of VS to stimuli endorsed than disliked by others. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. EEG classification of emotions using emotion-specific brain functional network.

    Science.gov (United States)

    Gonuguntla, V; Shafiq, G; Wang, Y; Veluvolu, K C

    2015-08-01

    The brain functional network perspective forms the basis to relate mechanisms of brain functions. This work analyzes the network mechanisms related to human emotion based on synchronization measure - phase-locking value in EEG to formulate the emotion specific brain functional network. Based on network dissimilarities between emotion and rest tasks, most reactive channel pairs and the reactive band corresponding to emotions are identified. With the identified most reactive pairs, the subject-specific functional network is formed. The identified subject-specific and emotion-specific dynamic network pattern show significant synchrony variation in line with the experiment protocol. The same network pattern are then employed for classification of emotions. With the study conducted on the 4 subjects, an average classification accuracy of 62 % was obtained with the proposed technique.

  5. Common and metal-specific proteomic responses to cadmium and zinc in the metal tolerant ericoid mycorrhizal fungus Oidiodendron maius Zn.

    Science.gov (United States)

    Chiapello, M; Martino, E; Perotto, S

    2015-05-01

    Although adaptive metal tolerance may arise in fungal populations in polluted soils, the mechanisms underlying metal-specific tolerance are poorly understood. Comparative proteomics is a powerful tool to identify variation in protein profiles caused by changing environmental conditions, and was used to investigate protein accumulation in a metal tolerant isolate of the ericoid mycorrhizal fungus Oidiodendron maius exposed to zinc and cadmium. Two-dimensional gel electrophoresis and shotgun proteomics followed by mass spectrometry lead to the identification of common and metal-specific proteins and pathways. Proteins selectively induced by cadmium exposure were molecular chaperons of the Hsp90 family, cytoskeletal proteins and components of the translation machinery. Zinc significantly up-regulated metabolic pathways related to energy production and carbohydrates metabolism, likely mirroring zinc adaptation of this fungal isolate. Common proteins induced by the two metal ions were the antioxidant enzyme Cu/Zn superoxide dismutase and ubiquitin. In mycelia exposed to zinc and cadmium, both proteomic techniques also identified agmatinase, an enzyme involved in polyamine biosynthesis. This novel finding suggests that, like plants, polyamines may have important functions in response to abiotic environmental stress in fungi. Genetic evidence also suggests that the biosynthesis of polyamines via an alternative metabolic pathway may be widespread in fungi.

  6. Conscious access is linked to ongoing brain state: electrophysiological evidence from the attentional blink.

    Science.gov (United States)

    Pincham, Hannah L; Szucs, Dénes

    2012-10-01

    Neuroscience explanations of conscious access focus on neural events elicited by stimuli. In contrast, here, we used the attentional blink paradigm in combination with event-related brain potentials to examine whether the ongoing state of the brain before a stimulus can determine both conscious access and the poststimulus neural events associated with consciousness. Participants were required to detect 2 target letters from digit distractors while their brain activity was being recorded. Trials were classified based on whether the secondcritical target (T2) was detected. We found that T2-detection was predetermined by brain activity prior to the onset of the stimulation stream. Specifically, T2-detected trials were predicated by a frontocentral positive going deflection that started more than 200 ms before the stream began. Accurate T2 detection was also accompanied by enhanced poststimulus neural activity, as reflected by a larger P3b component. Furthermore, prestimulus and poststimulus markers of T2-detection were highly correlated with one another. We therefore argue that conscious experiences are shaped by potentially random fluctuations in neural activity. Overall, the results reveal that conscious access is underpinned by an important relationship involving predictive prestimulus neural activity and responsive poststimulus brain activity.

  7. Regulated expression of the neural cell adhesion molecule L1 by specific patterns of neural impulses.

    Science.gov (United States)

    Itoh, K; Stevens, B; Schachner, M; Fields, R D

    1995-11-24

    Development of the mammalian nervous system is regulated by neural impulse activity, but the molecular mechanisms are not well understood. If cell recognition molecules [for example, L1 and the neural cell adhesion molecule (NCAM)] were influenced by specific patterns of impulse activity, cell-cell interactions controlling nervous system structure could be regulated by nervous system function at critical stages of development. Low-frequency electrical pulses delivered to mouse sensory neurons in culture (0.1 hertz for 5 days) down-regulated expression of L1 messenger RNA and protein (but not NCAM). Fasciculation of neurites, adhesion of neuroblastoma cells, and the number of Schwann cells on neurites was reduced after 0.1-hertz stimulation, but higher frequencies or stimulation after synaptogenesis were without effect.

  8. MRI visualization of endogenous neural progenitor cell migration along the RMS in the adult mouse brain

    DEFF Research Database (Denmark)

    Vreys, Ruth; Vande Velde, Greetje; Krylychkina, Olga

    2010-01-01

    The adult rodent brain contains neural progenitor cells (NPCs), generated in the subventricular zone (SVZ), which migrate along the rostral migratory stream (RMS) towards the olfactory bulb (OB) where they differentiate into neurons. The aim of this study was to visualize endogenous NPC migration...... by a longitudinal MRI study and validated with histology. Here, we visualized endogenous NPC migration in the mouse brain by in vivo MRI and demonstrated accumulation of MPIO-labeled NPCs in the OB over time with ex vivo MRI. Furthermore, we investigated the influence of in situ injection of MPIOs on adult...

  9. A model of stimulus-specific neural assemblies in the insect antennal lobe.

    Directory of Open Access Journals (Sweden)

    Dominique Martinez

    2008-08-01

    Full Text Available It has been proposed that synchronized neural assemblies in the antennal lobe of insects encode the identity of olfactory stimuli. In response to an odor, some projection neurons exhibit synchronous firing, phase-locked to the oscillations of the field potential, whereas others do not. Experimental data indicate that neural synchronization and field oscillations are induced by fast GABA(A-type inhibition, but it remains unclear how desynchronization occurs. We hypothesize that slow inhibition plays a key role in desynchronizing projection neurons. Because synaptic noise is believed to be the dominant factor that limits neuronal reliability, we consider a computational model of the antennal lobe in which a population of oscillatory neurons interact through unreliable GABA(A and GABA(B inhibitory synapses. From theoretical analysis and extensive computer simulations, we show that transmission failures at slow GABA(B synapses make the neural response unpredictable. Depending on the balance between GABA(A and GABA(B inputs, particular neurons may either synchronize or desynchronize. These findings suggest a wiring scheme that triggers stimulus-specific synchronized assemblies. Inhibitory connections are set by Hebbian learning and selectively activated by stimulus patterns to form a spiking associative memory whose storage capacity is comparable to that of classical binary-coded models. We conclude that fast inhibition acts in concert with slow inhibition to reformat the glomerular input into odor-specific synchronized neural assemblies.

  10. Specific diagnosis of brain disease with double isotope brain scanning

    Energy Technology Data Exchange (ETDEWEB)

    Ell, P J; Lotritsch, K H; Hilbrand, E; Meixner, M; Barolin, G; Scholz, H [Landesunfallkrankenhaus, Feldkirch (Austria). Dept. of Nuclear Medicine; Landesnervenkrankenhaus, Feldkirch (Austria). Dept. of Neurology)

    1976-02-01

    25 patients with known cerebral disease (either CVA's or primary or secondary tumours) diagnosed by clinical and angiographic criteria were submitted to a double siotope imaging technique using sup(99m)TcO/sub 4/- and sup(99m)Tc-EHDP. The different biological behaviour of these radiopharmaceuticals has provided specific and differential diagnosis between vascular and neoplastic disease of the brain. sup(99m)Tc-EHDP is shown to be the tracer of choice for the imaging of CVA's and sup(99m)TcO/sub 4/- is confirmed as the tracer of choice for the imaging of primary or secondary tumours in the brain.

  11. Relation of visual creative imagery manipulation to resting-state brain oscillations.

    Science.gov (United States)

    Cai, Yuxuan; Zhang, Delong; Liang, Bishan; Wang, Zengjian; Li, Junchao; Gao, Zhenni; Gao, Mengxia; Chang, Song; Jiao, Bingqing; Huang, Ruiwang; Liu, Ming

    2018-02-01

    Visual creative imagery (VCI) manipulation is the key component of visual creativity; however, it remains largely unclear how it occurs in the brain. The present study investigated the brain neural response to VCI manipulation and its relation to intrinsic brain activity. We collected functional magnetic resonance imaging (fMRI) datasets related to a VCI task and a control task as well as pre- and post-task resting states in sequential sessions. A general linear model (GLM) was subsequently used to assess the specific activation of the VCI task compared with the control task. The changes in brain oscillation amplitudes across the pre-, on-, and post-task states were measured to investigate the modulation of the VCI task. Furthermore, we applied a Granger causal analysis (GCA) to demonstrate the dynamic neural interactions that underlie the modulation effect. We determined that the VCI task specifically activated the left inferior frontal gyrus pars triangularis (IFGtriang) and the right superior frontal gyrus (SFG), as well as the temporoparietal areas, including the left inferior temporal gyrus, right precuneus, and bilateral superior parietal gyrus. Furthermore, the VCI task modulated the intrinsic brain activity of the right IFGtriang (0.01-0.08 Hz) and the left caudate nucleus (0.2-0.25 Hz). Importantly, an inhibitory effect (negative) may exist from the left SFG to the right IFGtriang in the on-VCI task state, in the frequency of 0.01-0.08 Hz, whereas this effect shifted to an excitatory effect (positive) in the subsequent post-task resting state. Taken together, the present findings provide experimental evidence for the existence of a common mechanism that governs the brain activity of many regions at resting state and whose neural activity may engage during the VCI manipulation task, which may facilitate an understanding of the neural substrate of visual creativity.

  12. Deep-brain electrical microstimulation is an effective tool to explore functional characteristics of somatosensory neurons in the rat brain.

    Directory of Open Access Journals (Sweden)

    Han-Jia Jiang

    Full Text Available In neurophysiology researches, peripheral stimulation is used along with recordings of neural activities to study the processing of somatosensory signals in the brain. However, limited precision of peripheral stimulation makes it difficult to activate the neuron with millisecond resolution and study its functional properties in this scale. Also, tissue/receptor damage that could occur in some experiments often limits the amount of responses that can be recorded and hence reduces data reproducibility. To overcome these limitations, electrical microstimulation (ES of the brain could be used to directly and more precisely evoke neural responses. For this purpose, a deep-brain ES protocol for rat somatosensory relay neurons was developed in this study. Three male Wistar rats were used in the experiment. The ES was applied to the thalamic region responsive to hindpaw tactile stimulation (TS via a theta glass microelectrode. The resulting ES-evoked cortical responses showed action potentials and thalamocortical relay latencies very similar to those evoked by TS. This result shows that the developed deep-brain ES protocol is an effective tool to bypass peripheral tissue for in vivo functional analysis of specific types of somatosensory neurons. This protocol could be readily applied in researches of nociception and other somatosensory systems to allow more extensive exploration of the neural functional networks.

  13. [Synergistic application of zinc and vitamin C to support memory, attention and the reduction of the risk of the neurological diseases].

    Science.gov (United States)

    Gromova, O A; Torshin, I Yu; Pronin, A V; Kilchevsky, M A

    Zinc and vitamin C supplementation of the body is important for CNS functioning. Zinc ions are involved in the neurotransmission (signal transmission from acetylcholine, catecholamine, serotonin, prostaglandin receptors) and in ubiquitin-related protein degradation. Zinc deficits are associated with Alzheimer's disease and depression. Zinc supplementation (10-30 mg daily) improves neurologic recovery rate in patients with stroke and brain injury, has a positive impact on memory and reduces hyperactivity in children. Vitamin C, a zinc synergist, maintains antioxidant resources of the brain, synaptic activity and detoxification. Vitamin C in dose 130-500 mg daily should be used to prevent dementia and neurodegenerative pathology.

  14. Zinc Binding by Lactic Acid Bacteria

    Directory of Open Access Journals (Sweden)

    Jasna Mrvčić

    2009-01-01

    Full Text Available Zinc is an essential trace element in all organisms. A common method for the prevention of zinc deficiency is pharmacological supplementation, especially in a highly available form of a metalloprotein complex. The potential of different microbes to bind essential and toxic heavy metals has recently been recognized. In this work, biosorption of zinc by lactic acid bacteria (LAB has been investigated. Specific LAB were assessed for their ability to bind zinc from a water solution. Significant amount of zinc ions was bound, and this binding was found to be LAB species-specific. Differences among the species in binding performance at a concentration range between 10–90 mg/L were evaluated with Langmuir model for biosorption. Binding of zinc was a fast process, strongly influenced by ionic strength, pH, biomass concentration, and temperature. The most effective metal-binding LAB species was Leuconostoc mesenteroides (27.10 mg of Zn2+ per gram of dry mass bound at pH=5 and 32 °C, during 24 h. FT-IR spectroscopy analysis and electron microscopy demonstrated that passive adsorption and active uptake of the zinc ions were involved.

  15. Chloroquine is a zinc ionophore.

    Directory of Open Access Journals (Sweden)

    Jing Xue

    Full Text Available Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780. Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.

  16. Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses.

    Science.gov (United States)

    Yan, Yuanwei; Bejoy, Julie; Xia, Junfei; Guan, Jingjiao; Zhou, Yi; Li, Yan

    2016-09-15

    Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells/tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capacity of signaling factors that regulate 3-D neural tissue patterning in vitro and differential responses of the resulting neural populations to various biomolecules have not yet been fully understood. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog (SHH) signaling, this study generated different 3-D neuronal cultures that were mainly comprised of either cortical glutamatergic neurons or motor neurons. Abundant glutamatergic neurons were observed following the treatment with an antagonist of SHH signaling, cyclopamine, while Islet-1 and HB9-expressing motor neurons were enriched by an SHH agonist, purmorphamine. In neurons derived with different neural patterning factors, whole-cell patch clamp recordings showed similar voltage-gated Na(+)/K(+) currents, depolarization-evoked action potentials and spontaneous excitatory post-synaptic currents. Moreover, these different neuronal populations exhibited differential responses to three classes of biomolecules, including (1) matrix metalloproteinase inhibitors that affect extracellular matrix remodeling; (2) N-methyl-d-aspartate that induces general neurotoxicity; and (3) amyloid β (1-42) oligomers that cause neuronal subtype-specific neurotoxicity. This study should advance our understanding of hiPSC self-organization and neural tissue development and provide a transformative approach to establish 3-D models for neurological disease modeling and drug discovery. Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells, tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capability of sonic hedgehog-related small molecules to tune

  17. A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback.

    Directory of Open Access Journals (Sweden)

    Christopher L Buckley

    2018-01-01

    Full Text Available During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results

  18. A theory of how active behavior stabilises neural activity: Neural gain modulation by closed-loop environmental feedback.

    Science.gov (United States)

    Buckley, Christopher L; Toyoizumi, Taro

    2018-01-01

    During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input. We support this theory with modeling and data analysis in two vertebrate systems. First, in a model of rodent whisking we show that negative feedback mediated by whisking vibrissa can suppress coherent neural fluctuations and neural responses to sensory input in the barrel cortex. We argue this suppression provides an appealing account of a brain state transition (a marked change in global brain activity) coincident with the onset of whisking in rodents. Moreover, this mechanism suggests a novel signal detection mechanism that selectively accentuates active, rather than passive, whisker touch signals. This mechanism is consistent with a predictive coding strategy that is sensitive to the consequences of motor actions rather than the difference between the predicted and actual sensory input. We further support the theory by re-analysing previously published two-photon data recorded in zebrafish larvae performing closed-loop optomotor behaviour in a virtual swim simulator. We show, as predicted by this theory, that the degree to which each cell contributes in linking sensory and motor signals well explains how much its neural fluctuations are suppressed by closed-loop optomotor behaviour. More generally we argue that our results demonstrate the dependence

  19. Development of the Adolescent Brain: Implications for Executive Function and Social Cognition

    Science.gov (United States)

    Blakemore, Sarah-Jayne; Choudhury, Suparna

    2006-01-01

    Adolescence is a time of considerable development at the level of behaviour, cognition and the brain. This article reviews histological and brain imaging studies that have demonstrated specific changes in neural architecture during puberty and adolescence, outlining trajectories of grey and white matter development. The implications of brain…

  20. Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs.

    Science.gov (United States)

    Kutejova, Eva; Sasai, Noriaki; Shah, Ankita; Gouti, Mina; Briscoe, James

    2016-03-21

    In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. 21 CFR 558.78 - Bacitracin zinc.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Bacitracin zinc. 558.78 Section 558.78 Food and... in Animal Feeds § 558.78 Bacitracin zinc. (a) Specifications. Type A medicated articles containing bacitracin zinc equivalent to 10, 25, 40, or 50 grams per pound bacitracin. (b) Approvals. See No. 046573 in...

  2. Brain Region-Dependent Rejection of Neural Precursor Cell Transplants

    Directory of Open Access Journals (Sweden)

    Nina Fainstein

    2018-04-01

    Full Text Available The concept of CNS as an immune-privileged site has been challenged by the occurrence of immune surveillance and allogeneic graft rejection in the brain. Here we examined whether the immune response to allogeneic neural grafts is determined by the site of implantation in the CNS. Dramatic regional differences were observed between immune responses to allogeneic neural precursor/stem cell (NPC grafts in the striatum vs. the hippocampus. Striatal grafts were heavily infiltrated with IBA-1+ microglia/macrophages and CD3+ T cells and completely rejected. In contrast, hippocampal grafts exhibited milder IBA-1+ cell infiltration, were not penetrated efficiently by CD3+ cells, and survived efficiently for at least 2 months. To evaluate whether the hippocampal protective effect is universal, astrocytes were then transplanted. Allogeneic astrocyte grafts elicited a vigorous rejection process from the hippocampus. CD200, a major immune-inhibitory signal, plays an important role in protecting grafts from rejection. Indeed, CD200 knock out NPC grafts were rejected more efficiently than wild type NPCs from the striatum. However, lack of CD200 expression did not elicit NPC graft rejection from the hippocampus. In conclusion, the hippocampus has partial immune-privilege properties that are restricted to NPCs and are CD200-independent. The unique hippocampal milieu may be protective for allogeneic NPC grafts, through host-graft interactions enabling sustained immune-regulatory properties of transplanted NPCs. These findings have implications for providing adequate immunosuppression in clinical translation of cell therapy.

  3. The Neural Mechanisms of Re-Experiencing Mental Fatigue Sensation: A Magnetoencephalography Study

    OpenAIRE

    Ishii, Akira; Karasuyama, Takuma; Kikuchi, Taiki; Tanaka, Masaaki; Yamano, Emi; Watanabe, Yasuyoshi

    2015-01-01

    There have been several studies which have tried to clarify the neural mechanisms of fatigue sensation; however fatigue sensation has multiple aspects. We hypothesized that past experience related to fatigue sensation is an important factor which contributes to future formation of fatigue sensation through the transfer to memories that are located within specific brain structures. Therefore, we aimed to investigate the neural mechanisms of fatigue sensation related to memory. In the present s...

  4. Transformed Neural Pattern Reinstatement during Episodic Memory Retrieval.

    Science.gov (United States)

    Xiao, Xiaoqian; Dong, Qi; Gao, Jiahong; Men, Weiwei; Poldrack, Russell A; Xue, Gui

    2017-03-15

    Contemporary models of episodic memory posit that remembering involves the reenactment of encoding processes. Although encoding-retrieval similarity has been consistently reported and linked to memory success, the nature of neural pattern reinstatement is poorly understood. Using high-resolution fMRI on human subjects, our results obtained clear evidence for item-specific pattern reinstatement in the frontoparietal cortex, even when the encoding-retrieval pairs shared no perceptual similarity. No item-specific pattern reinstatement was found in the ventral visual cortex. Importantly, the brain regions and voxels carrying item-specific representation differed significantly between encoding and retrieval, and the item specificity for encoding-retrieval similarity was smaller than that for encoding or retrieval, suggesting different nature of representations between encoding and retrieval. Moreover, cross-region representational similarity analysis suggests that the encoded representation in the ventral visual cortex was reinstated in the frontoparietal cortex during retrieval. Together, these results suggest that, in addition to reinstatement of the originally encoded pattern in the brain regions that perform encoding processes, retrieval may also involve the reinstatement of a transformed representation of the encoded information. These results emphasize the constructive nature of memory retrieval that helps to serve important adaptive functions. SIGNIFICANCE STATEMENT Episodic memory enables humans to vividly reexperience past events, yet how this is achieved at the neural level is barely understood. A long-standing hypothesis posits that memory retrieval involves the faithful reinstatement of encoding-related activity. We tested this hypothesis by comparing the neural representations during encoding and retrieval. We found strong pattern reinstatement in the frontoparietal cortex, but not in the ventral visual cortex, that represents visual details. Critically

  5. Imaging the neural circuitry and chemical control of aggressive motivation

    Directory of Open Access Journals (Sweden)

    Blanchard D Caroline

    2008-11-01

    Full Text Available Abstract Background With the advent of functional magnetic resonance imaging (fMRI in awake animals it is possible to resolve patterns of neuronal activity across the entire brain with high spatial and temporal resolution. Synchronized changes in neuronal activity across multiple brain areas can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviors. To this end, fMRI in conscious rats combined with 3D computational analysis was used to identifying the putative distributed neural circuit involved in aggressive motivation and how this circuit is affected by drugs that block aggressive behavior. Results To trigger aggressive motivation, male rats were presented with their female cage mate plus a novel male intruder in the bore of the magnet during image acquisition. As expected, brain areas previously identified as critical in the organization and expression of aggressive behavior were activated, e.g., lateral hypothalamus, medial basal amygdala. Unexpected was the intense activation of the forebrain cortex and anterior thalamic nuclei. Oral administration of a selective vasopressin V1a receptor antagonist SRX251 or the selective serotonin reuptake inhibitor fluoxetine, drugs that block aggressive behavior, both caused a general suppression of the distributed neural circuit involved in aggressive motivation. However, the effect of SRX251, but not fluoxetine, was specific to aggression as brain activation in response to a novel sexually receptive female was unaffected. Conclusion The putative neural circuit of aggressive motivation identified with fMRI includes neural substrates contributing to emotional expression (i.e. cortical and medial amygdala, BNST, lateral hypothalamus, emotional experience (i.e. hippocampus, forebrain cortex, anterior cingulate, retrosplenial cortex and the anterior thalamic nuclei that bridge the motor and cognitive components of aggressive responding

  6. Bioavailability of zinc from sweet potato roots and leaves

    International Nuclear Information System (INIS)

    Baiden, H.N.; Ercanli-Huffman, F.G.

    1986-01-01

    Bioavailability of zinc from sweet potato (SP) roots and leaves were determined, by extrinsic labeling technique, in rats fed control and zinc deficient diets. Weanling male Sprague Dawley (SD) rats (60-75g) were divided into 4 groups, and fed laboratory chow, a control diet (ad libitum and pair fed) and a zinc deficient diet, for 4 weeks. Each group then was divided into at least 2 sub groups, containing 6 rats, which were intubated with one of 3 tubing solutions extrinsically labeled with 65 Zn; baked sweet potato roots (BSPR), raw sweet potato leaves (RSPL) and cooked sweet potato leaves (CSPL). Five hours after intubation the rats were sacrificed, blood, liver, testes, spleen, heart, brain, thymus and lungs were removed. Feces, urine, and GI tract contents were collected and their 65 Zn activity was determined in a gamma counter. In all treatment groups zinc bioavailability from BSPR, RSPL or CSPL were not significantly different. Zinc deficient rats absorbed significantly more (P 65 Zn (86-90% of the dose), regardless of type of tubing solution than the pairfed or control animals (35-58% of the dose). The highest retention of 65 Zn was found in the liver (12-20% of absorbed dose), GI tract (6-17% of absorbed dose), kidney (2-8% of absorbed dose), and blood (1-5% of absorbed dose). The lowest retention was found in the brain, heart, thymus and testes. (< 1% of absorbed dose)

  7. The Racer’s Brain – How Domain Expertise is Reflected in the Neural Substrates of Driving

    Directory of Open Access Journals (Sweden)

    Otto eLappi

    2015-11-01

    Full Text Available A fundamental question in human brain plasticity is how sensory, motor, and cognitive functions adapt in the process of skill acquisition extended over a period of many years. Recently, there has emerged a growing interest in cognitive neuroscience on studying the functional and structural differences in the brains of elite athletes. Elite performance in sports, music or the arts, allows us to observe sensorimotor and cognitive performance at the limits of human capability. In this mini-review we look at driving expertise. The emerging brain imaging literature on the neural substrates of real and simulated driving is reviewed (for the first time, and used as the context for interpreting recent findings on the differences between racing drivers and non-athlete controls. Also the cognitive psychology and cognitive neuroscience of expertise are discussed.

  8. Cell-specific gain modulation by synaptically released zinc in cortical circuits of audition.

    Science.gov (United States)

    Anderson, Charles T; Kumar, Manoj; Xiong, Shanshan; Tzounopoulos, Thanos

    2017-09-09

    In many excitatory synapses, mobile zinc is found within glutamatergic vesicles and is coreleased with glutamate. Ex vivo studies established that synaptically released (synaptic) zinc inhibits excitatory neurotransmission at lower frequencies of synaptic activity but enhances steady state synaptic responses during higher frequencies of activity. However, it remains unknown how synaptic zinc affects neuronal processing in vivo. Here, we imaged the sound-evoked neuronal activity of the primary auditory cortex in awake mice. We discovered that synaptic zinc enhanced the gain of sound-evoked responses in CaMKII-expressing principal neurons, but it reduced the gain of parvalbumin- and somatostatin-expressing interneurons. This modulation was sound intensity-dependent and, in part, NMDA receptor-independent. By establishing a previously unknown link between synaptic zinc and gain control of auditory cortical processing, our findings advance understanding about cortical synaptic mechanisms and create a new framework for approaching and interpreting the role of the auditory cortex in sound processing.

  9. Psychoanalysis and the brain - why did freud abandon neuroscience?

    Science.gov (United States)

    Northoff, Georg

    2012-01-01

    Sigmund Freud, the founder of psychoanalysis, was initially a neuroscientist but abandoned neuroscience completely after he made a last attempt to link both in his writing, "Project of a Scientific Psychology," in 1895. The reasons for his subsequent disregard of the brain remain unclear though. I here argue that one central reason may be that the approach to the brain during his time was simply not appealing to Freud. More specifically, Freud was interested in revealing the psychological predispositions of psychodynamic processes. However, he was not so much focused on the actual psychological functions themselves which though were the prime focus of the neuroscience at his time and also in current Cognitive Neuroscience. Instead, he probably would have been more interested in the brain's resting state and its constitution of a spatiotemporal structure. I here assume that the resting state activity constitutes a statistically based virtual structure extending and linking the different discrete points in time and space within the brain. That in turn may serve as template, schemata, or grid for all subsequent neural processing during stimulus-induced activity. As such the resting state' spatiotemporal structure may serve as the neural predisposition of what Freud described as "psychological structure." Hence, Freud and also current neuropsychoanalysis may want to focus more on neural predispositions, the necessary non-sufficient conditions, rather than the neural correlates, i.e., sufficient, conditions of psychodynamic processes.

  10. Artificial Astrocytes Improve Neural Network Performance

    Science.gov (United States)

    Porto-Pazos, Ana B.; Veiguela, Noha; Mesejo, Pablo; Navarrete, Marta; Alvarellos, Alberto; Ibáñez, Oscar; Pazos, Alejandro; Araque, Alfonso

    2011-01-01

    Compelling evidence indicates the existence of bidirectional communication between astrocytes and neurons. Astrocytes, a type of glial cells classically considered to be passive supportive cells, have been recently demonstrated to be actively involved in the processing and regulation of synaptic information, suggesting that brain function arises from the activity of neuron-glia networks. However, the actual impact of astrocytes in neural network function is largely unknown and its application in artificial intelligence remains untested. We have investigated the consequences of including artificial astrocytes, which present the biologically defined properties involved in astrocyte-neuron communication, on artificial neural network performance. Using connectionist systems and evolutionary algorithms, we have compared the performance of artificial neural networks (NN) and artificial neuron-glia networks (NGN) to solve classification problems. We show that the degree of success of NGN is superior to NN. Analysis of performances of NN with different number of neurons or different architectures indicate that the effects of NGN cannot be accounted for an increased number of network elements, but rather they are specifically due to astrocytes. Furthermore, the relative efficacy of NGN vs. NN increases as the complexity of the network increases. These results indicate that artificial astrocytes improve neural network performance, and established the concept of Artificial Neuron-Glia Networks, which represents a novel concept in Artificial Intelligence with implications in computational science as well as in the understanding of brain function. PMID:21526157

  11. Artificial astrocytes improve neural network performance.

    Directory of Open Access Journals (Sweden)

    Ana B Porto-Pazos

    Full Text Available Compelling evidence indicates the existence of bidirectional communication between astrocytes and neurons. Astrocytes, a type of glial cells classically considered to be passive supportive cells, have been recently demonstrated to be actively involved in the processing and regulation of synaptic information, suggesting that brain function arises from the activity of neuron-glia networks. However, the actual impact of astrocytes in neural network function is largely unknown and its application in artificial intelligence remains untested. We have investigated the consequences of including artificial astrocytes, which present the biologically defined properties involved in astrocyte-neuron communication, on artificial neural network performance. Using connectionist systems and evolutionary algorithms, we have compared the performance of artificial neural networks (NN and artificial neuron-glia networks (NGN to solve classification problems. We show that the degree of success of NGN is superior to NN. Analysis of performances of NN with different number of neurons or different architectures indicate that the effects of NGN cannot be accounted for an increased number of network elements, but rather they are specifically due to astrocytes. Furthermore, the relative efficacy of NGN vs. NN increases as the complexity of the network increases. These results indicate that artificial astrocytes improve neural network performance, and established the concept of Artificial Neuron-Glia Networks, which represents a novel concept in Artificial Intelligence with implications in computational science as well as in the understanding of brain function.

  12. Artificial astrocytes improve neural network performance.

    Science.gov (United States)

    Porto-Pazos, Ana B; Veiguela, Noha; Mesejo, Pablo; Navarrete, Marta; Alvarellos, Alberto; Ibáñez, Oscar; Pazos, Alejandro; Araque, Alfonso

    2011-04-19

    Compelling evidence indicates the existence of bidirectional communication between astrocytes and neurons. Astrocytes, a type of glial cells classically considered to be passive supportive cells, have been recently demonstrated to be actively involved in the processing and regulation of synaptic information, suggesting that brain function arises from the activity of neuron-glia networks. However, the actual impact of astrocytes in neural network function is largely unknown and its application in artificial intelligence remains untested. We have investigated the consequences of including artificial astrocytes, which present the biologically defined properties involved in astrocyte-neuron communication, on artificial neural network performance. Using connectionist systems and evolutionary algorithms, we have compared the performance of artificial neural networks (NN) and artificial neuron-glia networks (NGN) to solve classification problems. We show that the degree of success of NGN is superior to NN. Analysis of performances of NN with different number of neurons or different architectures indicate that the effects of NGN cannot be accounted for an increased number of network elements, but rather they are specifically due to astrocytes. Furthermore, the relative efficacy of NGN vs. NN increases as the complexity of the network increases. These results indicate that artificial astrocytes improve neural network performance, and established the concept of Artificial Neuron-Glia Networks, which represents a novel concept in Artificial Intelligence with implications in computational science as well as in the understanding of brain function.

  13. Zinc release in the lateral nucleus of the amygdala by stimulation of the entorhinal cortex.

    Science.gov (United States)

    Takeda, Atsushi; Imano, Sachie; Itoh, Hiromasa; Oku, Naoto

    2006-11-06

    Zinc release in the lateral nucleus of the amygdala was examined using rat brain slices. The lateral and basolateral nuclei in the amygdala were evidently stained by Timm's sulfide-silver staining method. When the amygdala including both the nuclei was stimulated with 100 mM KCl by means of in vivo microdialysis, extracellular zinc concentration was increased significantly. Zinc release in the lateral nucleus of the amygdala innervated by the entorhinal cortex was next examined in brain slices double-stained with zinc and calcium indicators. Extracellular zinc signal (ZnAF-2) in the lateral nucleus was increased with intracellular calcium signal (calcium orange) during delivery of tetanic stimuli to the entorhinal cortex. Both the increases were completely inhibited by addition of 1 micro M tetrodotoxin, a sodium channel blocker. Furthermore, calcium signal in the lateral nucleus during delivery of tetanic stimuli to the entorhinal cortex was increased in the presence of 10 micro M CNQX, an AMPA/KA receptor antagonist, and this increase was facilitated by addition of 1 mM CaEDTA, a membrane-impermeable zinc chelator. The present study suggested that zinc is released in the lateral nucleus of the amygdala by depolarization of the entorhinal neurons. In the lateral nucleus, zinc released may suppress the increase in presynaptic calcium signal.

  14. Long-Term Effects of Ketogenic Diet on Subsequent Seizure-Induced Brain Injury During Early Adulthood: Relationship of Seizure Thresholds to Zinc Transporter-Related Gene Expressions.

    Science.gov (United States)

    Tian, Tian; Li, Li-Li; Zhang, Shu-Qi; Ni, Hong

    2016-12-01

    The divalent cation zinc is associated with cortical plasticity. However, the mechanism of zinc in the pathophysiology of cortical injury-associated neurobehavioral damage following neonatal seizures is uncertain. We have previously shown upregulated expression of ZnT-3; MT-3 in hippocampus of neonatal rats submitted to flurothyl-induced recurrent seizures, which was restored by pretreatment with ketogenic diet (KD). In this study, utilizing a novel "twist" seizure model by coupling early-life flurothyl-induced seizures with later exposure to penicillin, we further investigated the long-term effects of KD on cortical expression of zinc homeostasis-related genes in a systemic scale. Ten Sprague-Dawley rats were assigned each averagely into the non-seizure plus normal diet (NS + ND), non-seizure plus KD (NS + KD), recurrent seizures plus normal diet (RS + ND) and recurrent seizures plus KD (RS + KD) group. Recurrent seizures were induced by volatile flurothyl during P9-P21. During P23-P53, rats in NS + KD and RS + KD groups were dieted with KD. Neurological behavioral parameters of brain damage (plane righting reflex, cliff avoidance reflex, and open field test) were observed at P43. At P63, we examined seizure threshold using penicillin, then the cerebral cortex were evaluated for real-time RT-PCR and western blot study. The RS + ND group showed worse performances in neurological reflex tests and reduced latencies to myoclonic seizures induced by penicillin compared with the control, which was concomitant with altered expressions of ZnT-7, MT-1, MT-2, and ZIP7. Specifically, there was long-term elevated expression of ZIP7 in RS + ND group compared with that in NS + ND that was restored by chronic ketogenic diet (KD) treatment in RS + KD group, which was quite in parallel with the above neurobehavioral changes. Taken together, these findings indicate that the long-term altered expression of the metal transporter ZIP7 in adult cerebral cortex might

  15. Automatic detection and segmentation of brain metastases on multimodal MR images with a deep convolutional neural network.

    Science.gov (United States)

    Charron, Odelin; Lallement, Alex; Jarnet, Delphine; Noblet, Vincent; Clavier, Jean-Baptiste; Meyer, Philippe

    2018-04-01

    Stereotactic treatments are today the reference techniques for the irradiation of brain metastases in radiotherapy. The dose per fraction is very high, and delivered in small volumes (diameter convolutional neural network (DeepMedic) to detect and segment brain metastases on MRI. At first, we sought to adapt the network parameters to brain metastases. We then explored the single or combined use of different MRI modalities, by evaluating network performance in terms of detection and segmentation. We also studied the interest of increasing the database with virtual patients or of using an additional database in which the active parts of the metastases are separated from the necrotic parts. Our results indicated that a deep network approach is promising for the detection and the segmentation of brain metastases on multimodal MRI. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Zinc fingers, zinc clusters, and zinc twists in DNA-binding protein domains

    International Nuclear Information System (INIS)

    Vallee, B.L.; Auld, D.S.; Coleman, J.E.

    1991-01-01

    The authors recognize three distinct motifs of DNA-binding zinc proteins: (i) zinc fingers, (ii) zinc clusters, and (iii) zinc twists. Until very recently, x-ray crystallographic or NMR three-dimensional structure analyses of DNA-binding zinc proteins have not been available to serve as standards of reference for the zinc binding sites of these families of proteins. Those of the DNA-binding domains of the fungal transcription factor GAL4 and the rat glucocorticoid receptor are the first to have been determined. Both proteins contain two zinc binding sites, and in both, cysteine residues are the sole zinc ligands. In GAL4, two zinc atoms are bound to six cysteine residues which form a zinc cluster akin to that of metallothionein; the distance between the two zinc atoms of GAL4 is ∼3.5 angstrom. In the glucocorticoid receptor, each zinc atom is bound to four cysteine residues; the interatomic zinc-zinc distance is ∼13 angstrom, and in this instance, a zinc twist is represented by a helical DNA recognition site located between the two zinc atoms. Zinc clusters and zinc twists are here recognized as two distinctive motifs in DNA-binding proteins containing multiple zinc atoms. For native zinc fingers, structural data do not exist as yet; consequently, the interatomic distances between zinc atoms are not known. As further structural data become available, the structural and functional significance of these different motifs in their binding to DNA and other proteins participating in the transmission of the genetic message will become apparent

  17. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin

    2017-01-01

    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...... for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various...

  18. The neural basis of body form and body action agnosia.

    Science.gov (United States)

    Moro, Valentina; Urgesi, Cosimo; Pernigo, Simone; Lanteri, Paola; Pazzaglia, Mariella; Aglioti, Salvatore Maria

    2008-10-23

    Visual analysis of faces and nonfacial body stimuli brings about neural activity in different cortical areas. Moreover, processing body form and body action relies on distinct neural substrates. Although brain lesion studies show specific face processing deficits, neuropsychological evidence for defective recognition of nonfacial body parts is lacking. By combining psychophysics studies with lesion-mapping techniques, we found that lesions of ventromedial, occipitotemporal areas induce face and body recognition deficits while lesions involving extrastriate body area seem causatively associated with impaired recognition of body but not of face and object stimuli. We also found that body form and body action recognition deficits can be double dissociated and are causatively associated with lesions to extrastriate body area and ventral premotor cortex, respectively. Our study reports two category-specific visual deficits, called body form and body action agnosia, and highlights their neural underpinnings.

  19. Neural overlap in processing music and speech

    Science.gov (United States)

    Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L.

    2015-01-01

    Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. PMID:25646513

  20. Penfield's prediction: a mechanism for deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Richard W. Murrow

    2014-10-01

    Full Text Available (1Context: Despite its widespread use, the precise mechanism of action of Deep Brain Stimulation (DBS therapy remains unknown. The modern urgency to publish more and new data can obscure previously learned lessons by the giants who have preceded us and whose shoulders we now stand upon. Wilder Penfield extensively studied the effects of artificial electrical brain stimulation and his comments on the subject are still very relevant today. In particular, he noted two very different (and seemingly opposite effects of stimulation within the human brain. In some structures, artificial electrical stimulation has an effect which mimics ablation, while, in other structures, it produces a stimulatory effect on that tissue. (2Hypothesis:The hypothesis of this paper is fourfold. First, it proposes that some neural circuits are widely synchronized with other neural circuits, while some neural circuits are unsynchronized and operate independently. Second, it proposes that artificial high frequency electrical stimulation of a synchronized neural circuit results in an ablative effect, but artificial high frequency electrical stimulation of an unsynchronized neural circuit results in a stimulatory effect. Third, it suggests a part of the mechanism by which large scale physiologic synchronization of widely distributed independently processed information streams may occur. This may be the neural mechanism underlying Penfield’s centrencephalic system which he emphasized so many years ago. Fourth, it outlines the specific anatomic distribution of this physiologic synchronization, which Penfield has already clearly delineated as the distribution of his centrencephalic system. (3Evidence:This paper draws on a brief overview of previous theory regarding the mechanism of action of DBS and on historical, as well as widely known modern clinical data regarding the observed effects of stimulation delivered to various targets within the brain. Basic science in

  1. Brain-Derived Neurotrophic Factor Loaded PS80 PBCA Nanocarrier for In Vitro Neural Differentiation of Mouse Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Chiu-Yen Chung

    2017-03-01

    Full Text Available Brain derived neurotrophic factor (BDNF can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC was constructed to deliver plasmid DNAs (pDNAs containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF. The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting. The HRE-cmvBDNF appeared to adsorb onto the surface of PS80 PBCA NC, with a resultant mean diameter of 92.6 ± 1.0 nm and zeta potential of −14.1 ± 1.1 mV. HIF-1α level in iPSCs was significantly higher in hypoxia, which resulted in a 51% greater BDNF expression when transfected with PS80 PBCA NC/HRE-cmvBDNF than those without hypoxia. TrkB and phospho-Akt were also elevated which correlated with neural differentiation. The findings suggest that PS80 PBCA NC too can be endocytosed to serve as an efficient vector for genes coupled to the HRE in hypoxia-sensitive cells, and activation of the PI3/Akt pathway in iPSCs by BDNF is capable of neural lineage specification.

  2. Toward the Development of an Artificial Brain on a Micropatterned and Material-Regulated Biochip by Guiding and Promoting the Differentiation and Neurite Outgrowth of Neural Stem/Progenitor Cells.

    Science.gov (United States)

    Liu, Yung-Chiang; Lee, I-Chi; Lei, Kin Fong

    2018-02-14

    An in vitro model mimicking the in vivo environment of the brain must be developed to study neural communication and regeneration and to obtain an understanding of cellular and molecular responses. In this work, a multilayered neural network was successfully constructed on a biochip by guiding and promoting neural stem/progenitor cell differentiation and network formation. The biochip consisted of 3 × 3 arrays of cultured wells connected with channels. Neurospheroids were cultured on polyelectrolyte multilayer (PEM) films in the culture wells. Neurite outgrowth and neural differentiation were guided and promoted by the micropatterns and the PEM films. After 5 days in culture, a 3 × 3 neural network was constructed on the biochip. The function and the connections of the network were evaluated by immunocytochemistry and impedance measurements. Neurons were generated and produced functional and recyclable synaptic vesicles. Moreover, the electrical connections of the neural network were confirmed by measuring the impedance across the neurospheroids. The current work facilitates the development of an artificial brain on a chip for investigations of electrical stimulations and recordings of multilayered neural communication and regeneration.

  3. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  4. Neural precursor cells in the ischemic brain - integration, cellular crosstalk and consequences for stroke recovery

    Directory of Open Access Journals (Sweden)

    Dirk M. Hermann

    2014-09-01

    Full Text Available After an ischemic stroke, neural precursor cells (NPCs proliferate within major germinal niches of the brain. Endogenous NPCs subsequently migrate towards the ischemic lesion where they promote tissue remodelling and neural repair. Unfortunately, this restorative process is generally insufficient and thus unable to support a full recovery of lost neurological functions. Supported by solid experimental and preclinical data, the transplantation of exogenous NPCs has emerged as a potential tool for stroke treatment. Transplanted NPCs are thought to act mainly via trophic and immune modulatory effects, thereby complementing the restorative responses initially executed by the endogenous NPC population. Recent studies have attempted to elucidate how the therapeutic properties of transplanted NPCs vary depending on the route of transplantation. Systemic NPC delivery leads to potent immune modulatory actions, which prevent secondary neuronal degeneration, reduces glial scar formation, diminishes oxidative stress and stabilizes blood-brain barrier integrity. On the contrary, local stem cell delivery, allows for the accumulation of large numbers of transplanted NPCs in the brain, thus achieving high levels of locally available tissue trophic factors, which may better induce a strong endogenous NPC proliferative response.Herein we describe the diverse capabilities of exogenous (systemically vs locally transplanted NPCs in enhancing the endogenous neurogenic response after stroke, and how the route of transplantation may affect migration, survival, bystander effects and integration of the cellular graft. It is the authors’ claim that understanding these aspects will be of pivotal importance in discerning how transplanted NPCs exert their therapeutic effects in stroke.

  5. Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen

    Directory of Open Access Journals (Sweden)

    Anna Benedykcinska

    2016-02-01

    Full Text Available Targeted cell- or region-specific gene recombination is widely used in the functional analysis of genes implicated in development and disease. In the brain, targeted gene recombination has become a mainstream approach to study neurodegeneration or tumorigenesis. The use of the Cre-loxP system to study tumorigenesis in the adult central nervous system (CNS can be limited, when the promoter (such as GFAP is also transiently expressed during development, which can result in the recombination of progenies of different lineages. Engineering of transgenic mice expressing Cre recombinase fused to a mutant of the human oestrogen receptor (ER allows the circumvention of transient developmental Cre expression by inducing recombination in the adult organism. The recombination of loxP sequences occurs only in the presence of tamoxifen. Systemic administration of tamoxifen can, however, exhibit toxicity and might also recombine unwanted cell populations if the promoter driving Cre expression is active at the time of tamoxifen administration. Here, we report that a single site-specific injection of an active derivative of tamoxifen successfully activates Cre recombinase and selectively recombines tumour suppressor genes in neural progenitor cells of the subventricular zone in mice, and we demonstrate its application in a model for the generation of intrinsic brain tumours.

  6. Generation of brain tumours in mice by Cre-mediated recombination of neural progenitors in situ with the tamoxifen metabolite endoxifen.

    Science.gov (United States)

    Benedykcinska, Anna; Ferreira, Andreia; Lau, Joanne; Broni, Jessica; Richard-Loendt, Angela; Henriquez, Nico V; Brandner, Sebastian

    2016-02-01

    Targeted cell- or region-specific gene recombination is widely used in the functional analysis of genes implicated in development and disease. In the brain, targeted gene recombination has become a mainstream approach to study neurodegeneration or tumorigenesis. The use of the Cre-loxP system to study tumorigenesis in the adult central nervous system (CNS) can be limited, when the promoter (such as GFAP) is also transiently expressed during development, which can result in the recombination of progenies of different lineages. Engineering of transgenic mice expressing Cre recombinase fused to a mutant of the human oestrogen receptor (ER) allows the circumvention of transient developmental Cre expression by inducing recombination in the adult organism. The recombination of loxP sequences occurs only in the presence of tamoxifen. Systemic administration of tamoxifen can, however, exhibit toxicity and might also recombine unwanted cell populations if the promoter driving Cre expression is active at the time of tamoxifen administration. Here, we report that a single site-specific injection of an active derivative of tamoxifen successfully activates Cre recombinase and selectively recombines tumour suppressor genes in neural progenitor cells of the subventricular zone in mice, and we demonstrate its application in a model for the generation of intrinsic brain tumours. © 2016. Published by The Company of Biologists Ltd.

  7. A potential neural substrate for processing functional classes of complex acoustic signals.

    Directory of Open Access Journals (Sweden)

    Isabelle George

    Full Text Available Categorization is essential to all cognitive processes, but identifying the neural substrates underlying categorization processes is a real challenge. Among animals that have been shown to be able of categorization, songbirds are particularly interesting because they provide researchers with clear examples of categories of acoustic signals allowing different levels of recognition, and they possess a system of specialized brain structures found only in birds that learn to sing: the song system. Moreover, an avian brain nucleus that is analogous to the mammalian secondary auditory cortex (the caudo-medial nidopallium, or NCM has recently emerged as a plausible site for sensory representation of birdsong, and appears as a well positioned brain region for categorization of songs. Hence, we tested responses in this non-primary, associative area to clear and distinct classes of songs with different functions and social values, and for a possible correspondence between these responses and the functional aspects of songs, in a highly social songbird species: the European starling. Our results clearly show differential neuronal responses to the ethologically defined classes of songs, both in the number of neurons responding, and in the response magnitude of these neurons. Most importantly, these differential responses corresponded to the functional classes of songs, with increasing activation from non-specific to species-specific and from species-specific to individual-specific sounds. These data therefore suggest a potential neural substrate for sorting natural communication signals into categories, and for individual vocal recognition of same-species members. Given the many parallels that exist between birdsong and speech, these results may contribute to a better understanding of the neural bases of speech.

  8. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination.

    Science.gov (United States)

    Zhao, Chunnian; Sun, GuoQiang; Li, Shengxiu; Shi, Yanhong

    2009-04-01

    MicroRNAs have been implicated as having important roles in stem cell biology. MicroRNA-9 (miR-9) is expressed specifically in neurogenic areas of the brain and may be involved in neural stem cell self-renewal and differentiation. We showed previously that the nuclear receptor TLX is an essential regulator of neural stem cell self-renewal. Here we show that miR-9 suppresses TLX expression to negatively regulate neural stem cell proliferation and accelerate neural differentiation. Introducing a TLX expression vector that is not prone to miR-9 regulation rescued miR-9-induced proliferation deficiency and inhibited precocious differentiation. In utero electroporation of miR-9 in embryonic brains led to premature differentiation and outward migration of the transfected neural stem cells. Moreover, TLX represses expression of the miR-9 pri-miRNA. By forming a negative regulatory loop with TLX, miR-9 provides a model for controlling the balance between neural stem cell proliferation and differentiation.

  9. Augmenting intracortical brain-machine interface with neurally driven error detectors

    Science.gov (United States)

    Even-Chen, Nir; Stavisky, Sergey D.; Kao, Jonathan C.; Ryu, Stephen I.; Shenoy, Krishna V.

    2017-12-01

    Objective. Making mistakes is inevitable, but identifying them allows us to correct or adapt our behavior to improve future performance. Current brain-machine interfaces (BMIs) make errors that need to be explicitly corrected by the user, thereby consuming time and thus hindering performance. We hypothesized that neural correlates of the user perceiving the mistake could be used by the BMI to automatically correct errors. However, it was unknown whether intracortical outcome error signals were present in the premotor and primary motor cortices, brain regions successfully used for intracortical BMIs. Approach. We report here for the first time a putative outcome error signal in spiking activity within these cortices when rhesus macaques performed an intracortical BMI computer cursor task. Main results. We decoded BMI trial outcomes shortly after and even before a trial ended with 96% and 84% accuracy, respectively. This led us to develop and implement in real-time a first-of-its-kind intracortical BMI error ‘detect-and-act’ system that attempts to automatically ‘undo’ or ‘prevent’ mistakes. The detect-and-act system works independently and in parallel to a kinematic BMI decoder. In a challenging task that resulted in substantial errors, this approach improved the performance of a BMI employing two variants of the ubiquitous Kalman velocity filter, including a state-of-the-art decoder (ReFIT-KF). Significance. Detecting errors in real-time from the same brain regions that are commonly used to control BMIs should improve the clinical viability of BMIs aimed at restoring motor function to people with paralysis.

  10. Decreased neural precursor cell pool in NADPH oxidase 2-deficiency: From mouse brain to neural differentiation of patient derived iPSC

    Directory of Open Access Journals (Sweden)

    Zeynab Nayernia

    2017-10-01

    Full Text Available There is emerging evidence for the involvement of reactive oxygen species (ROS in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC. High levels of NOX2 were found in mouse adult neurogenic regions. In NOX2-deficient mice, neurogenic regions showed diminished redox modifications, as well as decrease in neuroprecursor numbers and in expression of genes involved in neural differentiation including NES, BDNF and OTX2. iPSC from healthy subjects and patients with CGD were used to study the role of NOX2 in human in vitro neuronal development. Expression of NOX2 was low in undifferentiated iPSC, upregulated upon neural induction, and disappeared during neuronal differentiation. In human neurospheres, NOX2 protein and ROS generation were polarized within the inner cell layer of rosette structures. NOX2 deficiency in CGD-iPSCs resulted in an abnormal neural induction in vitro, as revealed by a reduced expression of neuroprogenitor markers (NES, BDNF, OTX2, NRSF/REST, and a decreased generation of mature neurons. Vector-mediated NOX2 expression in NOX2-deficient iPSCs rescued neurogenesis. Taken together, our study provides novel evidence for a regulatory role of NOX2 during early stages of neurogenesis in mouse and human.

  11. Brain Development

    Science.gov (United States)

    ... Become a Member Home Early Development & Well-Being Brain Development A child’s brain undergoes an amazing period of development from birth ... neural connections each second. The development of the brain is influenced by many factors, including a child’s ...

  12. Long-Term Alterations in Neural and Endocrine Processes Induced by Motherhood

    Science.gov (United States)

    Bridges, Robert S.

    2015-01-01

    The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female’s biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages. PMID:26388065

  13. Non-invasive Brain Stimulation: A Paradigm Shift in Understanding Brain Oscillations

    Directory of Open Access Journals (Sweden)

    Johannes Vosskuhl

    2018-05-01

    Full Text Available Cognitive neuroscience set out to understand the neural mechanisms underlying cognition. One central question is how oscillatory brain activity relates to cognitive processes. Up to now, most of the evidence supporting this relationship was correlative in nature. This situation changed dramatically with the recent development of non-invasive brain stimulation (NIBS techniques, which open up new vistas for neuroscience by allowing researchers for the first time to validate their correlational theories by manipulating brain functioning directly. In this review, we focus on transcranial alternating current stimulation (tACS, an electrical brain stimulation method that applies sinusoidal currents to the intact scalp of human individuals to directly interfere with ongoing brain oscillations. We outline how tACS can impact human brain oscillations by employing different levels of observation from non-invasive tACS application in healthy volunteers and intracranial recordings in patients to animal studies demonstrating the effectiveness of alternating electric fields on neurons in vitro and in vivo. These findings likely translate to humans as comparable effects can be observed in human and animal studies. Neural entrainment and plasticity are suggested to mediate the behavioral effects of tACS. Furthermore, we focus on mechanistic theories about the relationship between certain cognitive functions and specific parameters of brain oscillaitons such as its amplitude, frequency, phase and phase coherence. For each of these parameters we present the current state of testing its functional relevance by means of tACS. Recent developments in the field of tACS are outlined which include the stimulation with physiologically inspired non-sinusoidal waveforms, stimulation protocols which allow for the observation of online-effects, and closed loop applications of tACS.

  14. The Neural Basis of Changing Social Norms through Persuasion

    OpenAIRE

    Yomogida, Yukihito; Matsumoto, Madoka; Aoki, Ryuta; Sugiura, Ayaka; Phillips, Adam N.; Matsumoto, Kenji

    2017-01-01

    Social norms regulate behavior, and changes in norms have a great impact on society. In most modern societies, norms change through interpersonal communication and persuasive messages found in media. Here, we examined the neural basis of persuasion-induced changes in attitude toward and away from norms using fMRI. We measured brain activity while human participants were exposed to persuasive messages directed toward specific norms. Persuasion directed toward social norms specifically activate...

  15. Excretion of Different Forms of Zinc by the prawn Palaemon serratus (Pennant)

    International Nuclear Information System (INIS)

    Small, L.F.; Keckes, S.; Fowler, S.W.

    1976-01-01

    Freshly collected speciments of Palaemon serratus from the upper Adriatic Sea were used to determine excretion rates of zinc in ''zinc-free'' water by anodic stripping polarographic techniques. Weight-specific excretion of total zinc varied reciprocally with body weight apparently in a log-log relationship. Weight-specific excretion of ionic-particulate zinc appeared greatest in short term (1-3 hr) experiments, while weight specific excretion of complexed zinc appeared greatest in longer term (4-5 hr) experiments; however, we cannot exclude the possibility that ionic-particulate zinc and dissolved organic compounds were excreted separately and subsequently combined in the water to yield zinc complex. (author)

  16. Excretion of different forms of zinc by the prawn Palaemon serratus (Pennant)

    International Nuclear Information System (INIS)

    Small, L.F.; Keckes, S.; Fowler, S.W.

    1974-01-01

    Freshly collected specimens of Palaemon serratus from the upper Adriatic Sea were used to determine excretion rates of zinc in zinc-free water by anodic stripping polarographic techniques. Weight-specific excretion of total zinc varied reciprocally with body weight, apparently in a log--log relationship. Weight-specific excretion of ionic-particulate zinc appeared greatest in short term (1 to 3 hr) experiments, while weight-specific excretion of complexed zinc appeared greatest in longer term (4 to 5 hr) experiments; however, we cannot exclude the possibility that ionic-particulate zinc and dissolved organic compounds were excreted separately and subsequently combined in the water to yield zinc complex. (auth)

  17. The neural basis of unconditional love.

    Science.gov (United States)

    Beauregard, Mario; Courtemanche, Jérôme; Paquette, Vincent; St-Pierre, Evelyne Landry

    2009-05-15

    Functional neuroimaging studies have shown that romantic love and maternal love are mediated by regions specific to each, as well as overlapping regions in the brain's reward system. Nothing is known yet regarding the neural underpinnings of unconditional love. The main goal of this functional magnetic resonance imaging study was to identify the brain regions supporting this form of love. Participants were scanned during a control condition and an experimental condition. In the control condition, participants were instructed to simply look at a series of pictures depicting individuals with intellectual disabilities. In the experimental condition, participants were instructed to feel unconditional love towards the individuals depicted in a series of similar pictures. Significant loci of activation were found, in the experimental condition compared with the control condition, in the middle insula, superior parietal lobule, right periaqueductal gray, right globus pallidus (medial), right caudate nucleus (dorsal head), left ventral tegmental area and left rostro-dorsal anterior cingulate cortex. These results suggest that unconditional love is mediated by a distinct neural network relative to that mediating other emotions. This network contains cerebral structures known to be involved in romantic love or maternal love. Some of these structures represent key components of the brain's reward system.

  18. Time to address the problems at the neural interface

    Science.gov (United States)

    Durand, Dominique M.; Ghovanloo, Maysam; Krames, Elliot

    2014-04-01

    centered on interfacing with the CNS, it has recently become clear that the peripheral nervous system (PNS) could be an important target for interfacing, perhaps even more accessible for interfacing than the CNS. A recent initiative called Bioelectronic Medicines3 is a step in that direction. A recent summit held in New York was organized to investigate novel and disruptive neural technologies to interface specifically with the PNS in order to restore health and biological function to organs. With significant interest in neurotechnology for neural interfacing (see footnotes 1, 2 and 3) and uncovering new ways to treat, prevent and cure brain disorders (President Obama's brain initiative4), it seems clear that the problems at the interface will not remain unsolved for long. Finding solutions to the problem at the neural interface for interacting with the nervous system (PNS and CNS) is crucial for understanding and restoring brain function. This would in turn have a significant impact on health care and quality of life for patients with neural disorders. References [1] Follett K A et al 2010 Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease New Engl. J. Med. 362 2077-91 [2] Holtzheimer P E et al 2012 Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression Arch. Gen. Psychiatry 69 150 [3] Carron R, Chabardes S and Hammond C 2012 Mechanisms of action of high-frequency deep brain stimulation. A review of the literature and current concepts NeuroChirurgie 58 209-17 [4] Vidailhet M et al 2005 Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia New Engl. J. Med. 352 459-67 [5] Theodore W H and Fisher R S 2004 Brain stimulation for epilepsy Lancet Neurol. 3 111-8 [6] Kübler A, Kotchoubey B, Kaiser J, Wolpaw J R and Birbaumer N 2001 Brain-computer communication: unlocking the locked Psychol. Bull. 127 358-75 [7] Schalk G, Miller K J, Anderson N R, Wilson J A, Smyth M D

  19. Slc39a7/zip7 plays a critical role in development and zinc homeostasis in zebrafish.

    Directory of Open Access Journals (Sweden)

    Guang Yan

    Full Text Available BACKGROUND: Slc39a7/Zip7, also known as Ke4, is a member of solute carrier family 39 (Slc39a and plays a critical role in regulating cell growth and death. Because the function of Zip7 in vivo was unclear, the present study investigated the function of zip7 in vertebrate development and zinc metabolism using zebrafish as a model organism. PRINCIPAL FINDING: Using real-time PCR to determine the gene expression pattern of zip7 during zebrafish development, we found that zip7 mRNA is expressed throughout embryonic development and into maturity. Interestingly, whole mount in situ hybridization revealed that while zip7 mRNA is ubiquitously expressed until 12 hours post-fertilization (hpf; at 24 hpf and beyond, zip7 mRNA was specifically detected only in eyes. Morpholino-antisense (MO gene knockdown assay revealed that downregulation of zip7 expression resulted in several morphological defects in zebrafish including decreased head size, smaller eyes, shorter palates, and shorter and curved spinal cords. Analysis by synchrotron radiation X-ray fluorescence (SR-XRF showed reduced concentrations of zinc in brain, eyes, and gills of zip7-MO-injected embryos. Furthermore, incubation of the zip7 knockdown embryos in a zinc-supplemented solution was able to rescue the MO-induced morphological defects. SIGNIFICANCE: Our data suggest that zip7 is required for eye, brain, and skeleton formation during early embryonic development in zebrafish. Moreover, zinc supplementation can partially rescue defects resulting from zip7 gene knockdown. Taken together, our data provide critical insight into a novel function of zip7 in development and zinc homeostasis in vivo in zebrafish.

  20. Neural overlap in processing music and speech.

    Science.gov (United States)

    Peretz, Isabelle; Vuvan, Dominique; Lagrois, Marie-Élaine; Armony, Jorge L

    2015-03-19

    Neural overlap in processing music and speech, as measured by the co-activation of brain regions in neuroimaging studies, may suggest that parts of the neural circuitries established for language may have been recycled during evolution for musicality, or vice versa that musicality served as a springboard for language emergence. Such a perspective has important implications for several topics of general interest besides evolutionary origins. For instance, neural overlap is an important premise for the possibility of music training to influence language acquisition and literacy. However, neural overlap in processing music and speech does not entail sharing neural circuitries. Neural separability between music and speech may occur in overlapping brain regions. In this paper, we review the evidence and outline the issues faced in interpreting such neural data, and argue that converging evidence from several methodologies is needed before neural overlap is taken as evidence of sharing. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  1. The novel BTB/POZ and zinc finger factor Zbtb45 is essential for proper glial differentiation of neural and oligodendrocyte progenitor cells

    DEFF Research Database (Denmark)

    Södersten, Erik; Lilja, Tobias; Hermanson, Ola

    2010-01-01

    Understanding the regulatory mechanisms controlling the fate decisions of neural stem cells (NSCs) is a crucial issue to shed new light on mammalian central nervous system (CNS) development in health and disease. We have investigated a possible role for the previously uncharacterized BTB/POZ-doma......Understanding the regulatory mechanisms controlling the fate decisions of neural stem cells (NSCs) is a crucial issue to shed new light on mammalian central nervous system (CNS) development in health and disease. We have investigated a possible role for the previously uncharacterized BTB....../POZ-domain containing zinc finger factor Zbtb45 in the differentiation of NSCs and postnatal oligodendrocyte precursors. In situ hybridization histochemistry and RT-qPCR analysis revealed that Zbtb45 mRNA was ubiquitously expressed in the developing CNS in mouse embryos at embryonic day (E) 12.5 and 14.5. Zbtb45 m......RNA knockdown in embryonic forebrain NSCs by siRNA resulted in a rapid decrease in the expression of oligodendrocyte-characteristic genes after mitogen (FGF2) withdrawal, whereas the expression of astrocyte-associated genes such as CD44 and GFAP increased compared to control. Accordingly, the number...

  2. Brain imaging and memory systems in humans: the contribution of PET methods

    International Nuclear Information System (INIS)

    Perani, D.

    1998-01-01

    The development of neuroimaging methods such as PET, has provided a new impulse to the study of the neural basis of cognitive functions, and has extended the field of inquiry from the analysis of the consequences of brain lesions to the functional investigations of brain activity, either in patients with selective neuropsychological deficits or in normal subjects engaged in cognitive tasks. Specific patterns of hypo-metabolism in neurological patients are associated with different profiles of memory deficits.[ 18 F]FDG PET studies have confirmed the association of episodic memory with the structures of Papez's circuit and have shown correlations between short-term and semantic memory and the language areas. The identification of anatomical-functional networks involved in specific components of memory function in normal subjects is the aim of several PET activation studies. The results are in agreement with 'neural network' models of the neural basis of memory, as complex functions subserved by multiple interconnected cortical and subcortical structures. (author)

  3. Adolescent emotional maturation through divergent models of brain organization

    Directory of Open Access Journals (Sweden)

    Jose Víctor Orón Semper

    2016-08-01

    Full Text Available In this article we introduce the hypothesis that neuropsychological adolescent maturation, and in particular emotional management, may have opposing explanations depending on the interpretation of the assumed brain architecture, that is, whether a componential computational account (CCA or a dynamic systems perspective (DSP is used. According to CCA, cognitive functions are associated with the action of restricted brain regions, and this association is temporally stable; by contrast, DSP argues that cognitive functions are better explained by interactions between several brain areas, whose engagement in specific functions is temporal and context-dependent and based on neural reuse. We outline the main neurobiological facts about adolescent maturation, focusing on the neuroanatomical and neurofunctional processes associated with adolescence. We then explain the importance of emotional management in adolescent maturation. We explain the interplay between emotion and cognition under the scope of CCA and DSP, both at neural and behavioral levels. Finally, we justify why, according to CCA, emotional management is understood as regulation, specifically because the cognitive aspects of the brain are in charge of regulating emotion-related modules. However, the key word in DSP is integration, since neural information from different brain areas is integrated from the beginning of the process. Consequently, although the terms should not be conceptually confused, there is no cognition without emotion, and vice versa. Thus, emotional integration is not an independent process that just happens to the subject, but a crucial part of personal growth. Considering the importance of neuropsychological research in the development of educational and legal policies concerning adolescents, we intend to expose that the holistic view of adolescents is dependent on whether one holds the implicit or explicit interpretation of brain functioning.

  4. Primate brain architecture and selection in relation to sex.

    Science.gov (United States)

    Lindenfors, Patrik; Nunn, Charles L; Barton, Robert A

    2007-05-10

    Social and competitive demands often differ between the sexes in mammals. These differing demands should be expected to produce variation in the relative sizes of various brain structures. Sexual selection on males can be predicted to influence brain components handling sensory-motor skills that are important for physical competition or neural pathways involving aggression. Conversely, because female fitness is more closely linked to ecological factors and social interactions that enable better acquisition of resources, social selection on females should select for brain components important for navigating social networks. Sexual and social selection acting on one sex could produce sexual dimorphism in brain structures, which would result in larger species averages for those same brain structures. Alternatively, sex-specific selection pressures could produce correlated effects in the other sex, resulting in larger brain structures for both males and females of a species. Data are presently unavailable for the sex-specific sizes of brain structures for anthropoid primates, but under either scenario, the effects of sexual and social selection should leave a detectable signal in average sizes of brain structures for different species. The degree of male intra-sexual selection was positively correlated with several structures involved in autonomic functions and sensory-motor skills, and in pathways relating to aggression and aggression control. The degree of male intra-sexual selection was not correlated with relative neocortex size, which instead was significantly positively correlated with female social group size, but negatively correlated with male group size. Sexual selection on males and social selection on females have exerted different effects on primate brain architecture. Species with a higher degree of male intra-sexual selection carry a neural signature of an evolutionary history centered on physical conflicts, but no traces of increased demands on

  5. Primate brain architecture and selection in relation to sex

    Directory of Open Access Journals (Sweden)

    Nunn Charles L

    2007-05-01

    Full Text Available Abstract Background Social and competitive demands often differ between the sexes in mammals. These differing demands should be expected to produce variation in the relative sizes of various brain structures. Sexual selection on males can be predicted to influence brain components handling sensory-motor skills that are important for physical competition or neural pathways involving aggression. Conversely, because female fitness is more closely linked to ecological factors and social interactions that enable better acquisition of resources, social selection on females should select for brain components important for navigating social networks. Sexual and social selection acting on one sex could produce sexual dimorphism in brain structures, which would result in larger species averages for those same brain structures. Alternatively, sex-specific selection pressures could produce correlated effects in the other sex, resulting in larger brain structures for both males and females of a species. Data are presently unavailable for the sex-specific sizes of brain structures for anthropoid primates, but under either scenario, the effects of sexual and social selection should leave a detectable signal in average sizes of brain structures for different species. Results The degree of male intra-sexual selection was positively correlated with several structures involved in autonomic functions and sensory-motor skills, and in pathways relating to aggression and aggression control. The degree of male intra-sexual selection was not correlated with relative neocortex size, which instead was significantly positively correlated with female social group size, but negatively correlated with male group size. Conclusion Sexual selection on males and social selection on females have exerted different effects on primate brain architecture. Species with a higher degree of male intra-sexual selection carry a neural signature of an evolutionary history centered on

  6. Emerging trends in neuro engineering and neural computation

    CERN Document Server

    Lee, Kendall; Garmestani, Hamid; Lim, Chee

    2017-01-01

    This book focuses on neuro-engineering and neural computing, a multi-disciplinary field of research attracting considerable attention from engineers, neuroscientists, microbiologists and material scientists. It explores a range of topics concerning the design and development of innovative neural and brain interfacing technologies, as well as novel information acquisition and processing algorithms to make sense of the acquired data. The book also highlights emerging trends and advances regarding the applications of neuro-engineering in real-world scenarios, such as neural prostheses, diagnosis of neural degenerative diseases, deep brain stimulation, biosensors, real neural network-inspired artificial neural networks (ANNs) and the predictive modeling of information flows in neuronal networks. The book is broadly divided into three main sections including: current trends in technological developments, neural computation techniques to make sense of the neural behavioral data, and application of these technologie...

  7. Combined copper/zinc attachment to prion protein

    Science.gov (United States)

    Hodak, Miroslav; Bernholc, Jerry

    2013-03-01

    Misfolding of prion protein (PrP) is responsible for diseases such as ``mad-cow disease'' in cattle and Creutzfeldt-Jacob in humans. Extensive experimental investigation has established that this protein strongly interacts with copper ions, and this ability has been linked to its still unknown function. Attachment of other metal ions (zinc, iron, manganese) have been demonstrated as well, but none of them could outcompete copper. Recent finding, however, indicates that at intermediate concentrations both copper and zinc ions can attach to the PrP at the octarepeat region, which contains high affinity metal binding sites. Based on this evidence, we have performed density functional theory simulations to investigate the combined Cu/Zn attachment. We consider all previously reported binding modes of copper at the octarepeat region and examine a possibility simultaneous Cu/Zn attachment. We find that this can indeed occur for only one of the known binding sites, when copper changes its coordination mode to allow for attachment of zinc ion. The implications of the simultaneous attachment on neural function remain to be explored.

  8. Intra-cranial recordings of brain activity during language production

    Directory of Open Access Journals (Sweden)

    Anais eLlorens

    2011-12-01

    Full Text Available Recent findings in the neurophysiology of language production have provided a detailed description of the brain network underlying this behavior, as well as some indications about the timing of operations. Despite their invaluable utility, these data generally suffer from limitations either in terms of temporal resolution, or in terms of spatial localization. In addition, studying the neural basis of speech is complicated by the presence of articulation artifacts such as electro-myographic activity that interferes with the neural signal. These difficulties are virtually absent in a powerful albeit much less frequent methodology, namely the recording of intra-cranial brain activity (iEEG. Such recordings are only possible under very specific clinical circumstances requiring functional mapping before brain surgery, most notably patients that suffer for pharmaco-resistant epilepsy. Here we review the research conducted with this methodology in the field of language production, with explicit consideration of its advantages and drawbacks. The available evidence is shown to be diverse, both in terms of the tasks and cognitive processes tested and in terms of the brain localizations being studied. Still, the review provides valuable information for characterizing the dynamics of the neural events occurring in the language production network. Following modality specific activities (in auditory or visual cortices, there is a convergence of activity in superior temporal sulcus, which is a plausible neural correlate of phonological encoding processes. Later, between 500 and 800 ms, inferior frontal gyrus (around Broca's area is involved. Peri-rolandic areas are recruited in the two modalities relatively early (200-500 ms window, suggesting a very early involvement of (pre- motor processes. We discuss how some of these findings may be at odds with conclusions drawn from available meta-analysis of language production.

  9. Modal demultiplexing properties of tapered and nanostructured optical fibers for in vivo optogenetic control of neural activity.

    Science.gov (United States)

    Pisanello, Marco; Della Patria, Andrea; Sileo, Leonardo; Sabatini, Bernardo L; De Vittorio, Massimo; Pisanello, Ferruccio

    2015-10-01

    Optogenetic approaches to manipulate neural activity have revolutionized the ability of neuroscientists to uncover the functional connectivity underlying brain function. At the same time, the increasing complexity of in vivo optogenetic experiments has increased the demand for new techniques to precisely deliver light into the brain, in particular to illuminate selected portions of the neural tissue. Tapered and nanopatterned gold-coated optical fibers were recently proposed as minimally invasive multipoint light delivery devices, allowing for site-selective optogenetic stimulation in the mammalian brain [Pisanello , Neuron82, 1245 (2014)]. Here we demonstrate that the working principle behind these devices is based on the mode-selective photonic properties of the fiber taper. Using analytical and ray tracing models we model the finite conductance of the metal coating, and show that single or multiple optical windows located at specific taper sections can outcouple only specific subsets of guided modes injected into the fiber.

  10. The Neural Border: Induction, Specification and Maturation of the territory that generates Neural Crest cells.

    Science.gov (United States)

    Pla, Patrick; Monsoro-Burq, Anne H

    2018-05-28

    The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions. Copyright © 2018. Published by Elsevier Inc.

  11. Cracking the Neural Code for Sensory Perception by Combining Statistics, Intervention, and Behavior.

    Science.gov (United States)

    Panzeri, Stefano; Harvey, Christopher D; Piasini, Eugenio; Latham, Peter E; Fellin, Tommaso

    2017-02-08

    The two basic processes underlying perceptual decisions-how neural responses encode stimuli, and how they inform behavioral choices-have mainly been studied separately. Thus, although many spatiotemporal features of neural population activity, or "neural codes," have been shown to carry sensory information, it is often unknown whether the brain uses these features for perception. To address this issue, we propose a new framework centered on redefining the neural code as the neural features that carry sensory information used by the animal to drive appropriate behavior; that is, the features that have an intersection between sensory and choice information. We show how this framework leads to a new statistical analysis of neural activity recorded during behavior that can identify such neural codes, and we discuss how to combine intersection-based analysis of neural recordings with intervention on neural activity to determine definitively whether specific neural activity features are involved in a task. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 65Zinc and endogenous zinc content and distribution in islets in relationship to insulin content

    International Nuclear Information System (INIS)

    Figlewicz, D.P.; Forhan, S.E.; Hodgson, A.T.; Grodsky, G.M.

    1984-01-01

    Uptake of 65 Zn and distribution of 65 Zn, total zinc, and insulin were measured in rat islets and islet granules under different conditions of islet culture. Specific activity of islet zinc ( 65 Zn/zinc) was less than 15% that of extracellular zinc even after 48 h. In contrast, once in the islet, 65 Zn approached 70% of equilibrium with granular zinc in 24 h and apparent equilibrium by 48 h. During a 24-h culture, at either high or low glucose, reduction of both islet zinc and insulin occurred. However, zinc depletion was greater than that predicted if zinc loss was proportional to insulin depletion and occurred only from the granular compartment, which represents only one third of the total islet zinc. Extension of culture to 48 h caused additional insulin depletion, but islet zinc was unchanged. Omission of calcium during the 48-h culture caused a predicted increase in insulin retention, presumably by inhibiting secretion; however, zinc retention was not increased proportionately. Pretreatment of rats with tolbutamide caused a massive depletion of insulin stored in isolated islets, with little change in total islet zinc; subsequent culture of these islets resulted in a greater loss of granular zinc than predicted from the small loss of granular insulin. None of the conditions tested affected the percentage of either 65 Zn or total zinc that was distributed in the islet granules. Results show that zinc exists in a metabolically labile islet compartment(s) as well as in secretory granules; and extra-granular zinc, although not directly associated with insulin storage, may act as a reservoir for granular zinc and may regulate insulin synthesis, storage, and secretion in ways as yet unknown

  13. Neuromechanism study of insect-machine interface: flight control by neural electrical stimulation.

    Directory of Open Access Journals (Sweden)

    Huixia Zhao

    Full Text Available The insect-machine interface (IMI is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L. via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe, ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee-machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control.

  14. Neuromechanism study of insect-machine interface: flight control by neural electrical stimulation.

    Science.gov (United States)

    Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

    2014-01-01

    The insect-machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee-machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control.

  15. Neuromechanism Study of Insect–Machine Interface: Flight Control by Neural Electrical Stimulation

    Science.gov (United States)

    Zhao, Huixia; Zheng, Nenggan; Ribi, Willi A.; Zheng, Huoqing; Xue, Lei; Gong, Fan; Zheng, Xiaoxiang; Hu, Fuliang

    2014-01-01

    The insect–machine interface (IMI) is a novel approach developed for man-made air vehicles, which directly controls insect flight by either neuromuscular or neural stimulation. In our previous study of IMI, we induced flight initiation and cessation reproducibly in restrained honeybees (Apis mellifera L.) via electrical stimulation of the bilateral optic lobes. To explore the neuromechanism underlying IMI, we applied electrical stimulation to seven subregions of the honeybee brain with the aid of a new method for localizing brain regions. Results showed that the success rate for initiating honeybee flight decreased in the order: α-lobe (or β-lobe), ellipsoid body, lobula, medulla and antennal lobe. Based on a comparison with other neurobiological studies in honeybees, we propose that there is a cluster of descending neurons in the honeybee brain that transmits neural excitation from stimulated brain areas to the thoracic ganglia, leading to flight behavior. This neural circuit may involve the higher-order integration center, the primary visual processing center and the suboesophageal ganglion, which is also associated with a possible learning and memory pathway. By pharmacologically manipulating the electrically stimulated honeybee brain, we have shown that octopamine, rather than dopamine, serotonin and acetylcholine, plays a part in the circuit underlying electrically elicited honeybee flight. Our study presents a new brain stimulation protocol for the honeybee–machine interface and has solved one of the questions with regard to understanding which functional divisions of the insect brain participate in flight control. It will support further studies to uncover the involved neurons inside specific brain areas and to test the hypothesized involvement of a visual learning and memory pathway in IMI flight control. PMID:25409523

  16. Implantable neurotechnologies: a review of integrated circuit neural amplifiers.

    Science.gov (United States)

    Ng, Kian Ann; Greenwald, Elliot; Xu, Yong Ping; Thakor, Nitish V

    2016-01-01

    Neural signal recording is critical in modern day neuroscience research and emerging neural prosthesis programs. Neural recording requires the use of precise, low-noise amplifier systems to acquire and condition the weak neural signals that are transduced through electrode interfaces. Neural amplifiers and amplifier-based systems are available commercially or can be designed in-house and fabricated using integrated circuit (IC) technologies, resulting in very large-scale integration or application-specific integrated circuit solutions. IC-based neural amplifiers are now used to acquire untethered/portable neural recordings, as they meet the requirements of a miniaturized form factor, light weight and low power consumption. Furthermore, such miniaturized and low-power IC neural amplifiers are now being used in emerging implantable neural prosthesis technologies. This review focuses on neural amplifier-based devices and is presented in two interrelated parts. First, neural signal recording is reviewed, and practical challenges are highlighted. Current amplifier designs with increased functionality and performance and without penalties in chip size and power are featured. Second, applications of IC-based neural amplifiers in basic science experiments (e.g., cortical studies using animal models), neural prostheses (e.g., brain/nerve machine interfaces) and treatment of neuronal diseases (e.g., DBS for treatment of epilepsy) are highlighted. The review concludes with future outlooks of this technology and important challenges with regard to neural signal amplification.

  17. miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells.

    Science.gov (United States)

    Sun, GuoQiang; Ye, Peng; Murai, Kiyohito; Lang, Ming-Fei; Li, Shengxiu; Zhang, Heying; Li, Wendong; Fu, Chelsea; Yin, Jason; Wang, Allen; Ma, Xiaoxiao; Shi, Yanhong

    2011-11-08

    miR-137 is a brain-enriched microRNA. Its role in neural development remains unknown. Here we show that miR-137 has an essential role in controlling embryonic neural stem cell fate determination. miR-137 negatively regulates cell proliferation and accelerates neural differentiation of embryonic neural stem cells. In addition, we show that the histone lysine-specific demethylase 1 (LSD1), a transcriptional co-repressor of nuclear receptor TLX, is a downstream target of miR-137. In utero electroporation of miR-137 in embryonic mouse brains led to premature differentiation and outward migration of the transfected cells. Introducing a LSD1 expression vector lacking the miR-137 recognition site rescued miR-137-induced precocious differentiation. Furthermore, we demonstrate that TLX, an essential regulator of neural stem cell self-renewal, represses the expression of miR-137 by recruiting LSD1 to the genomic regions of miR-137. Thus, miR-137 forms a feedback regulatory loop with TLX and LSD1 to control the dynamics between neural stem cell proliferation and differentiation during neural development.

  18. Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation.

    Science.gov (United States)

    Paulk, Angelique C; Zhou, Yanqiong; Stratton, Peter; Liu, Li; van Swinderen, Bruno

    2013-10-01

    Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel "whole brain" readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior.

  19. Grand Research Plan for Neural Circuits of Emotion and Memory — Current status of neural circuit studies in China

    OpenAIRE

    Zhu, Yuan-Gui; Cao, He-Qi; Dong, Er-Dan

    2013-01-01

    During recent years, major advances have been made in neuroscience, i.e., asynchronous release, three-dimensional structural data sets, saliency maps, magnesium in brain research, and new functional roles of long non-coding RNAs. Especially, the development of optogenetic technology provides access to important information about relevant neural circuits by allowing the activation of specific neurons in awake mammals and directly observing the resulting behavior. The Grand Research Plan for Ne...

  20. Journal of Biosciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Zinc finger protein 521 is highly expressed in brain, neural stem cells and early ... Fndc5, a precursor of Irisin has inducing effects on the expression level of brain derived neurotrophic factor in hippocampus. ... Journal of Biosciences | News ...

  1. How motor, cognitive and musical expertise shapes the brain: Focus on fMRI and EEG resting-state functional connectivity

    DEFF Research Database (Denmark)

    Cantou, Pauline; Platel, Hervé; Desgranges, Béatrice

    2017-01-01

    about functional cerebral reorganization due to expertise at the whole-brain level and might facilitate comparison across studies. Resting-state functional MRI and EEG makes it possible to explore the functional traces of expertise in the brain by measuring temporal correlations of blood oxygen level......, to determine whether there is a domain-specific neural signature of expertise. After highlighting expertise-related changes within resting-state networks for each domain, we discuss their specificity to the trained activity and the methodological considerations concerning different conditions and analyses used......-dependent (BOLD) and spontaneous neural activity fluctuations at rest. Since these correlations are thought to reflect a prior history co-activation of brain regions, we propose reviewing studies that focused on the effects of expertise in the motor, cognitive and musical domains on brain plasticity at rest...

  2. Cross-cultural differences in the neural correlates of specific and general recognition.

    Science.gov (United States)

    Paige, Laura E; Ksander, John C; Johndro, Hunter A; Gutchess, Angela H

    2017-06-01

    Research suggests that culture influences how people perceive the world, which extends to memory specificity, or how much perceptual detail is remembered. The present study investigated cross-cultural differences (Americans vs East Asians) at the time of encoding in the neural correlates of specific versus general memory formation. Participants encoded photos of everyday items in the scanner and 48 h later completed a surprise recognition test. The recognition test consisted of same (i.e., previously seen in scanner), similar (i.e., same name, different features), or new photos (i.e., items not previously seen in scanner). For Americans compared to East Asians, we predicted greater activation in the hippocampus and right fusiform for specific memory at recognition, as these regions were implicated previously in encoding perceptual details. Results revealed that East Asians activated the left fusiform and left hippocampus more than Americans for specific versus general memory. Follow-up analyses ruled out alternative explanations of retrieval difficulty and familiarity for this pattern of cross-cultural differences at encoding. Results overall suggest that culture should be considered as another individual difference that affects memory specificity and modulates neural regions underlying these processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Olfactory systems and neural circuits that modulate predator odor fear

    Directory of Open Access Journals (Sweden)

    Lorey K. Takahashi

    2014-03-01

    Full Text Available When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS and accessory olfactory systems (AOS detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray, paraventricular nucleus of the hypothalamus, and the medial amygdala appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal stress hormone secretion. The medial amygdala also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus appear prominently involve in predator odor fear behavior. The basolateral amygdala, medial hypothalamic nuclei, and medial prefrontal cortex are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator odors activate

  4. Olfactory systems and neural circuits that modulate predator odor fear

    Science.gov (United States)

    Takahashi, Lorey K.

    2014-01-01

    When prey animals detect the odor of a predator a constellation of fear-related autonomic, endocrine, and behavioral responses rapidly occur to facilitate survival. How olfactory sensory systems process predator odor and channel that information to specific brain circuits is a fundamental issue that is not clearly understood. However, research in the last 15 years has begun to identify some of the essential features of the sensory detection systems and brain structures that underlie predator odor fear. For instance, the main (MOS) and accessory olfactory systems (AOS) detect predator odors and different types of predator odors are sensed by specific receptors located in either the MOS or AOS. However, complex predator chemosignals may be processed by both the MOS and AOS, which complicate our understanding of the specific neural circuits connected directly and indirectly from the MOS and AOS to activate the physiological and behavioral components of unconditioned and conditioned fear. Studies indicate that brain structures including the dorsal periaqueductal gray (DPAG), paraventricular nucleus (PVN) of the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in predator odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA) stress hormone secretion. The MeA also plays a key role in predator odor unconditioned fear behavior and retrieval of contextual fear memory associated with prior predator odor experiences. Other neural structures including the bed nucleus of the stria terminalis and the ventral hippocampus (VHC) appear prominently involved in predator odor fear behavior. The basolateral amygdala (BLA), medial hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some but not all predator odors. Future research that characterizes how distinct predator odors are uniquely processed in olfactory systems and neural circuits will provide significant insights into the differences of how diverse predator

  5. The two-brain approach: how can mutually interacting brains teach us something about social interaction?

    Directory of Open Access Journals (Sweden)

    Ivana eKonvalinka

    2012-07-01

    Full Text Available Measuring brain activity simultaneously from two people interacting is intuitively appealing if one is interested in putative neural markers of social interaction. However, given the complex nature of two-person interactions, it has proven difficult to carry out two-person brain imaging experiments in a methodologically feasible and conceptually relevant way. Only a small number of recent studies have put this into practice, using fMRI, EEG, or NIRS. Here, we review two main two-brain methodological approaches, each with two conceptual strategies. The first group has employed simultaneous fMRI recordings, studying a turn-based interactions on the order of seconds, or b pseudo-interactive scenarios, where only one person is scanned at a time, investigating the flow of information between brains. The second group of studies has recorded dual EEG/NIRS from two people interacting, in a face-to-face turn-based interactions, investigating functional connectivity between theory-of-mind regions of interacting partners, or in b continuous mutual interactions on millisecond timescales, to measure coupling between the activity in one person’s brain and the activity in the other’s brain. We discuss the questions these approaches have addressed, and consider scenarios when simultaneous two-brain recordings are needed. Furthermore, we suggest that a quantification of inter-personal neural effects via measures of emergence, and b multivariate decoding models that generalize source-specific features of interaction, may provide novel tools to study brains in interaction. This may allow for a better understanding of social cognition as both representation and participation.

  6. Neural Specialization for Speech in the First Months of Life

    Science.gov (United States)

    Shultz, Sarah; Vouloumanos, Athena; Bennett, Randi H.; Pelphrey, Kevin

    2014-01-01

    How does the brain's response to speech change over the first months of life? Although behavioral findings indicate that neonates' listening biases are sharpened over the first months of life, with a species-specific preference for speech emerging by 3 months, the neural substrates underlying this developmental change are unknown. We…

  7. Auto-Context Convolutional Neural Network (Auto-Net) for Brain Extraction in Magnetic Resonance Imaging.

    Science.gov (United States)

    Mohseni Salehi, Seyed Sadegh; Erdogmus, Deniz; Gholipour, Ali

    2017-11-01

    Brain extraction or whole brain segmentation is an important first step in many of the neuroimage analysis pipelines. The accuracy and the robustness of brain extraction, therefore, are crucial for the accuracy of the entire brain analysis process. The state-of-the-art brain extraction techniques rely heavily on the accuracy of alignment or registration between brain atlases and query brain anatomy, and/or make assumptions about the image geometry, and therefore have limited success when these assumptions do not hold or image registration fails. With the aim of designing an accurate, learning-based, geometry-independent, and registration-free brain extraction tool, in this paper, we present a technique based on an auto-context convolutional neural network (CNN), in which intrinsic local and global image features are learned through 2-D patches of different window sizes. We consider two different architectures: 1) a voxelwise approach based on three parallel 2-D convolutional pathways for three different directions (axial, coronal, and sagittal) that implicitly learn 3-D image information without the need for computationally expensive 3-D convolutions and 2) a fully convolutional network based on the U-net architecture. Posterior probability maps generated by the networks are used iteratively as context information along with the original image patches to learn the local shape and connectedness of the brain to extract it from non-brain tissue. The brain extraction results we have obtained from our CNNs are superior to the recently reported results in the literature on two publicly available benchmark data sets, namely, LPBA40 and OASIS, in which we obtained the Dice overlap coefficients of 97.73% and 97.62%, respectively. Significant improvement was achieved via our auto-context algorithm. Furthermore, we evaluated the performance of our algorithm in the challenging problem of extracting arbitrarily oriented fetal brains in reconstructed fetal brain magnetic

  8. A realistic neural mass model of the cortex with laminar-specific connections and synaptic plasticity - evaluation with auditory habituation.

    Directory of Open Access Journals (Sweden)

    Peng Wang

    Full Text Available In this work we propose a biologically realistic local cortical circuit model (LCCM, based on neural masses, that incorporates important aspects of the functional organization of the brain that have not been covered by previous models: (1 activity dependent plasticity of excitatory synaptic couplings via depleting and recycling of neurotransmitters and (2 realistic inter-laminar dynamics via laminar-specific distribution of and connections between neural populations. The potential of the LCCM was demonstrated by accounting for the process of auditory habituation. The model parameters were specified using Bayesian inference. It was found that: (1 besides the major serial excitatory information pathway (layer 4 to layer 2/3 to layer 5/6, there exists a parallel "short-cut" pathway (layer 4 to layer 5/6, (2 the excitatory signal flow from the pyramidal cells to the inhibitory interneurons seems to be more intra-laminar while, in contrast, the inhibitory signal flow from inhibitory interneurons to the pyramidal cells seems to be both intra- and inter-laminar, and (3 the habituation rates of the connections are unsymmetrical: forward connections (from layer 4 to layer 2/3 are more strongly habituated than backward connections (from Layer 5/6 to layer 4. Our evaluation demonstrates that the novel features of the LCCM are of crucial importance for mechanistic explanations of brain function. The incorporation of these features into a mass model makes them applicable to modeling based on macroscopic data (like EEG or MEG, which are usually available in human experiments. Our LCCM is therefore a valuable building block for future realistic models of human cognitive function.

  9. Consciousness and neural plasticity

    DEFF Research Database (Denmark)

    changes or to abandon the strong identity thesis altogether. Were one to pursue a theory according to which consciousness is not an epiphenomenon to brain processes, consciousness may in fact affect its own neural basis. The neural correlate of consciousness is often seen as a stable structure, that is...

  10. Molecular control of brain size: Regulators of neural stem cell life, death and beyond

    International Nuclear Information System (INIS)

    Joseph, Bertrand; Hermanson, Ola

    2010-01-01

    The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas members of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.

  11. Molecular control of brain size: Regulators of neural stem cell life, death and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, Bertrand [Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Stockholm (Sweden); Hermanson, Ola, E-mail: ola.hermanson@ki.se [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, Stockholm (Sweden)

    2010-05-01

    The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas members of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.

  12. Development and aging of a brain neural stem cell niche.

    Science.gov (United States)

    Conover, Joanne C; Todd, Krysti L

    2017-08-01

    In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear. Here, we review functional and organizational differences in the V-SVZ stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche and its associated functions. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Distinct contributions of functional and deep neural network features to representational similarity of scenes in human brain and behavior.

    Science.gov (United States)

    Groen, Iris Ia; Greene, Michelle R; Baldassano, Christopher; Fei-Fei, Li; Beck, Diane M; Baker, Chris I

    2018-03-07

    Inherent correlations between visual and semantic features in real-world scenes make it difficult to determine how different scene properties contribute to neural representations. Here, we assessed the contributions of multiple properties to scene representation by partitioning the variance explained in human behavioral and brain measurements by three feature models whose inter-correlations were minimized a priori through stimulus preselection. Behavioral assessments of scene similarity reflected unique contributions from a functional feature model indicating potential actions in scenes as well as high-level visual features from a deep neural network (DNN). In contrast, similarity of cortical responses in scene-selective areas was uniquely explained by mid- and high-level DNN features only, while an object label model did not contribute uniquely to either domain. The striking dissociation between functional and DNN features in their contribution to behavioral and brain representations of scenes indicates that scene-selective cortex represents only a subset of behaviorally relevant scene information.

  14. Anger in brain and body: the neural and physiological perturbation of decision-making by emotion.

    Science.gov (United States)

    Garfinkel, Sarah N; Zorab, Emma; Navaratnam, Nakulan; Engels, Miriam; Mallorquí-Bagué, Núria; Minati, Ludovico; Dowell, Nicholas G; Brosschot, Jos F; Thayer, Julian F; Critchley, Hugo D

    2016-01-01

    Emotion and cognition are dynamically coupled to bodily arousal: the induction of anger, even unconsciously, can reprioritise neural and physiological resources toward action states that bias cognitive processes. Here we examine behavioural, neural and bodily effects of covert anger processing and its influence on cognition, indexed by lexical decision-making. While recording beat-to-beat blood pressure, the words ANGER or RELAX were presented subliminally just prior to rapid word/non-word reaction-time judgements of letter-strings. Subliminal ANGER primes delayed the time taken to reach rapid lexical decisions, relative to RELAX primes. However, individuals with high trait anger were speeded up by subliminal anger primes. ANGER primes increased systolic blood pressure and the magnitude of this increase predicted reaction time prolongation. Within the brain, ANGER trials evoked an enhancement of activity within dorsal pons and an attenuation of activity within visual occipitotemporal and attentional parietal cortices. Activity within periaqueductal grey matter, occipital and parietal regions increased linearly with evoked blood pressure changes, indicating neural substrates through which covert anger impairs semantic decisions, putatively through its expression as visceral arousal. The behavioural and physiological impact of anger states compromises the efficiency of cognitive processing through action-ready changes in autonomic response that skew regional neural activity. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. Separate neural mechanisms underlie choices and strategic preferences in risky decision making.

    Science.gov (United States)

    Venkatraman, Vinod; Payne, John W; Bettman, James R; Luce, Mary Frances; Huettel, Scott A

    2009-05-28

    Adaptive decision making in real-world contexts often relies on strategic simplifications of decision problems. Yet, the neural mechanisms that shape these strategies and their implementation remain largely unknown. Using an economic decision-making task, we dissociate brain regions that predict specific choices from those predicting an individual's preferred strategy. Choices that maximized gains or minimized losses were predicted by functional magnetic resonance imaging activation in ventromedial prefrontal cortex or anterior insula, respectively. However, choices that followed a simplifying strategy (i.e., attending to overall probability of winning) were associated with activation in parietal and lateral prefrontal cortices. Dorsomedial prefrontal cortex, through differential functional connectivity with parietal and insular cortex, predicted individual variability in strategic preferences. Finally, we demonstrate that robust decision strategies follow from neural sensitivity to rewards. We conclude that decision making reflects more than compensatory interaction of choice-related regions; in addition, specific brain systems potentiate choices depending on strategies, traits, and context.

  16. Characterization and chondrocyte differentiation stage-specific expression of KRAB zinc-finger protein gene ZNF470

    International Nuclear Information System (INIS)

    Hering, Thomas M.; Kazmi, Najam H.; Huynh, Tru D.; Kollar, John; Xu, Laura; Hunyady, Aaron B.; Johnstone, Brian

    2004-01-01

    As part of a study to identify novel transcriptional regulators of chondrogenesis-related gene expression, we have cloned and characterized cDNA for zinc-finger protein 470 (ZNF470), the human ortholog of which encodes a 717 amino acid residue protein containing 17 Cys 2 His 2 zinc-finger domains, as well as KRAB-A and KRAB-B motifs. The cDNA library used to isolate the initial ZNF470 clone was prepared from human bone marrow-derived mesenchymal progenitor cells at an intermediate stage of chondrogenic differentiation. We have determined the intron-exon structure of the human ZNF470 gene, which has been mapped to a zinc-finger cluster in a known imprinted region of human chromosome 19q13.4. ZNF470 is expressed at high levels in human testis and is expressed at low or undetectible levels in other adult tissues. Human ZNF470 expressed in mammalian cells as an EGFP fusion protein localizes predominantly to the nucleus, consistent with a role in transcriptional regulation. ZNF470, analyzed by quantitative real time PCR, was transiently expressed before the maximal expression of COL2A1 during chondrogenic differentiation in vitro. We have also characterized the bovine ortholog of human ZNF470, which encodes a 508 amino acid residue protein having 10 zinc-finger domains. A bovine ZNF470 cDNA clone was used to examine expression of ZNF470 in bovine articular chondrocytes treated with retinoic acid to stimulate dedifferentiation. Bovine ZNF470 expression was undetectable in freshly isolated bovine articular chondrocytes, but was dramatically upregulated in dedifferentiated retinoic acid-treated chondrocytes. These results, in two model systems, suggest a possible role for ZNF470 in the regulation of chondrogenesis-specific gene expression

  17. Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

    Science.gov (United States)

    Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

    2013-01-01

    Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

  18. Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain

    Directory of Open Access Journals (Sweden)

    Marina E. Emborg

    2013-03-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies.

  19. Using imagination to understand the neural basis of episodic memory

    Science.gov (United States)

    Hassabis, Demis; Kumaran, Dharshan; Maguire, Eleanor A.

    2008-01-01

    Functional MRI (fMRI) studies investigating the neural basis of episodic memory recall, and the related task of thinking about plausible personal future events, have revealed a consistent network of associated brain regions. Surprisingly little, however, is understood about the contributions individual brain areas make to the overall recollective experience. In order to examine this, we employed a novel fMRI paradigm where subjects had to imagine fictitious experiences. In contrast to future thinking, this results in experiences that are not explicitly temporal in nature or as reliant on self-processing. By using previously imagined fictitious experiences as a comparison for episodic memories, we identified the neural basis of a key process engaged in common, namely scene construction, involving the generation, maintenance and visualisation of complex spatial contexts. This was associated with activations in a distributed network, including hippocampus, parahippocampal gyrus, and retrosplenial cortex. Importantly, we disambiguated these common effects from episodic memory-specific responses in anterior medial prefrontal cortex, posterior cingulate cortex and precuneus. These latter regions may support self-schema and familiarity processes, and contribute to the brain's ability to distinguish real from imaginary memories. We conclude that scene construction constitutes a common process underlying episodic memory and imagination of fictitious experiences, and suggest it may partially account for the similar brain networks implicated in navigation, episodic future thinking, and the default mode. We suggest that further brain regions are co-opted into this core network in a task-specific manner to support functions such as episodic memory that may have additional requirements. PMID:18160644

  20. Uptake and partitioning of zinc in Lemnaceae.

    Science.gov (United States)

    Lahive, Elma; O'Callaghan, Michael J A; Jansen, Marcel A K; O'Halloran, John

    2011-11-01

    Macrophytes provide food and shelter for aquatic invertebrates and fish, while also acting as reservoirs for nutrients and trace elements. Zinc accumulation has been reported for various Lemnaceae species. However, comparative accumulation across species and the link between zinc accumulation and toxicity are poorly understood. Morphological distribution and cellular storage, in either bound or soluble form, are important for zinc tolerance. This study shows differences in the uptake and accumulation of zinc by three duckweed species. Landoltia punctata and Lemna minor generally accumulated more zinc than Lemna gibba. L. minor, but not L. gibba or L. punctata, accumulated greater concentrations of zinc in roots compared to fronds when exposed to high levels of zinc. The proportion of zinc stored in the bound form relative to the soluble-form was higher in L. minor. L. punctata accumulated greater concentrations of zinc in fronds compared to roots and increased the proportion of zinc it stored in the soluble form, when exposed to high zinc levels. L. gibba is the only species that significantly accumulated zinc at low concentrations, and was zinc-sensitive. Overall, internal zinc concentrations showed no consistent correlation with toxic effect. We conclude that relationships between zinc toxicity and uptake and accumulation are species specific reflecting, among others, zinc distribution and storage. Differences in zinc distribution and storage are also likely to have implications for zinc bioavailability and trophic mobility.

  1. An Attractor-Based Complexity Measurement for Boolean Recurrent Neural Networks

    Science.gov (United States)

    Cabessa, Jérémie; Villa, Alessandro E. P.

    2014-01-01

    We provide a novel refined attractor-based complexity measurement for Boolean recurrent neural networks that represents an assessment of their computational power in terms of the significance of their attractor dynamics. This complexity measurement is achieved by first proving a computational equivalence between Boolean recurrent neural networks and some specific class of -automata, and then translating the most refined classification of -automata to the Boolean neural network context. As a result, a hierarchical classification of Boolean neural networks based on their attractive dynamics is obtained, thus providing a novel refined attractor-based complexity measurement for Boolean recurrent neural networks. These results provide new theoretical insights to the computational and dynamical capabilities of neural networks according to their attractive potentialities. An application of our findings is illustrated by the analysis of the dynamics of a simplified model of the basal ganglia-thalamocortical network simulated by a Boolean recurrent neural network. This example shows the significance of measuring network complexity, and how our results bear new founding elements for the understanding of the complexity of real brain circuits. PMID:24727866

  2. Endogenous neurogenesis in the human brain following cerebral infarction.

    Science.gov (United States)

    Minger, Stephen L; Ekonomou, Antigoni; Carta, Eloisa M; Chinoy, Amish; Perry, Robert H; Ballard, Clive G

    2007-01-01

    Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but there have been very few studies in humans. We therefore examined whether there was evidence of altered endogenous neurogenesis in an 84-year-old patient who suffered a cerebrovascular accident 1 week prior to death. Using antibodies that specifically label neural stem/neural progenitor cells, we examined the presence of immunopositive cells around and distant from the infarcted area, and compared this with a control, age-matched individual. Interestingly, a large number of neural stem cells, vascular endothelial growth factor-immunopositive cells and new blood vessels were observed only around the region of infarction, and none in the corresponding brain areas of the healthy control. In addition, an increased number of neural stem cells was observed in the neurogenic region of the lateral ventricle wall. Our results suggest increased endogenous neurogenesis associated with neovascularization and migration of newly-formed cells towards a region of cerebrovascular damage in the adult human brain and highlight possible mechanisms underlying this process.

  3. Oxytocin receptor polymorphism and childhood social experiences shape adult personality, brain structure and neural correlates of mentalizing.

    Science.gov (United States)

    Schneider-Hassloff, H; Straube, B; Jansen, A; Nuscheler, B; Wemken, G; Witt, S H; Rietschel, M; Kircher, T

    2016-07-01

    The oxytocin system is involved in human social behavior and social cognition such as attachment, emotion recognition and mentalizing (i.e. the ability to represent mental states of oneself and others). It is shaped by social experiences in early life, especially by parent-infant interactions. The single nucleotid polymorphism rs53576 in the oxytocin receptor (OXTR) gene has been linked to social behavioral phenotypes. In 195 adult healthy subjects we investigated the interaction of OXTR rs53576 and childhood attachment security (CAS) on the personality traits "adult attachment style" and "alexithymia" (i.e. emotional self-awareness), on brain structure (voxel-based morphometry) and neural activation (fMRI) during an interactive mentalizing paradigm (prisoner's dilemma game; subgroup: n=163). We found that in GG-homozygotes, but not in A-allele carriers, insecure childhood attachment is - in adulthood - associated with a) higher attachment-related anxiety and alexithymia, b) higher brain gray matter volume of left amygdala and lower volumes in right superior parietal lobule (SPL), left temporal pole (TP), and bilateral frontal regions, and c) higher mentalizing-related neural activity in bilateral TP and precunei, and right middle and superior frontal gyri. Interaction effects of genotype and CAS on brain volume and/or function were associated with individual differences in alexithymia and attachment-related anxiety. Interactive effects were in part sexually dimorphic. The interaction of OXTR genotype and CAS modulates adult personality as well as brain structure and function of areas implicated in salience processing and mentalizing. Rs53576 GG-homozygotes are partially more susceptible to childhood attachment experiences than A-allele carriers. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Principles of neural information processing

    CERN Document Server

    Seelen, Werner v

    2016-01-01

    In this fundamental book the authors devise a framework that describes the working of the brain as a whole. It presents a comprehensive introduction to the principles of Neural Information Processing as well as recent and authoritative research. The books´ guiding principles are the main purpose of neural activity, namely, to organize behavior to ensure survival, as well as the understanding of the evolutionary genesis of the brain. Among the developed principles and strategies belong self-organization of neural systems, flexibility, the active interpretation of the world by means of construction and prediction as well as their embedding into the world, all of which form the framework of the presented description. Since, in brains, their partial self-organization, the lifelong adaptation and their use of various methods of processing incoming information are all interconnected, the authors have chosen not only neurobiology and evolution theory as a basis for the elaboration of such a framework, but also syst...

  5. Neural tension technique is no different from random passive movements in reducing spasticity in patients with traumatic brain injury

    DEFF Research Database (Denmark)

    Lorentzen, Jakob; Nielsen, Dorthe; Holm, Karl

    2012-01-01

    Purpose: Neural tension technique (NTT) is a therapy believed to reduce spasticity and to increase range of motion (ROM). This study compared the ability of NTT and random passive movements (RPMs) to reduce spasticity in the knee flexors in 10 spastic patients with brain injury. Methods: An RCT...

  6. A cell junction pathology of neural stem cells leads to abnormal neurogenesis and hydrocephalus

    Directory of Open Access Journals (Sweden)

    Esteban M Rodríguez

    2012-01-01

    Full Text Available Most cells of the developing mammalian brain derive from the ventricular (VZ and the subventricular (SVZ zones. The VZ is formed by the multipotent radial glia/neural stem cells (NSCs while the SVZ harbors the rapidly proliferative neural precursor cells (NPCs. Evidence from human and animal models indicates that the common history of hydrocephalus and brain maldevelopment starts early in embryonic life with disruption of the VZ and SVZ. We propose that a "cell junction pathology" involving adherent and gap junctions is a final common outcome of a wide range of gene mutations resulting in proteins abnormally expressed by the VZ cells undergoing disruption. Disruption of the VZ during fetal development implies the loss of NSCs whereas VZ disruption during the perinatal period implies the loss of ependyma. The process of disruption occurs in specific regions of the ventricular system and at specific stages of brain development. This explains why only certain brain structures have an abnormal development, which in turn results in a specific neurological impairment of the newborn. Disruption of the VZ of the Sylvian aqueduct (SA leads to aqueductal stenosis and hydrocephalus, while disruption of the VZ of telencephalon impairs neurogenesis. We are currently investigating whether grafting of NSCs/neurospheres from normal rats into the CSF of hydrocephalic mutants helps to diminish/repair the outcomes of VZ disruption.

  7. Using Expectancy Theory to quantitatively dissociate the neural representation of motivation from its influential factors in the human brain: An fMRI study.

    Science.gov (United States)

    Kohli, Akshay; Blitzer, David N; Lefco, Ray W; Barter, Joseph W; Haynes, M Ryan; Colalillo, Sam A; Ly, Martina; Zink, Caroline F

    2018-05-08

    Researchers have yet to apply a formal operationalized theory of motivation to neurobiology that would more accurately and precisely define neural activity underlying motivation. We overcome this challenge with the novel application of the Expectancy Theory of Motivation to human fMRI to identify brain activity that explicitly reflects motivation. Expectancy Theory quantitatively describes how individual constructs determine motivation by defining motivation force as the product of three variables: expectancy - belief that effort will better performance; instrumentality - belief that successful performance leads to particular outcome, and valence - outcome desirability. Here, we manipulated information conveyed by reward-predicting cues such that relative cue-evoked activity patterns could be statistically mapped to individual Expectancy Theory variables. The variable associated with activity in any voxel is only reported if it replicated between two groups of healthy participants. We found signals in midbrain, ventral striatum, sensorimotor cortex, and visual cortex that specifically map to motivation itself, rather than other factors. This is important because, for the first time, it empirically clarifies approach motivation neural signals during reward anticipation. It also highlights the effectiveness of the application of Expectancy Theory to neurobiology to more precisely and accurately probe motivation neural correlates than has been achievable previously. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Calcium, potassium, iron, copper and zinc concentrations in the white and gray matter of the cerebellum and corpus callosum in brain of four genetic mouse strains

    International Nuclear Information System (INIS)

    Sergeant, C.; Vesvres, M.H.; Deves, G.; Guillou, F.

    2005-01-01

    In the central nervous system, metallic cations are involved in oligodendrocyte maturation and myelinogenesis. Moreover, the metallic cations have been associated with pathogenesis, particularly multiple sclerosis and malignant gliomas. The brain is vulnerable to either a deficit or an excess of available trace elements. Relationship between trace metals and myelinogenesis is important in understanding a severe human pathology : the multiple sclerosis, which remains without efficient treatment. One approach to understand this disease has used mutant or transgenic mice presenting myelin deficiency or excess. But to date, the concentration of trace metals and mineral elements in white and gray matter areas in wild type brain is unknown. The aim of this study is to establish the reference concentrations of trace metals (iron, copper and zinc) and minerals (potassium and calcium) in the white and gray matter of the mouse cerebellum and corpus callosum. The brains of four different genetic mouse strains (C57Black6/SJL, C57Black6/D2, SJL and C3H) were analyzed. The freeze-dried samples were prepared to allow PIXE (Proton-induced X-ray emission) and RBS (Rutherford backscattering spectrometry) analyses with the nuclear microprobe in Bordeaux. The results obtained give the first reference values. Furthermore, one species out of the fours testes exhibited differences in calcium, iron and zinc concentrations in the white matter

  9. Calcium, potassium, iron, copper and zinc concentrations in the white and gray matter of the cerebellum and corpus callosum in brain of four genetic mouse strains

    Energy Technology Data Exchange (ETDEWEB)

    Sergeant, C. [CNRS-Universite de Bordeaux I, UMR 5084, Chimie Nucleaire Analytique et Bio environnementale, Le Haut Vigneau, BP120, 33175 Bordeaux-Gradignan (France)]. E-mail: sergeant@cenbg.in2p3.fr; Vesvres, M.H. [CNRS-Universite de Bordeaux I, UMR 5084, Chimie Nucleaire Analytique et Bio environnementale, Le Haut Vigneau, BP120, 33175 Bordeaux-Gradignan (France); Deves, G. [CNRS-Universite de Bordeaux I, UMR 5084, Chimie Nucleaire Analytique et Bio environnementale, Le Haut Vigneau, BP120, 33175 Bordeaux-Gradignan (France); Guillou, F. [INRA-CNRS-Universite de Tours-Haras nationaux, UMR 6175, Physiologie de la Reproduction et des Comportements, 37380 Nouzilly (France)

    2005-04-01

    In the central nervous system, metallic cations are involved in oligodendrocyte maturation and myelinogenesis. Moreover, the metallic cations have been associated with pathogenesis, particularly multiple sclerosis and malignant gliomas. The brain is vulnerable to either a deficit or an excess of available trace elements. Relationship between trace metals and myelinogenesis is important in understanding a severe human pathology : the multiple sclerosis, which remains without efficient treatment. One approach to understand this disease has used mutant or transgenic mice presenting myelin deficiency or excess. But to date, the concentration of trace metals and mineral elements in white and gray matter areas in wild type brain is unknown. The aim of this study is to establish the reference concentrations of trace metals (iron, copper and zinc) and minerals (potassium and calcium) in the white and gray matter of the mouse cerebellum and corpus callosum. The brains of four different genetic mouse strains (C57Black6/SJL, C57Black6/D2, SJL and C3H) were analyzed. The freeze-dried samples were prepared to allow PIXE (Proton-induced X-ray emission) and RBS (Rutherford backscattering spectrometry) analyses with the nuclear microprobe in Bordeaux. The results obtained give the first reference values. Furthermore, one species out of the fours testes exhibited differences in calcium, iron and zinc concentrations in the white matter.

  10. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    Science.gov (United States)

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-09

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Region-specific protein misfolding cyclic amplification reproduces brain tropism of prion strains.

    Science.gov (United States)

    Privat, Nicolas; Levavasseur, Etienne; Yildirim, Serfildan; Hannaoui, Samia; Brandel, Jean-Philippe; Laplanche, Jean-Louis; Béringue, Vincent; Seilhean, Danielle; Haïk, Stéphane

    2017-10-06

    Human prion diseases such as Creutzfeldt-Jakob disease are transmissible brain proteinopathies, characterized by the accumulation of a misfolded isoform of the host cellular prion protein (PrP) in the brain. According to the prion model, prions are defined as proteinaceous infectious particles composed solely of this abnormal isoform of PrP (PrP Sc ). Even in the absence of genetic material, various prion strains can be propagated in experimental models. They can be distinguished by the pattern of disease they produce and especially by the localization of PrP Sc deposits within the brain and the spongiform lesions they induce. The mechanisms involved in this strain-specific targeting of distinct brain regions still are a fundamental, unresolved question in prion research. To address this question, we exploited a prion conversion in vitro assay, protein misfolding cyclic amplification (PMCA), by using experimental scrapie and human prion strains as seeds and specific brain regions from mice and humans as substrates. We show here that region-specific PMCA in part reproduces the specific brain targeting observed in experimental, acquired, and sporadic Creutzfeldt-Jakob diseases. Furthermore, we provide evidence that, in addition to cellular prion protein, other region- and species-specific molecular factors influence the strain-dependent prion conversion process. This important step toward understanding prion strain propagation in the human brain may impact research on the molecular factors involved in protein misfolding and the development of ultrasensitive methods for diagnosing prion disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. The fiber-optic imaging and manipulation of neural activity during animal behavior.

    Science.gov (United States)

    Miyamoto, Daisuke; Murayama, Masanori

    2016-02-01

    Recent progress with optogenetic probes for imaging and manipulating neural activity has further increased the relevance of fiber-optic systems for neural circuitry research. Optical fibers, which bi-directionally transmit light between separate sites (even at a distance of several meters), can be used for either optical imaging or manipulating neural activity relevant to behavioral circuitry mechanisms. The method's flexibility and the specifications of the light structure are well suited for following the behavior of freely moving animals. Furthermore, thin optical fibers allow researchers to monitor neural activity from not only the cortical surface but also deep brain regions, including the hippocampus and amygdala. Such regions are difficult to target with two-photon microscopes. Optogenetic manipulation of neural activity with an optical fiber has the advantage of being selective for both cell-types and projections as compared to conventional electrophysiological brain tissue stimulation. It is difficult to extract any data regarding changes in neural activity solely from a fiber-optic manipulation device; however, the readout of data is made possible by combining manipulation with electrophysiological recording, or the simultaneous application of optical imaging and manipulation using a bundle-fiber. The present review introduces recent progress in fiber-optic imaging and manipulation methods, while also discussing fiber-optic system designs that are suitable for a given experimental protocol. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  13. Genome-wide analysis of the CCCH zinc finger family identifies tissue specific and stress responsive candidates in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Pradhan, Seema; Kant, Chandra; Verma, Subodh; Bhatia, Sabhyata

    2017-01-01

    The CCCH zinc finger is a group of proteins characterised by a typical motif consisting of three cysteine residues and one histidine residue. These proteins have been reported to play important roles in regulation of plant growth, developmental processes and environmental responses. In the present study, genome wide analysis of the CCCH zinc finger gene family was carried out in the available chickpea genome. Various bioinformatics tools were employed to predict 58 CCCH zinc finger genes in chickpea (designated CarC3H1-58), which were analysed for their physio-chemical properties. Phylogenetic analysis classified the proteins into 12 groups in which members of a particular group had similar structural organization. Further, the numbers as well as the types of CCCH motifs present in the CarC3H proteins were compared with those from Arabidopsis and Medicago truncatula. Synteny analysis revealed valuable information regarding the evolution of this gene family. Tandem and segmental duplication events were identified and their Ka/Ks values revealed that the CarC3H gene family in chickpea had undergone purifying selection. Digital, as well as real time qRT-PCR expression analysis was performed which helped in identification of several CarC3H members that expressed preferentially in specific chickpea tissues as well as during abiotic stresses (desiccation, cold, salinity). Moreover, molecular characterization of an important member CarC3H45 was carried out. This study provides comprehensive genomic information about the important CCCH zinc finger gene family in chickpea. The identified tissue specific and abiotic stress specific CCCH genes could be potential candidates for further characterization to delineate their functional roles in development and stress.

  14. Gut Microbiota-brain Axis

    Institute of Scientific and Technical Information of China (English)

    Hong-Xing Wang; Yu-Ping Wang

    2016-01-01

    Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

  15. A global coupling index of multivariate neural series with application to the evaluation of mild cognitive impairment.

    Science.gov (United States)

    Wen, Dong; Xue, Qing; Lu, Chengbiao; Guan, Xinyong; Wang, Yuping; Li, Xiaoli

    2014-08-01

    Recently, the synchronization between neural signals has been widely used as a key indicator of brain function. To understand comprehensively the effect of synchronization on the brain function, accurate computation of the synchronization strength among multivariate neural series from the whole brain is necessary. In this study, we proposed a method named global coupling index (GCI) to estimate the synchronization strength of multiple neural signals. First of all, performance of the GCI method was evaluated by analyzing simulated EEG signals from a multi-channel neural mass model, including the effects of the frequency band, the coupling coefficient, and the signal noise ratio. Then, the GCI method was applied to analyze the EEG signals from 12 mild cognitive impairment (MCI) subjects and 12 normal controls (NC). The results showed that GCI method had two major advantages over the global synchronization index (GSI) or S-estimator. Firstly, simulation data showed that the GCI method provided both a more robust result on the frequency band and a better performance on the coupling coefficients. Secondly, the actual EEG data demonstrated that GCI method was more sensitive in differentiating the MCI from control subjects, in terms of the global synchronization strength of neural series of specific alpha, beta1 and beta2 frequency bands. Hence, it is suggested that GCI is a better method over GSI and S-estimator to estimate the synchronization strength of multivariate neural series for predicting the MCI from the whole brain EEG recordings. Copyright © 2014. Published by Elsevier Ltd.

  16. Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

    Science.gov (United States)

    Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

    2014-02-01

    Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

  17. Neural precursors of future liking and affective reciprocity.

    Science.gov (United States)

    Zerubavel, Noam; Hoffman, Mark Anthony; Reich, Adam; Ochsner, Kevin N; Bearman, Peter

    2018-04-24

    Why do certain group members end up liking each other more than others? How does affective reciprocity arise in human groups? The prediction of interpersonal sentiment has been a long-standing pursuit in the social sciences. We combined fMRI and longitudinal social network data to test whether newly acquainted group members' reward-related neural responses to images of one another's faces predict their future interpersonal sentiment, even many months later. Specifically, we analyze associations between relationship-specific valuation activity and relationship-specific future liking. We found that one's own future (T2) liking of a particular group member is predicted jointly by actor's initial (T1) neural valuation of partner and by that partner's initial (T1) neural valuation of actor. These actor and partner effects exhibited equivalent predictive strength and were robust when statistically controlling for each other, both individuals' initial liking, and other potential drivers of liking. Behavioral findings indicated that liking was initially unreciprocated at T1 yet became strongly reciprocated by T2. The emergence of affective reciprocity was partly explained by the reciprocal pathways linking dyad members' T1 neural data both to their own and to each other's T2 liking outcomes. These findings elucidate interpersonal brain mechanisms that define how we ultimately end up liking particular interaction partners, how group members' initially idiosyncratic sentiments become reciprocated, and more broadly, how dyads evolve. This study advances a flexible framework for researching the neural foundations of interpersonal sentiments and social relations that-conceptually, methodologically, and statistically-emphasizes group members' neural interdependence. Copyright © 2018 the Author(s). Published by PNAS.

  18. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  19. The Central Neural Foundations of Awareness and Self-Awareness

    Science.gov (United States)

    Pfaff, D.; Martin, E. M.; Weingarten, W.; Vimal, V.

    In the past, neuroscientists have done very well to concentrate onexplaining the mechanisms for very specific, simple behaviors. For example, our laboratory's work with molecular and neural mechanisms of a simple sex behavior proved for the first time that specific biochemical reactions in specific parts of the brain govern a specific behavior [D. W. Pfaff, Drive: Neurobiological and Molecular Mechanisms of Sexual Motivation (The MIT Press, Cambridge, 1999)]. Now, advances in our field coupled with new techniques permit us to attack the problems of explaining global changes of state in the central nervous system. For example, how does a simple sex behavior depend on sexual arousal, and in turn, how does that sexual arousal depend on other forms of CNS arousal? Of surpassing interest is the explanation of the primary causes of brain arousal [D. W. Pfaff, textit{Brain Arousal and Information Theory: Neural and Genetic Mechanisms} (Harvard University Press, Cambridg e, 2006)]. We have hypothesized that the earliest and most elementary event in waking up the brain is the activation of certain primitive nerve cells in the hindbrain reticular formation. Hypothesizing a `generalized arousal' force emanating from these cells puts forth an idea roughly analogous to the hypothesis of a `big bang' in astrophysics, or to our ideas about the magma of the earth in geophysics. Following the activation of this primitive arousal force we are able to be alert and aware. The neuroanatomical pathways serving brain arousal are fairly well known: they are Bilateral, Bidirectional, Universal among vertebrate animals including humans, and they are always involved in Response Potentiation, approach or avoidance responses (BBURP theory). More than 120 genes are involved in the regulation of brain arousal. In theoretical terms, the discussion so far has dealt with `bottoms up' approaches to awareness -- from mechanisms in the hindbrain working through several phylogenetically ancient

  20. Assessment of functional recovery after autologous implantation of neural progenitor cells for the treatment of traumatic brain injury

    International Nuclear Information System (INIS)

    Wu Xing; Zhang Dong; Zuo Zhuantao; Ge Feng; Zhu Jianhong; Zhou Liangfu

    2005-01-01

    Objective: To assess the functional recovery in the patients with traumatic brain injury (TBI) after autologous implantation of neural progenitor cells, and 7 counterparts with matched age, injury location and extent were chosen as the control. Methods: Neural progenitor cells were isolated from exposed brain tissue and propagated for 25 to 30 d, then implanted the autologous neural progenitor cells at seven points around the traumatic regions with MRI-stereotactic guiding device for 7 patients. All recruited patients underwent 18 F-fluorodeox-yglucose (FDG) PET imaging, function MRI (fMRI) and assessment of Glasgow outcome scale extended (GOSE) after operation for open brain trauma. The examinations were repeated one month after neural progenitor cell implantation and then repeated every 3 months during follow-up in the first year, and every 6 months in the second year. The same examinations were performed on untreated counterparts at similar intervals for avoiding deviations of spontaneous recovery. The data were analyzed with region of interest (ROI) and statistical parametric mapping (SPM). Results: At the third month of follow-up, mean tracer uptake in the damaged territory in implantation group increased significantly (P 18 F-FDG in the top of precentral gyrus was significantly increased in implantation group, and the metabolism of 18 F-FDG in the frontal lobe was significantly elevated postoperation according to paired SPM analysis. The activation in fMRI maps was seen in the motor cortex since the third month after implantation, whereas no active signals were detected before implantation or in control group. At the 6th month of follow-up, mean score of GOSE in the group of implantation was 6.63±0.52, whereas the mean score was 4.50 ±0.76 in control group (P 18 F-FDG uptake in the injured area was 3 months prior to the elevation of GOSE. Conclusions: The results of the study show that 18 F-FDG PET and fMRI both showed significantly increased neurological

  1. The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour

    NARCIS (Netherlands)

    van der Meulen, A. A. E.; Biber, K.; Lukovac, S.; Balasubramaniyan, V.; den Dunnen, W. F. A.; Boddeke, H. W. G. M.; Mooij, J. J. A.

    2009-01-01

    Aims: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved

  2. Cracking the neural code, treating paralysis and the future of bioelectronic medicine.

    Science.gov (United States)

    Bouton, C

    2017-07-01

    The human nervous system is a vast network carrying not only sensory and movement information, but also information to and from our organs, intimately linking it to our overall health. Scientists and engineers have been working for decades to tap into this network and 'crack the neural code' by decoding neural signals and learning how to 'speak' the language of the nervous system. Progress has been made in developing neural decoding methods to decipher brain activity and bioelectronic technologies to treat rheumatoid arthritis, paralysis, epilepsy and for diagnosing brain-related diseases such as Parkinson's and Alzheimer's disease. In a recent first-in-human study involving paralysis, a paralysed male study participant regained movement in his hand, years after his injury, through the use of a bioelectronic neural bypass. This work combined neural decoding and neurostimulation methods to translate and re-route signals around damaged neural pathways within the central nervous system. By extending these methods to decipher neural messages in the peripheral nervous system, status information from our bodily functions and specific organs could be gained. This, one day, could allow real-time diagnostics to be performed to give us a deeper insight into a patient's condition, or potentially even predict disease or allow early diagnosis. The future of bioelectronic medicine is extremely bright and is wide open as new diagnostic and treatment options are developed for patients around the world. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  3. Zinc in Infection and Inflammation.

    Science.gov (United States)

    Gammoh, Nour Zahi; Rink, Lothar

    2017-06-17

    Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET) formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB), a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

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

    Science.gov (United States)

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

    2015-11-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  6. Examination of neural systems sub-serving facebook "addiction".

    Science.gov (United States)

    Turel, Ofir; He, Qinghua; Xue, Gui; Xiao, Lin; Bechara, Antoine

    2014-12-01

    Because addictive behaviors typically result from violated homeostasis of the impulsive (amygdala-striatal) and inhibitory (prefrontal cortex) brain systems, this study examined whether these systems sub-serve a specific case of technology-related addiction, namely Facebook "addiction." Using a go/no-go paradigm in functional MRI settings, the study examined how these brain systems in 20 Facebook users (M age = 20.3 yr., SD = 1.3, range = 18-23) who completed a Facebook addiction questionnaire, responded to Facebook and less potent (traffic sign) stimuli. The findings indicated that at least at the examined levels of addiction-like symptoms, technology-related "addictions" share some neural features with substance and gambling addictions, but more importantly they also differ from such addictions in their brain etiology and possibly pathogenesis, as related to abnormal functioning of the inhibitory-control brain system.

  7. Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner.

    Science.gov (United States)

    Bollinger, Justin L; Collins, Kaitlyn E; Patel, Rushi; Wellman, Cara L

    2017-01-01

    Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress

  8. Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner

    Science.gov (United States)

    Bollinger, Justin L.; Collins, Kaitlyn E.; Patel, Rushi

    2017-01-01

    Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress

  9. Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain.

    Science.gov (United States)

    Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan

    2016-04-01

    Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. A common neural code for perceived and inferred emotion.

    Science.gov (United States)

    Skerry, Amy E; Saxe, Rebecca

    2014-11-26

    Although the emotions of other people can often be perceived from overt reactions (e.g., facial or vocal expressions), they can also be inferred from situational information in the absence of observable expressions. How does the human brain make use of these diverse forms of evidence to generate a common representation of a target's emotional state? In the present research, we identify neural patterns that correspond to emotions inferred from contextual information and find that these patterns generalize across different cues from which an emotion can be attributed. Specifically, we use functional neuroimaging to measure neural responses to dynamic facial expressions with positive and negative valence and to short animations in which the valence of a character's emotion could be identified only from the situation. Using multivoxel pattern analysis, we test for regions that contain information about the target's emotional state, identifying representations specific to a single stimulus type and representations that generalize across stimulus types. In regions of medial prefrontal cortex (MPFC), a classifier trained to discriminate emotional valence for one stimulus (e.g., animated situations) could successfully discriminate valence for the remaining stimulus (e.g., facial expressions), indicating a representation of valence that abstracts away from perceptual features and generalizes across different forms of evidence. Moreover, in a subregion of MPFC, this neural representation generalized to trials involving subjectively experienced emotional events, suggesting partial overlap in neural responses to attributed and experienced emotions. These data provide a step toward understanding how the brain transforms stimulus-bound inputs into abstract representations of emotion. Copyright © 2014 the authors 0270-6474/14/3315997-12$15.00/0.

  11. Symptomatic zinc deficiency in experimental zinc deprivation.

    OpenAIRE

    Taylor, C M; Goode, H F; Aggett, P J; Bremner, I; Walker, B E; Kelleher, J

    1992-01-01

    An evaluation of indices of poor zinc status was undertaken in five male subjects in whom dietary zinc intake was reduced from 85 mumol d-1 in an initial phase of the study to 14 mumol d-1. One of the subjects developed features consistent with zinc deficiency after receiving the low zinc diet for 12 days. These features included retroauricular acneform macullo-papular lesions on the face, neck, and shoulders and reductions in plasma zinc, red blood cell zinc, neutrophil zinc and plasma alkal...

  12. Nonequilibrium landscape theory of neural networks

    Science.gov (United States)

    Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

    2013-01-01

    The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape–flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments. PMID:24145451

  13. Nonequilibrium landscape theory of neural networks.

    Science.gov (United States)

    Yan, Han; Zhao, Lei; Hu, Liang; Wang, Xidi; Wang, Erkang; Wang, Jin

    2013-11-05

    The brain map project aims to map out the neuron connections of the human brain. Even with all of the wirings mapped out, the global and physical understandings of the function and behavior are still challenging. Hopfield quantified the learning and memory process of symmetrically connected neural networks globally through equilibrium energy. The energy basins of attractions represent memories, and the memory retrieval dynamics is determined by the energy gradient. However, the realistic neural networks are asymmetrically connected, and oscillations cannot emerge from symmetric neural networks. Here, we developed a nonequilibrium landscape-flux theory for realistic asymmetrically connected neural networks. We uncovered the underlying potential landscape and the associated Lyapunov function for quantifying the global stability and function. We found the dynamics and oscillations in human brains responsible for cognitive processes and physiological rhythm regulations are determined not only by the landscape gradient but also by the flux. We found that the flux is closely related to the degrees of the asymmetric connections in neural networks and is the origin of the neural oscillations. The neural oscillation landscape shows a closed-ring attractor topology. The landscape gradient attracts the network down to the ring. The flux is responsible for coherent oscillations on the ring. We suggest the flux may provide the driving force for associations among memories. We applied our theory to rapid-eye movement sleep cycle. We identified the key regulation factors for function through global sensitivity analysis of landscape topography against wirings, which are in good agreements with experiments.

  14. Towards a magnetoresistive platform for neural signal recording

    Science.gov (United States)

    Sharma, P. P.; Gervasoni, G.; Albisetti, E.; D'Ercoli, F.; Monticelli, M.; Moretti, D.; Forte, N.; Rocchi, A.; Ferrari, G.; Baldelli, P.; Sampietro, M.; Benfenati, F.; Bertacco, R.; Petti, D.

    2017-05-01

    A promising strategy to get deeper insight on brain functionalities relies on the investigation of neural activities at the cellular and sub-cellular level. In this framework, methods for recording neuron electrical activity have gained interest over the years. Main technological challenges are associated to finding highly sensitive detection schemes, providing considerable spatial and temporal resolution. Moreover, the possibility to perform non-invasive assays would constitute a noteworthy benefit. In this work, we present a magnetoresistive platform for the detection of the action potential propagation in neural cells. Such platform allows, in perspective, the in vitro recording of neural signals arising from single neurons, neural networks and brain slices.

  15. Diagnosing Autism Spectrum Disorder from Brain Resting-State Functional Connectivity Patterns Using a Deep Neural Network with a Novel Feature Selection Method.

    Science.gov (United States)

    Guo, Xinyu; Dominick, Kelli C; Minai, Ali A; Li, Hailong; Erickson, Craig A; Lu, Long J

    2017-01-01

    The whole-brain functional connectivity (FC) pattern obtained from resting-state functional magnetic resonance imaging data are commonly applied to study neuropsychiatric conditions such as autism spectrum disorder (ASD) by using different machine learning models. Recent studies indicate that both hyper- and hypo- aberrant ASD-associated FCs were widely distributed throughout the entire brain rather than only in some specific brain regions. Deep neural networks (DNN) with multiple hidden layers have shown the ability to systematically extract lower-to-higher level information from high dimensional data across a series of neural hidden layers, significantly improving classification accuracy for such data. In this study, a DNN with a novel feature selection method (DNN-FS) is developed for the high dimensional whole-brain resting-state FC pattern classification of ASD patients vs. typical development (TD) controls. The feature selection method is able to help the DNN generate low dimensional high-quality representations of the whole-brain FC patterns by selecting features with high discriminating power from multiple trained sparse auto-encoders. For the comparison, a DNN without the feature selection method (DNN-woFS) is developed, and both of them are tested with different architectures (i.e., with different numbers of hidden layers/nodes). Results show that the best classification accuracy of 86.36% is generated by the DNN-FS approach with 3 hidden layers and 150 hidden nodes (3/150). Remarkably, DNN-FS outperforms DNN-woFS for all architectures studied. The most significant accuracy improvement was 9.09% with the 3/150 architecture. The method also outperforms other feature selection methods, e.g., two sample t -test and elastic net. In addition to improving the classification accuracy, a Fisher's score-based biomarker identification method based on the DNN is also developed, and used to identify 32 FCs related to ASD. These FCs come from or cross different pre

  16. Diagnosing Autism Spectrum Disorder from Brain Resting-State Functional Connectivity Patterns Using a Deep Neural Network with a Novel Feature Selection Method

    Directory of Open Access Journals (Sweden)

    Xinyu Guo

    2017-08-01

    Full Text Available The whole-brain functional connectivity (FC pattern obtained from resting-state functional magnetic resonance imaging data are commonly applied to study neuropsychiatric conditions such as autism spectrum disorder (ASD by using different machine learning models. Recent studies indicate that both hyper- and hypo- aberrant ASD-associated FCs were widely distributed throughout the entire brain rather than only in some specific brain regions. Deep neural networks (DNN with multiple hidden layers have shown the ability to systematically extract lower-to-higher level information from high dimensional data across a series of neural hidden layers, significantly improving classification accuracy for such data. In this study, a DNN with a novel feature selection method (DNN-FS is developed for the high dimensional whole-brain resting-state FC pattern classification of ASD patients vs. typical development (TD controls. The feature selection method is able to help the DNN generate low dimensional high-quality representations of the whole-brain FC patterns by selecting features with high discriminating power from multiple trained sparse auto-encoders. For the comparison, a DNN without the feature selection method (DNN-woFS is developed, and both of them are tested with different architectures (i.e., with different numbers of hidden layers/nodes. Results show that the best classification accuracy of 86.36% is generated by the DNN-FS approach with 3 hidden layers and 150 hidden nodes (3/150. Remarkably, DNN-FS outperforms DNN-woFS for all architectures studied. The most significant accuracy improvement was 9.09% with the 3/150 architecture. The method also outperforms other feature selection methods, e.g., two sample t-test and elastic net. In addition to improving the classification accuracy, a Fisher's score-based biomarker identification method based on the DNN is also developed, and used to identify 32 FCs related to ASD. These FCs come from or cross

  17. Leucine-rich repeat-containing synaptic adhesion molecules as organizers of synaptic specificity and diversity.

    Science.gov (United States)

    Schroeder, Anna; de Wit, Joris

    2018-04-09

    The brain harbors billions of neurons that form distinct neural circuits with exquisite specificity. Specific patterns of connectivity between distinct neuronal cell types permit the transfer and computation of information. The molecular correlates that give rise to synaptic specificity are incompletely understood. Recent studies indicate that cell-surface molecules are important determinants of cell type identity and suggest that these are essential players in the specification of synaptic connectivity. Leucine-rich repeat (LRR)-containing adhesion molecules in particular have emerged as key organizers of excitatory and inhibitory synapses. Here, we discuss emerging evidence that LRR proteins regulate the assembly of specific connectivity patterns across neural circuits, and contribute to the diverse structural and functional properties of synapses, two key features that are critical for the proper formation and function of neural circuits.

  18. Creativity, brain, and art: biological and neurological considerations.

    Science.gov (United States)

    Zaidel, Dahlia W

    2014-01-01

    Creativity is commonly thought of as a positive advance for society that transcends the status quo knowledge. Humans display an inordinate capacity for it in a broad range of activities, with art being only one. Most work on creativity's neural substrates measures general creativity, and that is done with laboratory tasks, whereas specific creativity in art is gleaned from acquired brain damage, largely in observing established visual artists, and some in visual de novo artists (became artists after the damage). The verb "to create" has been erroneously equated with creativity; creativity, in the classic sense, does not appear to be enhanced following brain damage, regardless of etiology. The turning to communication through art in lieu of language deficits reflects a biological survival strategy. Creativity in art, and in other domains, is most likely dependent on intact and healthy knowledge and semantic conceptual systems, which are represented in several pathways in the cortex. It is adversely affected when these systems are dysfunctional, for congenital reasons (savant autism) or because of acquired brain damage (stroke, dementia, Parkinson's), whereas inherent artistic talent and skill appear less affected. Clues to the neural substrates of general creativity and specific art creativity can be gleaned from considering that art is produced spontaneously mainly by humans, that there are unique neuroanatomical and neurofunctional organizations in the human brain, and that there are biological antecedents of innovation in animals.

  19. Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (PhosphoProteomic Profiling

    Directory of Open Access Journals (Sweden)

    Ilyas Singec

    2016-09-01

    Full Text Available Controlled differentiation of human embryonic stem cells (hESCs can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs. This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families, phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt.

  20. Cholinergic enhancement of visual attention and neural oscillations in the human brain.

    Science.gov (United States)

    Bauer, Markus; Kluge, Christian; Bach, Dominik; Bradbury, David; Heinze, Hans Jochen; Dolan, Raymond J; Driver, Jon

    2012-03-06

    Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Symmetry Breaking in Space-Time Hierarchies Shapes Brain Dynamics and Behavior.

    Science.gov (United States)

    Pillai, Ajay S; Jirsa, Viktor K

    2017-06-07

    In order to maintain brain function, neural activity needs to be tightly coordinated within the brain network. How this coordination is achieved and related to behavior is largely unknown. It has been previously argued that the study of the link between brain and behavior is impossible without a guiding vision. Here we propose behavioral-level concepts and mechanisms embodied as structured flows on manifold (SFM) that provide a formal description of behavior as a low-dimensional process emerging from a network's dynamics dependent on the symmetry and invariance properties of the network connectivity. Specifically, we demonstrate that the symmetry breaking of network connectivity constitutes a timescale hierarchy resulting in the emergence of an attractive functional subspace. We show that behavior emerges when appropriate conditions imposed upon the couplings are satisfied, justifying the conductance-based nature of synaptic couplings. Our concepts propose design principles for networks predicting how behavior and task rules are represented in real neural circuits and open new avenues for the analyses of neural data. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Normalization as a canonical neural computation

    Science.gov (United States)

    Carandini, Matteo; Heeger, David J.

    2012-01-01

    There is increasing evidence that the brain relies on a set of canonical neural computations, repeating them across brain regions and modalities to apply similar operations to different problems. A promising candidate for such a computation is normalization, in which the responses of neurons are divided by a common factor that typically includes the summed activity of a pool of neurons. Normalization was developed to explain responses in the primary visual cortex and is now thought to operate throughout the visual system, and in many other sensory modalities and brain regions. Normalization may underlie operations such as the representation of odours, the modulatory effects of visual attention, the encoding of value and the integration of multisensory information. Its presence in such a diversity of neural systems in multiple species, from invertebrates to mammals, suggests that it serves as a canonical neural computation. PMID:22108672

  3. Pituitary gland levels of mercury, selenium, iron, and zinc in an Alzheimer`s disease study

    Energy Technology Data Exchange (ETDEWEB)

    Cornett, C.R.; Markesbery, W.R.; Wekstein, D.R.; Ehmann, W.D. [Univ. of Kentucky, Lexington, KY (United States)

    1996-12-31

    Mercury, iron, selenium, and zinc imbalances have been observed in comparisons between Alzheimer`s disease (AD) and control subject brains. Analyses of the pituitary gland have demonstrated that this organ retains relatively high concentrations of trace elements, including mercury, iron, and zinc. Our previous work has shown that the pituitary glands of AD and control subjects are typically higher in these trace elements than brain samples from the same subject. Instrumental neutron activation analysis (INAA) was used to compare the pituitary trace element levels of AD and control subjects. This study also describes the intrasubject relationships of brain trace element levels to those in the pituitary gland of AD and control subjects.

  4. Confused or not Confused?: Disentangling Brain Activity from EEG Data Using Bidirectional LSTM Recurrent Neural Networks.

    Science.gov (United States)

    Ni, Zhaoheng; Yuksel, Ahmet Cem; Ni, Xiuyan; Mandel, Michael I; Xie, Lei

    2017-08-01

    Brain fog, also known as confusion, is one of the main reasons for low performance in the learning process or any kind of daily task that involves and requires thinking. Detecting confusion in a human's mind in real time is a challenging and important task that can be applied to online education, driver fatigue detection and so on. In this paper, we apply Bidirectional LSTM Recurrent Neural Networks to classify students' confusion in watching online course videos from EEG data. The results show that Bidirectional LSTM model achieves the state-of-the-art performance compared with other machine learning approaches, and shows strong robustness as evaluated by cross-validation. We can predict whether or not a student is confused in the accuracy of 73.3%. Furthermore, we find the most important feature to detecting the brain confusion is the gamma 1 wave of EEG signal. Our results suggest that machine learning is a potentially powerful tool to model and understand brain activity.

  5. The Athlete’s Brain: Cross-Sectional Evidence for Neural Efficiency during Cycling Exercise

    Directory of Open Access Journals (Sweden)

    Sebastian Ludyga

    2016-01-01

    Full Text Available The “neural efficiency” hypothesis suggests that experts are characterized by a more efficient cortical function in cognitive tests. Although this hypothesis has been extended to a variety of movement-related tasks within the last years, it is unclear whether or not neural efficiency is present in cyclists performing endurance exercise. Therefore, this study examined brain cortical activity at rest and during exercise between cyclists of higher (HIGH; n=14; 55.6 ± 2.8 mL/min/kg and lower (LOW; n=15; 46.4 ± 4.1 mL/min/kg maximal oxygen consumption (VO2MAX. Male and female participants performed a graded exercise test with spirometry to assess VO2MAX. After 3 to 5 days, EEG was recorded at rest with eyes closed and during cycling at the individual anaerobic threshold over a 30 min period. Possible differences in alpha/beta ratio as well as alpha and beta power were investigated at frontal, central, and parietal sites. The statistical analysis revealed significant differences between groups (F=12.04; p=0.002, as the alpha/beta ratio was increased in HIGH compared to LOW in both the resting state (p≤0.018 and the exercise condition (p≤0.025. The present results indicate enhanced neural efficiency in subjects with high VO2MAX, possibly due to the inhibition of task-irrelevant cognitive processes.

  6. Speaking Two Languages Enhances an Auditory but Not a Visual Neural Marker of Cognitive Inhibition

    Directory of Open Access Journals (Sweden)

    Mercedes Fernandez

    2014-09-01

    Full Text Available The purpose of the present study was to replicate and extend our original findings of enhanced neural inhibitory control in bilinguals. We compared English monolinguals to Spanish/English bilinguals on a non-linguistic, auditory Go/NoGo task while recording event-related brain potentials. New to this study was the visual Go/NoGo task, which we included to investigate whether enhanced neural inhibition in bilinguals extends from the auditory to the visual modality. Results confirmed our original findings and revealed greater inhibition in bilinguals compared to monolinguals. As predicted, compared to monolinguals, bilinguals showed increased N2 amplitude during the auditory NoGo trials, which required inhibitory control, but no differences during the Go trials, which required a behavioral response and no inhibition. Interestingly, during the visual Go/NoGo task, event related brain potentials did not distinguish the two groups, and behavioral responses were similar between the groups regardless of task modality. Thus, only auditory trials that required inhibitory control revealed between-group differences indicative of greater neural inhibition in bilinguals. These results show that experience-dependent neural changes associated with bilingualism are specific to the auditory modality and that the N2 event-related brain potential is a sensitive marker of this plasticity.

  7. The Neural Basis of Changing Social Norms through Persuasion.

    Science.gov (United States)

    Yomogida, Yukihito; Matsumoto, Madoka; Aoki, Ryuta; Sugiura, Ayaka; Phillips, Adam N; Matsumoto, Kenji

    2017-11-24

    Social norms regulate behavior, and changes in norms have a great impact on society. In most modern societies, norms change through interpersonal communication and persuasive messages found in media. Here, we examined the neural basis of persuasion-induced changes in attitude toward and away from norms using fMRI. We measured brain activity while human participants were exposed to persuasive messages directed toward specific norms. Persuasion directed toward social norms specifically activated a set of brain regions including temporal poles, temporo-parietal junction, and medial prefrontal cortex. Beyond these regions, when successful, persuasion away from an accepted norm specifically recruited the left middle temporal and supramarginal gyri. Furthermore, in combination with data from a separate attitude-rating task, we found that left supramarginal gyrus activity represented participant attitude toward norms and tracked the persuasion-induced attitude changes that were away from agreement.

  8. A foldable electrode array for 3D recording of deep-seated abnormal brain cavities

    Science.gov (United States)

    Kil, Dries; De Vloo, Philippe; Fierens, Guy; Ceyssens, Frederik; Hunyadi, Borbála; Bertrand, Alexander; Nuttin, Bart; Puers, Robert

    2018-06-01

    Objective. This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. Approach. A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. Main results. Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. Significance. The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.

  9. Complexity and competition in appetitive and aversive neural circuits

    Directory of Open Access Journals (Sweden)

    Crista L. Barberini

    2012-11-01

    Full Text Available Decision-making often involves using sensory cues to predict possible rewarding or punishing reinforcement outcomes before selecting a course of action. Recent work has revealed complexity in how the brain learns to predict rewards and punishments. Analysis of neural signaling during and after learning in the amygdala and orbitofrontal cortex, two brain areas that process appetitive and aversive stimuli, reveals a dynamic relationship between appetitive and aversive circuits. Specifically, the relationship between signaling in appetitive and aversive circuits in these areas shifts as a function of learning. Furthermore, although appetitive and aversive circuits may often drive opposite behaviors – approaching or avoiding reinforcement depending upon its valence – these circuits can also drive similar behaviors, such as enhanced arousal or attention; these processes also may influence choice behavior. These data highlight the formidable challenges ahead in dissecting how appetitive and aversive neural circuits interact to produce a complex and nuanced range of behaviors.

  10. Regional difference of radiosensitivity of neural cells in the fetal brain of mice on day 13 of gestation

    International Nuclear Information System (INIS)

    Hoshino, Kiyoshi; Kameyama, Yoshiro

    1986-01-01

    Pregnant Slc: ICR mice were exposed to a single whole-body X-irradiation at a dose of 12.5 R or 25 R on day 13 of gestation. After irradiation, fetuses were obtained from mothers at 1- or 3-hour intervals and coronal histological sections were made. Pyknotic cells were counted in the ventricular zone of brain mantle, hippocampal anlage and olfactory bulb. In the 25 R group, peak incidences of pyknotic cells in brain mantle, hippocampal anlage and olfactory bulb were 13.2 %, 6.9 % and 2.2 %, respectively. In the 12.5 R group, these were 6.0 %, 3.2 % and 1.7 %, respectively. This result indicates that neural cells in the ventricular zone of brain mantle are the most radiosensitive among the cerebral regions examined in day-13 mouse fetuses. (author)

  11. The transcription factor Nerfin-1 prevents reversion of neurons into neural stem cells.

    Science.gov (United States)

    Froldi, Francesca; Szuperak, Milan; Weng, Chen-Fang; Shi, Wei; Papenfuss, Anthony T; Cheng, Louise Y

    2015-01-15

    Cellular dedifferentiation is the regression of a cell from a specialized state to a more multipotent state and is implicated in cancer. However, the transcriptional network that prevents differentiated cells from reacquiring stem cell fate is so far unclear. Neuroblasts (NBs), the Drosophila neural stem cells, are a model for the regulation of stem cell self-renewal and differentiation. Here we show that the Drosophila zinc finger transcription factor Nervous fingers 1 (Nerfin-1) locks neurons into differentiation, preventing their reversion into NBs. Following Prospero-dependent neuronal specification in the ganglion mother cell (GMC), a Nerfin-1-specific transcriptional program maintains differentiation in the post-mitotic neurons. The loss of Nerfin-1 causes reversion to multipotency and results in tumors in several neural lineages. Both the onset and rate of neuronal dedifferentiation in nerfin-1 mutant lineages are dependent on Myc- and target of rapamycin (Tor)-mediated cellular growth. In addition, Nerfin-1 is required for NB differentiation at the end of neurogenesis. RNA sequencing (RNA-seq) and chromatin immunoprecipitation (ChIP) analysis show that Nerfin-1 administers its function by repression of self-renewing-specific and activation of differentiation-specific genes. Our findings support the model of bidirectional interconvertibility between neural stem cells and their post-mitotic progeny and highlight the importance of the Nerfin-1-regulated transcriptional program in neuronal maintenance. © 2015 Froldi et al.; Published by Cold Spring Harbor Laboratory Press.

  12. A novel three-dimensional system to study interactions between endothelial cells and neural cells of the developing central nervous system

    Directory of Open Access Journals (Sweden)

    Milner Richard

    2007-01-01

    Full Text Available Abstract Background During angiogenesis in the developing central nervous system (CNS, endothelial cells (EC detach from blood vessels growing on the brain surface, and migrate into the expanding brain parenchyma. Brain angiogenesis is regulated by growth factors and extracellular matrix (ECM proteins secreted by cells of the developing CNS. In addition, recent evidence suggests that EC play an important role in establishing the neural stem cell (NSC niche. Therefore, two-way communication between EC and neural cells is of fundamental importance in the developing CNS. To study the interactions between brain EC and neural cells of the developing CNS, a novel three-dimensional (3-D murine co-culture system was developed. Fluorescent-labelled brain EC were seeded onto neurospheres; floating cellular aggregates that contain NSC/neural precursor cells (NPC and smaller numbers of differentiated cells. Using this system, brain EC attachment, survival and migration into neurospheres was evaluated and the role of integrins in mediating the early adhesive events addressed. Results Brain EC attached, survived and migrated deep into neurospheres over a 5-day period. Neurospheres express the ECM proteins fibronectin and laminin, and brain EC adhesion to neurospheres was inhibited by RGD peptides and antibodies specific for the β1, but not the α6 integrin subunit. Conclusion A novel 3-D co-culture system for analysing the interactions between EC and neural cells of the developing CNS is presented. This system could be used to investigate the reciprocal influence of EC and NSC/NPC; to examine how NSC/NPC influence cerebral angiogenesis, and conversely, to examine how EC regulate the maintenance and differentiation of NSC/NPC. Using this system it is demonstrated that EC attachment to neurospheres is mediated by the fibronectin receptor, α5β1 integrin.

  13. Neonatal brain hemorrhage (NBH) of prematurity: translational mechanisms of the vascular-neural network.

    Science.gov (United States)

    Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R; Rolland, William B; Tang, Jiping; Zhang, John H

    2015-01-01

    Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as posthemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the posthemorrhagic hydrocephalus affecting this vulnerable infant population.

  14. Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network

    Science.gov (United States)

    Lekic, Tim; Klebe, Damon; Poblete, Roy; Krafft, Paul R.; Rolland, William B.; Tang, Jiping; Zhang, John H.

    2015-01-01

    Neonatal brain hemorrhage (NBH) of prematurity is an unfortunate consequence of preterm birth. Complications result in shunt dependence and long-term structural changes such as post-hemorrhagic hydrocephalus, periventricular leukomalacia, gliosis, and neurological dysfunction. Several animal models are available to study this condition, and many basic mechanisms, etiological factors, and outcome consequences, are becoming understood. NBH is an important clinical condition, of which treatment may potentially circumvent shunt complication, and improve functional recovery (cerebral palsy, and cognitive impairments). This review highlights key pathophysiological findings of the neonatal vascular-neural network in the context of molecular mechanisms targeting the post-hemorrhagic hydrocephalus affecting this vulnerable infant population. PMID:25620100

  15. Validation of artificial neural network models for predicting biochemical markers associated with male infertility.

    Science.gov (United States)

    Vickram, A S; Kamini, A Rao; Das, Raja; Pathy, M Ramesh; Parameswari, R; Archana, K; Sridharan, T B

    2016-08-01

    Seminal fluid is the secretion from many glands comprised of several organic and inorganic compounds including free amino acids, proteins, fructose, glucosidase, zinc, and other scavenging elements like Mg(2+), Ca(2+), K(+), and Na(+). Therefore, in the view of development of novel approaches and proper diagnosis to male infertility, overall understanding of the biochemical and molecular composition and its role in regulation of sperm quality is highly desirable. Perhaps this can be achieved through artificial intelligence. This study was aimed to elucidate and predict various biochemical markers present in human seminal plasma with three different neural network models. A total of 177 semen samples were collected for this research (both fertile and infertile samples) and immediately processed to prepare a semen analysis report, based on the protocol of the World Health Organization (WHO [2010]). The semen samples were then categorized into oligoasthenospermia (n=35), asthenospermia (n=35), azoospermia (n=22), normospermia (n=34), oligospermia (n=34), and control (n=17). The major biochemical parameters like total protein content, fructose, glucosidase, and zinc content were elucidated by standard protocols. All the biochemical markers were predicted by using three different artificial neural network (ANN) models with semen parameters as inputs. Of the three models, the back propagation neural network model (BPNN) yielded the best results with mean absolute error 0.025, -0.080, 0.166, and -0.057 for protein, fructose, glucosidase, and zinc, respectively. This suggests that BPNN can be used to predict biochemical parameters for the proper diagnosis of male infertility in assisted reproductive technology (ART) centres. AAS: absorption spectroscopy; AI: artificial intelligence; ANN: artificial neural networks; ART: assisted reproductive technology; BPNN: back propagation neural network model; DT: decision tress; MLP: multilayer perceptron; PESA: percutaneous

  16. Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain.

    Science.gov (United States)

    Emborg, Marina E; Liu, Yan; Xi, Jiajie; Zhang, Xiaoqing; Yin, Yingnan; Lu, Jianfeng; Joers, Valerie; Swanson, Christine; Holden, James E; Zhang, Su-Chun

    2013-03-28

    The generation of induced pluripotent stem cells (iPSCs) opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Method of image segmentation using a neural network. Application to MR imaging of brain tumors

    International Nuclear Information System (INIS)

    Engler, E.; Gautherie, M.

    1992-01-01

    An original method of numerical images segmentation has been developed. This method is based on pixel clustering using a formal neural network configurated by supervised learning of pre-classified examples. The method has been applied to series of MR images of brain tumors (gliomas) with a view to proceed with a 3D-extraction of the tumor volume. This study is part of a project on cancer thermotherapy including the development of a scan-focused ultrasound system of tumor heating and a 3D-numerical thermal model

  18. Zinc

    Science.gov (United States)

    ... Consumer Datos en español Health Professional Other Resources Zinc Fact Sheet for Consumers Have a question? Ask ... find out more about zinc? Disclaimer What is zinc and what does it do? Zinc is a ...

  19. Traffic pollution exposure is associated with altered brain connectivity in school children.

    Science.gov (United States)

    Pujol, Jesus; Martínez-Vilavella, Gerard; Macià, Dídac; Fenoll, Raquel; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Blanco-Hinojo, Laura; Capellades, Jaume; Querol, Xavier; Deus, Joan; Sunyer, Jordi

    2016-04-01

    Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Neuropsychology of humor: an introduction. Part II. Humor and the brain.

    Science.gov (United States)

    Derouesné, Christian

    2016-09-01

    Impairment of the perception or comprehension of humor is observed in patients with focal brain lesions in both hemispheres, but mainly in the right frontal lobe. Studies by functional magnetic resonance imaging in healthy subjects show that humor is associated with activation of two main neural systems in both hemispheres. The detection and resolution of incongruity, cognitive groundings of humor, are associated with activation of the medial prefrontal and temporoparietal cortex, and the humor appreciation with activation of the orbito-frontal and insular cortex, amygdala and the brain reward system. However, activation of these areas is not humor-specific and can be observed in various cognitive or emotional processes. Event-related potential studies confirm the involvement of both hemispheres in humor processing, and suggest that left prefrontal area is associated with joke comprehension and right prefrontal area with the resolution stage. Humor thus appears to be a complex and dynamic functional process involving, on one hand, two specialized but not specific neural systems linked to humor apprehension and appreciation, and, on the other hand, multiple interconnected functional brain networks including neural patterns underlying the moral framework and belief system, acquired by conditioning or imitation during the cognitive development and social interactions of the individual, and more distributed systems associated with the analysis of the current context of humor occurrence. Disturbances of the sense of humor could then result from focal brain alterations localized in one or two of the specialized areas underlying the comprehension or appreciation of humor, or from perturbations of the network interconnectivity in non-focal brain disorders such as Alzheimer's disease or schizophrenia.

  1. Review of Specifications for Zinc-Rich Paints,

    Science.gov (United States)

    1979-09-01

    inspected in 1976, the repair inorganic zinc was in very poor condition due to extensive " chicken pox " rusting. The original red lead alkyd and basic...Nebraska H-186 New Hampshire H-188 New Jersey H-189 /y’/9 7’ 𔃼 New Mexico H(-216.0 North Carolina H-217 North Dakota l1- 246 Ohio H-247 Oklahoma H-254...8217l.% 2. Olharfing I r A1 1 1e a £I )II d To be separately packaged in multiples of 0 54 pound of pox der per M . Cnpost vehicle. One 2.70 pound

  2. Neural correlates of consciousness

    African Journals Online (AJOL)

    neural cells.1 Under this approach, consciousness is believed to be a product of the ... possible only when the 40 Hz electrical hum is sustained among the brain circuits, ... expect the brain stem ascending reticular activating system. (ARAS) and the ... related synchrony of cortical neurons.11 Indeed, stimulation of brainstem ...

  3. Classification of brain MRI with big data and deep 3D convolutional neural networks

    Science.gov (United States)

    Wegmayr, Viktor; Aitharaju, Sai; Buhmann, Joachim

    2018-02-01

    Our ever-aging society faces the growing problem of neurodegenerative diseases, in particular dementia. Magnetic Resonance Imaging provides a unique tool for non-invasive investigation of these brain diseases. However, it is extremely difficult for neurologists to identify complex disease patterns from large amounts of three-dimensional images. In contrast, machine learning excels at automatic pattern recognition from large amounts of data. In particular, deep learning has achieved impressive results in image classification. Unfortunately, its application to medical image classification remains difficult. We consider two reasons for this difficulty: First, volumetric medical image data is considerably scarcer than natural images. Second, the complexity of 3D medical images is much higher compared to common 2D images. To address the problem of small data set size, we assemble the largest dataset ever used for training a deep 3D convolutional neural network to classify brain images as healthy (HC), mild cognitive impairment (MCI) or Alzheimers disease (AD). We use more than 20.000 images from subjects of these three classes, which is almost 9x the size of the previously largest data set. The problem of high dimensionality is addressed by using a deep 3D convolutional neural network, which is state-of-the-art in large-scale image classification. We exploit its ability to process the images directly, only with standard preprocessing, but without the need for elaborate feature engineering. Compared to other work, our workflow is considerably simpler, which increases clinical applicability. Accuracy is measured on the ADNI+AIBL data sets, and the independent CADDementia benchmark.

  4. The neural signatures of distinct psychopathic traits.

    Science.gov (United States)

    Carré, Justin M; Hyde, Luke W; Neumann, Craig S; Viding, Essi; Hariri, Ahmad R

    2013-01-01

    Recent studies suggest that psychopathy may be associated with dysfunction in the neural circuitry supporting both threat- and reward-related processes. However, these studies have involved small samples and often focused on extreme groups. Thus, it is unclear to what extent current findings may generalize to psychopathic traits in the general population. Furthermore, no studies have systematically and simultaneously assessed associations between distinct psychopathy facets and both threat- and reward-related brain function in the same sample of participants. Here, we examined the relationship between threat-related amygdala reactivity and reward-related ventral striatum (VS) reactivity and variation in four facets of self-reported psychopathy in a sample of 200 young adults. Path models indicated that amygdala reactivity to fearful facial expressions is negatively associated with the interpersonal facet of psychopathy, whereas amygdala reactivity to angry facial expressions is positively associated with the lifestyle facet. Furthermore, these models revealed that differential VS reactivity to positive versus negative feedback is negatively associated with the lifestyle facet. There was suggestive evidence for gender-specific patterns of association between brain function and psychopathy facets. Our findings are the first to document differential associations between both threat- and reward-related neural processes and distinct facets of psychopathy and thus provide a more comprehensive picture of the pattern of neural vulnerabilities that may predispose to maladaptive outcomes associated with psychopathy.

  5. Zinc in Infection and Inflammation

    Directory of Open Access Journals (Sweden)

    Nour Zahi Gammoh

    2017-06-01

    Full Text Available Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps (NET formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors of differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B (NF-κB, a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

  6. Compensatory recruitment of neural resources in chronic alcoholism.

    Science.gov (United States)

    Chanraud, Sandra; Sullivan, Edith V

    2014-01-01

    Functional recovery occurs with sustained sobriety, but the neural mechanisms enabling recovery are only now emerging. Theories about promising mechanisms involve concepts of neuroadaptation, where excessive alcohol consumption results in untoward structural and functional brain changes which are subsequently candidates for reversal with sobriety. Views on functional adaptation in chronic alcoholism have expanded with results from neuroimaging studies. Here, we first describe and define the concept of neuroadaptation according to emerging theories based on the growing literature in aging-related cognitive functioning. Then we describe findings as they apply to chronic alcoholism and factors that could influence compensation, such as functional brain reserve and the integrity of brain structure. Finally, we review brain plasticity based on physiologic mechanisms that could underlie mechanisms of neural compensation. Where possible, we provide operational criteria to define functional and neural compensation. © 2014 Elsevier B.V. All rights reserved.

  7. Social Outcomes in Childhood Brain Disorder: A Heuristic Integration of Social Neuroscience and Developmental Psychology

    Science.gov (United States)

    Yeates, Keith Owen; Bigler, Erin D.; Dennis, Maureen; Gerhardt, Cynthia A.; Rubin, Kenneth H.; Stancin, Terry; Taylor, H. Gerry; Vannatta, Kathryn

    2010-01-01

    The authors propose a heuristic model of the social outcomes of childhood brain disorder that draws on models and methods from both the emerging field of social cognitive neuroscience and the study of social competence in developmental psychology/psychopathology. The heuristic model characterizes the relationships between social adjustment, peer interactions and relationships, social problem solving and communication, social-affective and cognitive-executive processes, and their neural substrates. The model is illustrated by research on a specific form of childhood brain disorder, traumatic brain injury. The heuristic model may promote research regarding the neural and cognitive-affective substrates of children’s social development. It also may engender more precise methods of measuring impairments and disabilities in children with brain disorder and suggest ways to promote their social adaptation. PMID:17469991

  8. Prediction of DNA-binding specificity in zinc finger proteins

    Indian Academy of Sciences (India)

    2012-06-25

    Jun 25, 2012 ... Support Vector Machine (SVM) is a state-of-the-art classifica- tion technique. Using canonical binding model, the C2H2 zinc finger protein–DNA interaction interface is modelled by the pairwise amino acid–base interactions. Using a classification framework, known examples of non-binding ZF–DNA pairs.

  9. Neural correlates of naturalistic social cognition: brain-behavior relationships in healthy adults.

    Science.gov (United States)

    Deuse, L; Rademacher, L M; Winkler, L; Schultz, R T; Gründer, G; Lammertz, S E

    2016-11-01

    Being able to infer the thoughts, feelings and intentions of those around us is indispensable in order to function in a social world. Despite growing interest in social cognition and its neural underpinnings, the factors that contribute to successful mental state attribution remain unclear. Current knowledge is limited because the most widely used tasks suffer from two main constraints: (i) They fail to capture individual variability due to ceiling effects and (ii) they use highly simplistic, often artificial stimuli inapt to mirror real-world socio-cognitive demands. In the present study, we address these problems by employing complex depictions of naturalistic social interactions that vary in both valence (positive vs negative) and ambiguity (high vs low). Thirty-eight healthy participants (20 female) made mental state judgments while brain responses were obtained using functional magnetic resonance imaging (fMRI). Accuracy varied based on valence and ambiguity conditions and women were more accurate than men with highly ambiguous social stimuli. Activity of the orbitofrontal cortex predicted performance in the high ambiguity condition. The results shed light on subtle differences in mentalizing abilities and associated neural activity. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  10. Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate.

    Science.gov (United States)

    Moon, Mi-Young; Kim, Hyun Jung; Choi, Bo Young; Sohn, Min; Chung, Tae Nyoung; Suh, Sang Won

    2018-01-01

    Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs) are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage. AD-MSCs showed high proliferation rates on day 6 in 30  μ M and 100  μ M of ZnCl 2 . Zinc chelation inhibited AD-MSC proliferation via downregulation of ERK1/2 activity. We then assessed whether zinc was involved in cell migration and neurite outgrowth during differentiation. After three days of neuronal differentiation, TUJ-1-positive cells were observed, implying that AD-MSCs had differentiated into early neuron or neuron-like cells. Neurite outgrowth was increased in the zinc-treated group, while the CaEDTA-treated group showed diminished, shrunken neurites. Furthermore, we showed that zinc promoted neurite outgrowth via the inactivation of RhoA and led to the induction of neuronal gene expression (MAP2 and nestin) in differentiated stem cells. Taken together, zinc promoted AD-MSC proliferation and affected neuronal differentiation, mainly by increasing neurite outgrowth.

  11. Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate

    Directory of Open Access Journals (Sweden)

    Mi-Young Moon

    2018-01-01

    Full Text Available Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage. AD-MSCs showed high proliferation rates on day 6 in 30 μM and 100 μM of ZnCl2. Zinc chelation inhibited AD-MSC proliferation via downregulation of ERK1/2 activity. We then assessed whether zinc was involved in cell migration and neurite outgrowth during differentiation. After three days of neuronal differentiation, TUJ-1-positive cells were observed, implying that AD-MSCs had differentiated into early neuron or neuron-like cells. Neurite outgrowth was increased in the zinc-treated group, while the CaEDTA-treated group showed diminished, shrunken neurites. Furthermore, we showed that zinc promoted neurite outgrowth via the inactivation of RhoA and led to the induction of neuronal gene expression (MAP2 and nestin in differentiated stem cells. Taken together, zinc promoted AD-MSC proliferation and affected neuronal differentiation, mainly by increasing neurite outgrowth.

  12. Influence of neural adaptation on dynamics and equilibrium state of neural activities in a ring neural network

    Science.gov (United States)

    Takiyama, Ken

    2017-12-01

    How neural adaptation affects neural information processing (i.e. the dynamics and equilibrium state of neural activities) is a central question in computational neuroscience. In my previous works, I analytically clarified the dynamics and equilibrium state of neural activities in a ring-type neural network model that is widely used to model the visual cortex, motor cortex, and several other brain regions. The neural dynamics and the equilibrium state in the neural network model corresponded to a Bayesian computation and statistically optimal multiple information integration, respectively, under a biologically inspired condition. These results were revealed in an analytically tractable manner; however, adaptation effects were not considered. Here, I analytically reveal how the dynamics and equilibrium state of neural activities in a ring neural network are influenced by spike-frequency adaptation (SFA). SFA is an adaptation that causes gradual inhibition of neural activity when a sustained stimulus is applied, and the strength of this inhibition depends on neural activities. I reveal that SFA plays three roles: (1) SFA amplifies the influence of external input in neural dynamics; (2) SFA allows the history of the external input to affect neural dynamics; and (3) the equilibrium state corresponds to the statistically optimal multiple information integration independent of the existence of SFA. In addition, the equilibrium state in a ring neural network model corresponds to the statistically optimal integration of multiple information sources under biologically inspired conditions, independent of the existence of SFA.

  13. Fetal brain extracellular matrix boosts neuronal network formation in 3D bioengineered model of cortical brain tissue.

    Science.gov (United States)

    Sood, Disha; Chwalek, Karolina; Stuntz, Emily; Pouli, Dimitra; Du, Chuang; Tang-Schomer, Min; Georgakoudi, Irene; Black, Lauren D; Kaplan, David L

    2016-01-01

    The extracellular matrix (ECM) constituting up to 20% of the organ volume is a significant component of the brain due to its instructive role in the compartmentalization of functional microdomains in every brain structure. The composition, quantity and structure of ECM changes dramatically during the development of an organism greatly contributing to the remarkably sophisticated architecture and function of the brain. Since fetal brain is highly plastic, we hypothesize that the fetal brain ECM may contain cues promoting neural growth and differentiation, highly desired in regenerative medicine. Thus, we studied the effect of brain-derived fetal and adult ECM complemented with matricellular proteins on cortical neurons using in vitro 3D bioengineered model of cortical brain tissue. The tested parameters included neuronal network density, cell viability, calcium signaling and electrophysiology. Both, adult and fetal brain ECM as well as matricellular proteins significantly improved neural network formation as compared to single component, collagen I matrix. Additionally, the brain ECM improved cell viability and lowered glutamate release. The fetal brain ECM induced superior neural network formation, calcium signaling and spontaneous spiking activity over adult brain ECM. This study highlights the difference in the neuroinductive properties of fetal and adult brain ECM and suggests that delineating the basis for this divergence may have implications for regenerative medicine.

  14. High-throughput dual-color precision imaging for brain-wide mapping of the connectome with cytoarchitectonic landmarks at the cellular level (Conference Presentation)

    Science.gov (United States)

    Luo, Qingming; Gong, Hui; Yuan, Jing; Li, Xiangning; Li, Anan; Xu, Tonghui

    2017-02-01

    Deciphering the fine morphology and precise location of neurons and neural circuits are crucial to enhance our understanding of brain function and diseases. Traditionally, we have to map brain images to coarse axial-sampling planar reference atlases to orient neural structures. However, this means might fail to orient neural projections at single-cell resolution due to position errors resulting from individual differences at the cellular level. Here, we present a high-throughput imaging method that can automatically obtain the fine morphologies and precise locations of both neurons and circuits, employing wide-field large-volume tomography to acquire three-dimensional images of thick tissue and implementing real-time soma counterstaining to obtain cytoarchitectonic landmarks during the imaging process. The reconstruction and orientation of brain-wide neural circuits at single-neuron resolution can be accomplished for the same mouse brain without additional counterstains or image registration. Using our method, mouse brain imaging datasets of multiple type-specific neurons and circuits were successfully acquired, demonstrating the versatility. The results show that the simultaneous acquisition of labeled neural structures and cytoarchitecture reference at single-neuron resolution in the same brain greatly facilitates precise tracing of long-range projections and accurate locating of nuclei. Our method provides a novel and effective tool for application in studies on genetic dissection, brain function and the pathology of the nervous system.

  15. Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.

    Science.gov (United States)

    Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji

    2016-05-01

    Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

  16. Improving Neural Recording Technology at the Nanoscale

    Science.gov (United States)

    Ferguson, John Eric

    Neural recording electrodes are widely used to study normal brain function (e.g., learning, memory, and sensation) and abnormal brain function (e.g., epilepsy, addiction, and depression) and to interface with the nervous system for neuroprosthetics. With a deep understanding of the electrode interface at the nanoscale and the use of novel nanofabrication processes, neural recording electrodes can be designed that surpass previous limits and enable new applications. In this thesis, I will discuss three projects. In the first project, we created an ultralow-impedance electrode coating by controlling the nanoscale texture of electrode surfaces. In the second project, we developed a novel nanowire electrode for long-term intracellular recordings. In the third project, we created a means of wirelessly communicating with ultra-miniature, implantable neural recording devices. The techniques developed for these projects offer significant improvements in the quality of neural recordings. They can also open the door to new types of experiments and medical devices, which can lead to a better understanding of the brain and can enable novel and improved tools for clinical applications.

  17. The malleable brain: plasticity of neural circuits and behavior - a review from students to students.

    Science.gov (United States)

    Schaefer, Natascha; Rotermund, Carola; Blumrich, Eva-Maria; Lourenco, Mychael V; Joshi, Pooja; Hegemann, Regina U; Jamwal, Sumit; Ali, Nilufar; García Romero, Ezra Michelet; Sharma, Sorabh; Ghosh, Shampa; Sinha, Jitendra K; Loke, Hannah; Jain, Vishal; Lepeta, Katarzyna; Salamian, Ahmad; Sharma, Mahima; Golpich, Mojtaba; Nawrotek, Katarzyna; Paidi, Ramesh K; Shahidzadeh, Sheila M; Piermartiri, Tetsade; Amini, Elham; Pastor, Veronica; Wilson, Yvette; Adeniyi, Philip A; Datusalia, Ashok K; Vafadari, Benham; Saini, Vedangana; Suárez-Pozos, Edna; Kushwah, Neetu; Fontanet, Paula; Turner, Anthony J

    2017-06-20

    One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation and long-term depression, respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by long-term potentiation and long-term depression, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity. Read the Editorial Highlight for this article on doi: 10.1111/jnc.14102. © 2017 International Society for Neurochemistry.

  18. The PennBMBI: Design of a General Purpose Wireless Brain-Machine-Brain Interface System.

    Science.gov (United States)

    Liu, Xilin; Zhang, Milin; Subei, Basheer; Richardson, Andrew G; Lucas, Timothy H; Van der Spiegel, Jan

    2015-04-01

    In this paper, a general purpose wireless Brain-Machine-Brain Interface (BMBI) system is presented. The system integrates four battery-powered wireless devices for the implementation of a closed-loop sensorimotor neural interface, including a neural signal analyzer, a neural stimulator, a body-area sensor node and a graphic user interface implemented on the PC end. The neural signal analyzer features a four channel analog front-end with configurable bandpass filter, gain stage, digitization resolution, and sampling rate. The target frequency band is configurable from EEG to single unit activity. A noise floor of 4.69 μVrms is achieved over a bandwidth from 0.05 Hz to 6 kHz. Digital filtering, neural feature extraction, spike detection, sensing-stimulating modulation, and compressed sensing measurement are realized in a central processing unit integrated in the analyzer. A flash memory card is also integrated in the analyzer. A 2-channel neural stimulator with a compliance voltage up to ± 12 V is included. The stimulator is capable of delivering unipolar or bipolar, charge-balanced current pulses with programmable pulse shape, amplitude, width, pulse train frequency and latency. A multi-functional sensor node, including an accelerometer, a temperature sensor, a flexiforce sensor and a general sensor extension port has been designed. A computer interface is designed to monitor, control and configure all aforementioned devices via a wireless link, according to a custom designed communication protocol. Wireless closed-loop operation between the sensory devices, neural stimulator, and neural signal analyzer can be configured. The proposed system was designed to link two sites in the brain, bridging the brain and external hardware, as well as creating new sensory and motor pathways for clinical practice. Bench test and in vivo experiments are performed to verify the functions and performances of the system.

  19. Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ-aminobutyric acid, and zinc.

    Science.gov (United States)

    Hassel, Bjørnar; Dahlberg, Daniel; Mariussen, Espen; Goverud, Ingeborg Løstegaard; Antal, Ellen-Ann; Tønjum, Tone; Maehlen, Jan

    2014-12-01

    Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12-fold, and at 20 hr it had increased >30-fold. The extracellular level of aspartate and γ-aminobutyric acid (GABA) also increased greatly. Extracellular Zn(2+) , which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1-2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N-methyl-D-aspartate receptor antagonist MK-801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection-related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients. © 2014 Wiley Periodicals, Inc.

  20. An Initial Investigation of the Neural Correlates of Word Processing in Preschoolers With Specific Language Impairment.

    Science.gov (United States)

    Haebig, Eileen; Leonard, Laurence; Usler, Evan; Deevy, Patricia; Weber, Christine

    2018-03-15

    Previous behavioral studies have found deficits in lexical-semantic abilities in children with specific language impairment (SLI), including reduced depth and breadth of word knowledge. This study explored the neural correlates of early emerging familiar word processing in preschoolers with SLI and typical development. Fifteen preschoolers with typical development and 15 preschoolers with SLI were presented with pictures followed after a brief delay by an auditory label that did or did not match. Event-related brain potentials were time locked to the onset of the auditory labels. Children provided verbal judgments of whether the label matched the picture. There were no group differences in the accuracy of identifying when pictures and labels matched or mismatched. Event-related brain potential data revealed that mismatch trials elicited a robust N400 in both groups, with no group differences in mean amplitude or peak latency. However, the typically developing group demonstrated a more robust late positive component, elicited by mismatch trials. These initial findings indicate that lexical-semantic access of early acquired words, indexed by the N400, does not differ between preschoolers with SLI and typical development when highly familiar words are presented in isolation. However, the typically developing group demonstrated a more mature profile of postlexical reanalysis and integration, indexed by an emerging late positive component. The findings lay the necessary groundwork for better understanding processing of newly learned words in children with SLI.