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Sample records for human cortical neural

  1. Generation of human cortical neurons from a new immortal fetal neural stem cell line

    International Nuclear Information System (INIS)

    Cacci, E.; Villa, A.; Parmar, M.; Cavallaro, M.; Mandahl, N.; Lindvall, O.; Martinez-Serrano, A.; Kokaia, Z.

    2007-01-01

    Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology

  2. Individual Movement Variability Magnitudes Are Explained by Cortical Neural Variability.

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    Haar, Shlomi; Donchin, Opher; Dinstein, Ilan

    2017-09-13

    Humans exhibit considerable motor variability even across trivial reaching movements. This variability can be separated into specific kinematic components such as extent and direction that are thought to be governed by distinct neural processes. Here, we report that individual subjects (males and females) exhibit different magnitudes of kinematic variability, which are consistent (within individual) across movements to different targets and regardless of which arm (right or left) was used to perform the movements. Simultaneous fMRI recordings revealed that the same subjects also exhibited different magnitudes of fMRI variability across movements in a variety of motor system areas. These fMRI variability magnitudes were also consistent across movements to different targets when performed with either arm. Cortical fMRI variability in the posterior-parietal cortex of individual subjects explained their movement-extent variability. This relationship was apparent only in posterior-parietal cortex and not in other motor system areas, thereby suggesting that individuals with more variable movement preparation exhibit larger kinematic variability. We therefore propose that neural and kinematic variability are reliable and interrelated individual characteristics that may predispose individual subjects to exhibit distinct motor capabilities. SIGNIFICANCE STATEMENT Neural activity and movement kinematics are remarkably variable. Although intertrial variability is rarely studied, here, we demonstrate that individual human subjects exhibit distinct magnitudes of neural and kinematic variability that are reproducible across movements to different targets and when performing these movements with either arm. Furthermore, when examining the relationship between cortical variability and movement variability, we find that cortical fMRI variability in parietal cortex of individual subjects explained their movement extent variability. This enabled us to explain why some subjects

  3. Neural speech recognition: continuous phoneme decoding using spatiotemporal representations of human cortical activity

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    Moses, David A.; Mesgarani, Nima; Leonard, Matthew K.; Chang, Edward F.

    2016-10-01

    Objective. The superior temporal gyrus (STG) and neighboring brain regions play a key role in human language processing. Previous studies have attempted to reconstruct speech information from brain activity in the STG, but few of them incorporate the probabilistic framework and engineering methodology used in modern speech recognition systems. In this work, we describe the initial efforts toward the design of a neural speech recognition (NSR) system that performs continuous phoneme recognition on English stimuli with arbitrary vocabulary sizes using the high gamma band power of local field potentials in the STG and neighboring cortical areas obtained via electrocorticography. Approach. The system implements a Viterbi decoder that incorporates phoneme likelihood estimates from a linear discriminant analysis model and transition probabilities from an n-gram phonemic language model. Grid searches were used in an attempt to determine optimal parameterizations of the feature vectors and Viterbi decoder. Main results. The performance of the system was significantly improved by using spatiotemporal representations of the neural activity (as opposed to purely spatial representations) and by including language modeling and Viterbi decoding in the NSR system. Significance. These results emphasize the importance of modeling the temporal dynamics of neural responses when analyzing their variations with respect to varying stimuli and demonstrate that speech recognition techniques can be successfully leveraged when decoding speech from neural signals. Guided by the results detailed in this work, further development of the NSR system could have applications in the fields of automatic speech recognition and neural prosthetics.

  4. Cortico-Cortical Receptive Field Estimates in Human Visual Cortex

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    Koen V Haak

    2012-05-01

    Full Text Available Human visual cortex comprises many visual areas that contain a map of the visual field (Wandell et al 2007, Neuron 56, 366–383. These visual field maps can be identified readily in individual subjects with functional magnetic resonance imaging (fMRI during experimental sessions that last less than an hour (Wandell and Winawer 2011, Vis Res 718–737. Hence, visual field mapping with fMRI has been, and still is, a heavily used technique to examine the organisation of both normal and abnormal human visual cortex (Haak et al 2011, ACNR, 11(3, 20–21. However, visual field mapping cannot reveal every aspect of human visual cortex organisation. For example, the information processed within a visual field map arrives from somewhere and is sent to somewhere, and visual field mapping does not derive these input/output relationships. Here, we describe a new, model-based analysis for estimating the dependence between signals in distinct cortical regions using functional magnetic resonance imaging (fMRI data. Just as a stimulus-referred receptive field predicts the neural response as a function of the stimulus contrast, the neural-referred receptive field predicts the neural response as a function of responses elsewhere in the nervous system. When applied to two cortical regions, this function can be called the cortico-cortical receptive field (CCRF. We model the CCRF as a Gaussian-weighted region on the cortical surface and apply the model to data from both stimulus-driven and resting-state experimental conditions in visual cortex.

  5. Using an Artificial Neural Bypass to Restore Cortical Control of Rhythmic Movements in a Human with Quadriplegia

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    Sharma, Gaurav; Friedenberg, David A.; Annetta, Nicholas; Glenn, Bradley; Bockbrader, Marcie; Majstorovic, Connor; Domas, Stephanie; Mysiw, W. Jerry; Rezai, Ali; Bouton, Chad

    2016-09-01

    Neuroprosthetic technology has been used to restore cortical control of discrete (non-rhythmic) hand movements in a paralyzed person. However, cortical control of rhythmic movements which originate in the brain but are coordinated by Central Pattern Generator (CPG) neural networks in the spinal cord has not been demonstrated previously. Here we show a demonstration of an artificial neural bypass technology that decodes cortical activity and emulates spinal cord CPG function allowing volitional rhythmic hand movement. The technology uses a combination of signals recorded from the brain, machine-learning algorithms to decode the signals, a numerical model of CPG network, and a neuromuscular electrical stimulation system to evoke rhythmic movements. Using the neural bypass, a quadriplegic participant was able to initiate, sustain, and switch between rhythmic and discrete finger movements, using his thoughts alone. These results have implications in advancing neuroprosthetic technology to restore complex movements in people living with paralysis.

  6. Human cortical neural correlates of visual fatigue during binocular depth perception: An fNIRS study.

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    Tingting Cai

    Full Text Available Functional near-infrared spectroscopy (fNIRS was adopted to investigate the cortical neural correlates of visual fatigue during binocular depth perception for different disparities (from 0.1° to 1.5°. By using a slow event-related paradigm, the oxyhaemoglobin (HbO responses to fused binocular stimuli presented by the random-dot stereogram (RDS were recorded over the whole visual dorsal area. To extract from an HbO curve the characteristics that are correlated with subjective experiences of stereopsis and visual fatigue, we proposed a novel method to fit the time-course HbO curve with various response functions which could reflect various processes of binocular depth perception. Our results indicate that the parietal-occipital cortices are spatially correlated with binocular depth perception and that the process of depth perception includes two steps, associated with generating and sustaining stereovision. Visual fatigue is caused mainly by generating stereovision, while the amplitude of the haemodynamic response corresponding to sustaining stereovision is correlated with stereopsis. Combining statistical parameter analysis and the fitted time-course analysis, fNIRS could be a promising method to study visual fatigue and possibly other multi-process neural bases.

  7. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

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    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R., E-mail: mundy.william@epa.gov

    2011-11-15

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  8. Comparative sensitivity of human and rat neural cultures to chemical-induced inhibition of neurite outgrowth

    International Nuclear Information System (INIS)

    Harrill, Joshua A.; Freudenrich, Theresa M.; Robinette, Brian L.; Mundy, William R.

    2011-01-01

    There is a need for rapid, efficient and cost-effective alternatives to traditional in vivo developmental neurotoxicity testing. In vitro cell culture models can recapitulate many of the key cellular processes of nervous system development, including neurite outgrowth, and may be used as screening tools to identify potential developmental neurotoxicants. The present study compared primary rat cortical cultures and human embryonic stem cell-derived neural cultures in terms of: 1) reproducibility of high content image analysis based neurite outgrowth measurements, 2) dynamic range of neurite outgrowth measurements and 3) sensitivity to chemicals which have been shown to inhibit neurite outgrowth. There was a large increase in neurite outgrowth between 2 and 24 h in both rat and human cultures. Image analysis data collected across multiple cultures demonstrated that neurite outgrowth measurements in rat cortical cultures were more reproducible and had higher dynamic range as compared to human neural cultures. Human neural cultures were more sensitive than rat cortical cultures to chemicals previously shown to inhibit neurite outgrowth. Parallel analysis of morphological (neurite count, neurite length) and cytotoxicity (neurons per field) measurements were used to detect selective effects on neurite outgrowth. All chemicals which inhibited neurite outgrowth in rat cortical cultures did so at concentrations which did not concurrently affect the number of neurons per field, indicating selective effects on neurite outgrowth. In contrast, more than half the chemicals which inhibited neurite outgrowth in human neural cultures did so at concentrations which concurrently decreased the number of neurons per field, indicating that effects on neurite outgrowth were secondary to cytotoxicity. Overall, these data demonstrate that the culture models performed differently in terms of reproducibility, dynamic range and sensitivity to neurite outgrowth inhibitors. While human neural

  9. Human cortical areas involved in perception of surface glossiness.

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    Wada, Atsushi; Sakano, Yuichi; Ando, Hiroshi

    2014-09-01

    Glossiness is the visual appearance of an object's surface as defined by its surface reflectance properties. Despite its ecological importance, little is known about the neural substrates underlying its perception. In this study, we performed the first human neuroimaging experiments that directly investigated where the processing of glossiness resides in the visual cortex. First, we investigated the cortical regions that were more activated by observing high glossiness compared with low glossiness, where the effects of simple luminance and luminance contrast were dissociated by controlling the illumination conditions (Experiment 1). As cortical regions that may be related to the processing of glossiness, V2, V3, hV4, VO-1, VO-2, collateral sulcus (CoS), LO-1, and V3A/B were identified, which also showed significant correlation with the perceived level of glossiness. This result is consistent with the recent monkey studies that identified selective neural response to glossiness in the ventral visual pathway, except for V3A/B in the dorsal visual pathway, whose involvement in the processing of glossiness could be specific to the human visual system. Second, we investigated the cortical regions that were modulated by selective attention to glossiness (Experiment 2). The visual areas that showed higher activation to attention to glossiness than that to either form or orientation were identified as right hV4, right VO-2, and right V3A/B, which were commonly identified in Experiment 1. The results indicate that these commonly identified visual areas in the human visual cortex may play important roles in glossiness perception. Copyright © 2014. Published by Elsevier Inc.

  10. Interactions between thalamic and cortical rhythms during semantic memory recall in human

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    Slotnick, Scott D.; Moo, Lauren R.; Kraut, Michael A.; Lesser, Ronald P.; Hart, John, Jr.

    2002-04-01

    Human scalp electroencephalographic rhythms, indicative of cortical population synchrony, have long been posited to reflect cognitive processing. Although numerous studies employing simultaneous thalamic and cortical electrode recording in nonhuman animals have explored the role of the thalamus in the modulation of cortical rhythms, direct evidence for thalamocortical modulation in human has not, to our knowledge, been obtained. We simultaneously recorded from thalamic and scalp electrodes in one human during performance of a cognitive task and found a spatially widespread, phase-locked, low-frequency rhythm (7-8 Hz) power decrease at thalamus and scalp during semantic memory recall. This low-frequency rhythm power decrease was followed by a spatially specific, phase-locked, fast-rhythm (21-34 Hz) power increase at thalamus and occipital scalp. Such a pattern of thalamocortical activity reflects a plausible neural mechanism underlying semantic memory recall that may underlie other cognitive processes as well.

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

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    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.

  12. Sharpened cortical tuning and enhanced cortico-cortical communication contribute to the long-term neural mechanisms of visual motion perceptual learning.

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    Chen, Nihong; Bi, Taiyong; Zhou, Tiangang; Li, Sheng; Liu, Zili; Fang, Fang

    2015-07-15

    Much has been debated about whether the neural plasticity mediating perceptual learning takes place at the sensory or decision-making stage in the brain. To investigate this, we trained human subjects in a visual motion direction discrimination task. Behavioral performance and BOLD signals were measured before, immediately after, and two weeks after training. Parallel to subjects' long-lasting behavioral improvement, the neural selectivity in V3A and the effective connectivity from V3A to IPS (intraparietal sulcus, a motion decision-making area) exhibited a persistent increase for the trained direction. Moreover, the improvement was well explained by a linear combination of the selectivity and connectivity increases. These findings suggest that the long-term neural mechanisms of motion perceptual learning are implemented by sharpening cortical tuning to trained stimuli at the sensory processing stage, as well as by optimizing the connections between sensory and decision-making areas in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells

    DEFF Research Database (Denmark)

    Chandrasekaran, Abinaya; Avci, Hasan; Ochalek, Anna

    2017-01-01

    Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency......), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4). Electron microscopy demonstrated that both methods resulted in morphologically similar neural rosettes. However, quantification of NPCs derived from 3D neural induction exhibited an increase in the number of PAX6/NESTIN double positive cells...... the electrophysiological properties between the two induction methods. In conclusion, 3D neural induction increases the yield of PAX6+/NESTIN+ cells and gives rise to neurons with longer neurites, which might be an advantage for the production of forebrain cortical neurons, highlighting the potential of 3D neural...

  14. Degraded attentional modulation of cortical neural populations in strabismic amblyopia.

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    Hou, Chuan; Kim, Yee-Joon; Lai, Xin Jie; Verghese, Preeti

    2016-01-01

    Behavioral studies have reported reduced spatial attention in amblyopia, a developmental disorder of spatial vision. However, the neural populations in the visual cortex linked with these behavioral spatial attention deficits have not been identified. Here, we use functional MRI-informed electroencephalography source imaging to measure the effect of attention on neural population activity in the visual cortex of human adult strabismic amblyopes who were stereoblind. We show that compared with controls, the modulatory effects of selective visual attention on the input from the amblyopic eye are substantially reduced in the primary visual cortex (V1) as well as in extrastriate visual areas hV4 and hMT+. Degraded attentional modulation is also found in the normal-acuity fellow eye in areas hV4 and hMT+ but not in V1. These results provide electrophysiological evidence that abnormal binocular input during a developmental critical period may impact cortical connections between the visual cortex and higher level cortices beyond the known amblyopic losses in V1 and V2, suggesting that a deficit of attentional modulation in the visual cortex is an important component of the functional impairment in amblyopia. Furthermore, we find that degraded attentional modulation in V1 is correlated with the magnitude of interocular suppression and the depth of amblyopia. These results support the view that the visual suppression often seen in strabismic amblyopia might be a form of attentional neglect of the visual input to the amblyopic eye.

  15. On the nature and evolution of the neural bases of human language

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    Lieberman, Philip

    2002-01-01

    The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on

  16. Development and function of human cerebral cortex neural networks from pluripotent stem cells in vitro.

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    Kirwan, Peter; Turner-Bridger, Benita; Peter, Manuel; Momoh, Ayiba; Arambepola, Devika; Robinson, Hugh P C; Livesey, Frederick J

    2015-09-15

    A key aspect of nervous system development, including that of the cerebral cortex, is the formation of higher-order neural networks. Developing neural networks undergo several phases with distinct activity patterns in vivo, which are thought to prune and fine-tune network connectivity. We report here that human pluripotent stem cell (hPSC)-derived cerebral cortex neurons form large-scale networks that reflect those found in the developing cerebral cortex in vivo. Synchronised oscillatory networks develop in a highly stereotyped pattern over several weeks in culture. An initial phase of increasing frequency of oscillations is followed by a phase of decreasing frequency, before giving rise to non-synchronous, ordered activity patterns. hPSC-derived cortical neural networks are excitatory, driven by activation of AMPA- and NMDA-type glutamate receptors, and can undergo NMDA-receptor-mediated plasticity. Investigating single neuron connectivity within PSC-derived cultures, using rabies-based trans-synaptic tracing, we found two broad classes of neuronal connectivity: most neurons have small numbers (40). These data demonstrate that the formation of hPSC-derived cortical networks mimics in vivo cortical network development and function, demonstrating the utility of in vitro systems for mechanistic studies of human forebrain neural network biology. © 2015. Published by The Company of Biologists Ltd.

  17. Gamma Oscillations and Neural Field DCMs Can Reveal Cortical Excitability and Microstructure

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    Dimitris Pinotsis

    2014-05-01

    Full Text Available This paper shows how gamma oscillations can be combined with neural population models and dynamic causal modeling (DCM to distinguish among alternative hypotheses regarding cortical excitability and microstructure. This approach exploits inter-subject variability and trial-specific effects associated with modulations in the peak frequency of gamma oscillations. Neural field models are used to evaluate model evidence and obtain parameter estimates using invasive and non-invasive gamma recordings. Our overview comprises two parts: in the first part, we use neural fields to simulate neural activity and distinguish the effects of post synaptic filtering on predicted responses in terms of synaptic rate constants that correspond to different timescales and distinct neurotransmitters. We focus on model predictions of conductance and convolution based field models and show that these can yield spectral responses that are sensitive to biophysical properties of local cortical circuits like synaptic kinetics and filtering; we also consider two different mechanisms for this filtering: a nonlinear mechanism involving specific conductances and a linear convolution of afferent firing rates producing post synaptic potentials. In the second part of this paper, we use neural fields quantitatively—to fit empirical data recorded during visual stimulation. We present two studies of spectral responses obtained from the visual cortex during visual perception experiments: in the first study, MEG data were acquired during a task designed to show how activity in the gamma band is related to visual perception, while in the second study, we exploited high density electrocorticographic (ECoG data to study the effect of varying stimulus contrast on cortical excitability and gamma peak frequency.

  18. GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation

    Directory of Open Access Journals (Sweden)

    Antonela Bonafina

    2018-03-01

    Full Text Available Summary: The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2, promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors. : In this article, Ledda and colleagues show that GDNF acting through its receptor GFRα1 plays a critical role in the maturation of cortical progenitors by counteracting FGF2 self-renewal activity on neural stem cells and promoting neuronal differentiation. Keywords: GDNF, GFRα1, cortical precursors, proliferation, postmitotic neurons, neuronal differentiation

  19. A neural model of motion processing and visual navigation by cortical area MST.

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    Grossberg, S; Mingolla, E; Pack, C

    1999-12-01

    Cells in the dorsal medial superior temporal cortex (MSTd) process optic flow generated by self-motion during visually guided navigation. A neural model shows how interactions between well-known neural mechanisms (log polar cortical magnification, Gaussian motion-sensitive receptive fields, spatial pooling of motion-sensitive signals and subtractive extraretinal eye movement signals) lead to emergent properties that quantitatively simulate neurophysiological data about MSTd cell properties and psychophysical data about human navigation. Model cells match MSTd neuron responses to optic flow stimuli placed in different parts of the visual field, including position invariance, tuning curves, preferred spiral directions, direction reversals, average response curves and preferred locations for stimulus motion centers. The model shows how the preferred motion direction of the most active MSTd cells can explain human judgments of self-motion direction (heading), without using complex heading templates. The model explains when extraretinal eye movement signals are needed for accurate heading perception, and when retinal input is sufficient, and how heading judgments depend on scene layouts and rotation rates.

  20. Mapping human brain networks with cortico-cortical evoked potentials

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    Keller, Corey J.; Honey, Christopher J.; Mégevand, Pierre; Entz, Laszlo; Ulbert, Istvan; Mehta, Ashesh D.

    2014-01-01

    The cerebral cortex forms a sheet of neurons organized into a network of interconnected modules that is highly expanded in humans and presumably enables our most refined sensory and cognitive abilities. The links of this network form a fundamental aspect of its organization, and a great deal of research is focusing on understanding how information flows within and between different regions. However, an often-overlooked element of this connectivity regards a causal, hierarchical structure of regions, whereby certain nodes of the cortical network may exert greater influence over the others. While this is difficult to ascertain non-invasively, patients undergoing invasive electrode monitoring for epilepsy provide a unique window into this aspect of cortical organization. In this review, we highlight the potential for cortico-cortical evoked potential (CCEP) mapping to directly measure neuronal propagation across large-scale brain networks with spatio-temporal resolution that is superior to traditional neuroimaging methods. We first introduce effective connectivity and discuss the mechanisms underlying CCEP generation. Next, we highlight how CCEP mapping has begun to provide insight into the neural basis of non-invasive imaging signals. Finally, we present a novel approach to perturbing and measuring brain network function during cognitive processing. The direct measurement of CCEPs in response to electrical stimulation represents a potentially powerful clinical and basic science tool for probing the large-scale networks of the human cerebral cortex. PMID:25180306

  1. Effects of Aging on Cortical Neural Dynamics and Local Sleep Homeostasis in Mice.

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    McKillop, Laura E; Fisher, Simon P; Cui, Nanyi; Peirson, Stuart N; Foster, Russell G; Wafford, Keith A; Vyazovskiy, Vladyslav V

    2018-04-18

    Healthy aging is associated with marked effects on sleep, including its daily amount and architecture, as well as the specific EEG oscillations. Neither the neurophysiological underpinnings nor the biological significance of these changes are understood, and crucially the question remains whether aging is associated with reduced sleep need or a diminished capacity to generate sufficient sleep. Here we tested the hypothesis that aging may affect local cortical networks, disrupting the capacity to generate and sustain sleep oscillations, and with it the local homeostatic response to sleep loss. We performed chronic recordings of cortical neural activity and local field potentials from the motor cortex in young and older male C57BL/6J mice, during spontaneous waking and sleep, as well as during sleep after sleep deprivation. In older animals, we observed an increase in the incidence of non-rapid eye movement sleep local field potential slow waves and their associated neuronal silent (OFF) periods, whereas the overall pattern of state-dependent cortical neuronal firing was generally similar between ages. Furthermore, we observed that the response to sleep deprivation at the level of local cortical network activity was not affected by aging. Our data thus suggest that the local cortical neural dynamics and local sleep homeostatic mechanisms, at least in the motor cortex, are not impaired during healthy senescence in mice. This indicates that powerful protective or compensatory mechanisms may exist to maintain neuronal function stable across the life span, counteracting global changes in sleep amount and architecture. SIGNIFICANCE STATEMENT The biological significance of age-dependent changes in sleep is unknown but may reflect either a diminished sleep need or a reduced capacity to generate deep sleep stages. As aging has been linked to profound disruptions in cortical sleep oscillations and because sleep need is reflected in specific patterns of cortical activity, we

  2. Neural control of adrenal medullary and cortical blood flow during hemorrhage

    International Nuclear Information System (INIS)

    Breslow, M.J.; Jordan, D.A.; Thellman, S.T.; Traystman, R.J.

    1987-01-01

    Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, the authors compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Carbonized microspheres labeled with 153 Gd, 114 In, 113 Sn, 103 Ru, 95 Nb or 46 Se were used. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. They conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension

  3. A synergy-based hand control is encoded in human motor cortical areas

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    Leo, Andrea; Handjaras, Giacomo; Bianchi, Matteo; Marino, Hamal; Gabiccini, Marco; Guidi, Andrea; Scilingo, Enzo Pasquale; Pietrini, Pietro; Bicchi, Antonio; Santello, Marco; Ricciardi, Emiliano

    2016-01-01

    How the human brain controls hand movements to carry out different tasks is still debated. The concept of synergy has been proposed to indicate functional modules that may simplify the control of hand postures by simultaneously recruiting sets of muscles and joints. However, whether and to what extent synergic hand postures are encoded as such at a cortical level remains unknown. Here, we combined kinematic, electromyography, and brain activity measures obtained by functional magnetic resonance imaging while subjects performed a variety of movements towards virtual objects. Hand postural information, encoded through kinematic synergies, were represented in cortical areas devoted to hand motor control and successfully discriminated individual grasping movements, significantly outperforming alternative somatotopic or muscle-based models. Importantly, hand postural synergies were predicted by neural activation patterns within primary motor cortex. These findings support a novel cortical organization for hand movement control and open potential applications for brain-computer interfaces and neuroprostheses. DOI: http://dx.doi.org/10.7554/eLife.13420.001 PMID:26880543

  4. Characterization of Early Cortical Neural Network Development in Multiwell Microelectrode Array Plates

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    We examined the development of neural network activity using microelectrode array (MEA) recordings made in multi-well MEA plates (mwMEAs) over the first 12 days in vitro (DIV). In primary cortical cultures made from postnatal rats, action potential spiking activity was essentiall...

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

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    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.

  6. Quantitative Live Imaging of Human Embryonic Stem Cell Derived Neural Rosettes Reveals Structure-Function Dynamics Coupled to Cortical Development.

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    Ziv, Omer; Zaritsky, Assaf; Yaffe, Yakey; Mutukula, Naresh; Edri, Reuven; Elkabetz, Yechiel

    2015-10-01

    Neural stem cells (NSCs) are progenitor cells for brain development, where cellular spatial composition (cytoarchitecture) and dynamics are hypothesized to be linked to critical NSC capabilities. However, understanding cytoarchitectural dynamics of this process has been limited by the difficulty to quantitatively image brain development in vivo. Here, we study NSC dynamics within Neural Rosettes--highly organized multicellular structures derived from human pluripotent stem cells. Neural rosettes contain NSCs with strong epithelial polarity and are expected to perform apical-basal interkinetic nuclear migration (INM)--a hallmark of cortical radial glial cell development. We developed a quantitative live imaging framework to characterize INM dynamics within rosettes. We first show that the tendency of cells to follow the INM orientation--a phenomenon we referred to as radial organization, is associated with rosette size, presumably via mechanical constraints of the confining structure. Second, early forming rosettes, which are abundant with founder NSCs and correspond to the early proliferative developing cortex, show fast motions and enhanced radial organization. In contrast, later derived rosettes, which are characterized by reduced NSC capacity and elevated numbers of differentiated neurons, and thus correspond to neurogenesis mode in the developing cortex, exhibit slower motions and decreased radial organization. Third, later derived rosettes are characterized by temporal instability in INM measures, in agreement with progressive loss in rosette integrity at later developmental stages. Finally, molecular perturbations of INM by inhibition of actin or non-muscle myosin-II (NMII) reduced INM measures. Our framework enables quantification of cytoarchitecture NSC dynamics and may have implications in functional molecular studies, drug screening, and iPS cell-based platforms for disease modeling.

  7. Quantitative Live Imaging of Human Embryonic Stem Cell Derived Neural Rosettes Reveals Structure-Function Dynamics Coupled to Cortical Development.

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    Omer Ziv

    2015-10-01

    Full Text Available Neural stem cells (NSCs are progenitor cells for brain development, where cellular spatial composition (cytoarchitecture and dynamics are hypothesized to be linked to critical NSC capabilities. However, understanding cytoarchitectural dynamics of this process has been limited by the difficulty to quantitatively image brain development in vivo. Here, we study NSC dynamics within Neural Rosettes--highly organized multicellular structures derived from human pluripotent stem cells. Neural rosettes contain NSCs with strong epithelial polarity and are expected to perform apical-basal interkinetic nuclear migration (INM--a hallmark of cortical radial glial cell development. We developed a quantitative live imaging framework to characterize INM dynamics within rosettes. We first show that the tendency of cells to follow the INM orientation--a phenomenon we referred to as radial organization, is associated with rosette size, presumably via mechanical constraints of the confining structure. Second, early forming rosettes, which are abundant with founder NSCs and correspond to the early proliferative developing cortex, show fast motions and enhanced radial organization. In contrast, later derived rosettes, which are characterized by reduced NSC capacity and elevated numbers of differentiated neurons, and thus correspond to neurogenesis mode in the developing cortex, exhibit slower motions and decreased radial organization. Third, later derived rosettes are characterized by temporal instability in INM measures, in agreement with progressive loss in rosette integrity at later developmental stages. Finally, molecular perturbations of INM by inhibition of actin or non-muscle myosin-II (NMII reduced INM measures. Our framework enables quantification of cytoarchitecture NSC dynamics and may have implications in functional molecular studies, drug screening, and iPS cell-based platforms for disease modeling.

  8. Humans mimicking animals: A cortical hierarchy for human vocal communication sounds

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    Talkington, William J.; Rapuano, Kristina M.; Hitt, Laura; Frum, Chris A.; Lewis, James W.

    2012-01-01

    Numerous species possess cortical regions that are most sensitive to vocalizations produced by their own kind (conspecifics). In humans, the superior temporal sulci (STS) putatively represent homologous voice-sensitive areas of cortex. However, STS regions have recently been reported to represent auditory experience or “expertise” in general rather than showing exclusive sensitivity to human vocalizations per se. Using functional magnetic resonance imaging and a unique non-stereotypical category of complex human non-verbal vocalizations – human-mimicked versions of animal vocalizations – we found a cortical hierarchy in humans optimized for processing meaningful conspecific utterances. This left-lateralized hierarchy originated near primary auditory cortices and progressed into traditional speech-sensitive areas. These results suggest that the cortical regions supporting vocalization perception are initially organized by sensitivity to the human vocal tract in stages prior to the STS. Additionally, these findings have implications for the developmental time course of conspecific vocalization processing in humans as well as its evolutionary origins. PMID:22674283

  9. Neural synchrony in cortical networks: history, concept and current status

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    Peter Uhlhaas

    2009-07-01

    Full Text Available Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies.

  10. Human motor cortical activity recorded with Micro-ECoG electrodes, during individual finger movements.

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    Wang, W; Degenhart, A D; Collinger, J L; Vinjamuri, R; Sudre, G P; Adelson, P D; Holder, D L; Leuthardt, E C; Moran, D W; Boninger, M L; Schwartz, A B; Crammond, D J; Tyler-Kabara, E C; Weber, D J

    2009-01-01

    In this study human motor cortical activity was recorded with a customized micro-ECoG grid during individual finger movements. The quality of the recorded neural signals was characterized in the frequency domain from three different perspectives: (1) coherence between neural signals recorded from different electrodes, (2) modulation of neural signals by finger movement, and (3) accuracy of finger movement decoding. It was found that, for the high frequency band (60-120 Hz), coherence between neighboring micro-ECoG electrodes was 0.3. In addition, the high frequency band showed significant modulation by finger movement both temporally and spatially, and a classification accuracy of 73% (chance level: 20%) was achieved for individual finger movement using neural signals recorded from the micro-ECoG grid. These results suggest that the micro-ECoG grid presented here offers sufficient spatial and temporal resolution for the development of minimally-invasive brain-computer interface applications.

  11. Network bursts in cortical neuronal cultures: 'noise - versus pacemaker'- driven neural network simulations

    NARCIS (Netherlands)

    Gritsun, T.; Stegenga, J.; le Feber, Jakob; Rutten, Wim

    2009-01-01

    In this paper we address the issue of spontaneous bursting activity in cortical neuronal cultures and explain what might cause this collective behavior using computer simulations of two different neural network models. While the common approach to acivate a passive network is done by introducing

  12. Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

    Science.gov (United States)

    Uga, Minako; Saito, Toshiyuki; Sano, Toshifumi; Yokota, Hidenori; Oguro, Keiji; Rizki, Edmi Edison; Mizutani, Tsutomu; Katura, Takusige; Dan, Ippeita; Watanabe, Eiju

    2014-05-01

    Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains. Copyright © 2014. Published by Elsevier Inc.

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

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    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

  14. Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells.

    Science.gov (United States)

    Chandrasekaran, Abinaya; Avci, Hasan X; Ochalek, Anna; Rösingh, Lone N; Molnár, Kinga; László, Lajos; Bellák, Tamás; Téglási, Annamária; Pesti, Krisztina; Mike, Arpad; Phanthong, Phetcharat; Bíró, Orsolya; Hall, Vanessa; Kitiyanant, Narisorn; Krause, Karl-Heinz; Kobolák, Julianna; Dinnyés, András

    2017-12-01

    Neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) are frequently induced using 3D culture methodologies however, it is unknown whether spheroid-based (3D) neural induction is actually superior to monolayer (2D) neural induction. Our aim was to compare the efficiency of 2D induction with 3D induction method in their ability to generate NPCs, and subsequently neurons and astrocytes. Neural differentiation was analysed at the protein level qualitatively by immunocytochemistry and quantitatively by flow cytometry for NPC (SOX1, PAX6, NESTIN), neuronal (MAP2, TUBB3), cortical layer (TBR1, CUX1) and glial markers (SOX9, GFAP, AQP4). Electron microscopy demonstrated that both methods resulted in morphologically similar neural rosettes. However, quantification of NPCs derived from 3D neural induction exhibited an increase in the number of PAX6/NESTIN double positive cells and the derived neurons exhibited longer neurites. In contrast, 2D neural induction resulted in more SOX1 positive cells. While 2D monolayer induction resulted in slightly less mature neurons, at an early stage of differentiation, the patch clamp analysis failed to reveal any significant differences between the electrophysiological properties between the two induction methods. In conclusion, 3D neural induction increases the yield of PAX6 + /NESTIN + cells and gives rise to neurons with longer neurites, which might be an advantage for the production of forebrain cortical neurons, highlighting the potential of 3D neural induction, independent of iPSCs' genetic background. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Evidence for cortical structural plasticity in humans after a day of waking and sleep deprivation.

    Science.gov (United States)

    Elvsåshagen, Torbjørn; Zak, Nathalia; Norbom, Linn B; Pedersen, Per Ø; Quraishi, Sophia H; Bjørnerud, Atle; Alnæs, Dag; Doan, Nhat Trung; Malt, Ulrik F; Groote, Inge R; Westlye, Lars T

    2017-08-01

    Sleep is an evolutionarily conserved process required for human health and functioning. Insufficient sleep causes impairments across cognitive domains, and sleep deprivation can have rapid antidepressive effects in mood disorders. However, the neurobiological effects of waking and sleep are not well understood. Recently, animal studies indicated that waking and sleep are associated with substantial cortical structural plasticity. Here, we hypothesized that structural plasticity can be observed after a day of waking and sleep deprivation in the human cerebral cortex. To test this hypothesis, 61 healthy adult males underwent structural magnetic resonance imaging (MRI) at three time points: in the morning after a regular night's sleep, the evening of the same day, and the next morning, either after total sleep deprivation (N=41) or a night of sleep (N=20). We found significantly increased right prefrontal cortical thickness from morning to evening across all participants. In addition, pairwise comparisons in the deprived group between the two morning scans showed significant thinning of mainly bilateral medial parietal cortices after 23h of sleep deprivation, including the precuneus and posterior cingulate cortex. However, there were no significant group (sleep vs. sleep deprived group) by time interactions and we can therefore not rule out that other mechanisms than sleep deprivation per se underlie the bilateral medial parietal cortical thinning observed in the deprived group. Nonetheless, these cortices are thought to subserve wakefulness, are among the brain regions with highest metabolic rate during wake, and are considered some of the most sensitive cortical regions to a variety of insults. Furthermore, greater thinning within the left medial parietal cluster was associated with increased sleepiness after sleep deprivation. Together, these findings add to a growing body of data showing rapid structural plasticity within the human cerebral cortex detectable with

  16. Sall1 regulates cortical neurogenesis and laminar fate specification in mice: implications for neural abnormalities in Townes-Brocks syndrome

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    Susan J. Harrison

    2012-05-01

    Progenitor cells in the cerebral cortex undergo dynamic cellular and molecular changes during development. Sall1 is a putative transcription factor that is highly expressed in progenitor cells during development. In humans, the autosomal dominant developmental disorder Townes-Brocks syndrome (TBS is associated with mutations of the SALL1 gene. TBS is characterized by renal, anal, limb and auditory abnormalities. Although neural deficits have not been recognized as a diagnostic characteristic of the disease, ∼10% of patients exhibit neural or behavioral abnormalities. We demonstrate that, in addition to being expressed in peripheral organs, Sall1 is robustly expressed in progenitor cells of the central nervous system in mice. Both classical- and conditional-knockout mouse studies indicate that the cerebral cortex is particularly sensitive to loss of Sall1. In the absence of Sall1, both the surface area and depth of the cerebral cortex were decreased at embryonic day 18.5 (E18.5. These deficiencies are associated with changes in progenitor cell properties during development. In early cortical progenitor cells, Sall1 promotes proliferative over neurogenic division, whereas, at later developmental stages, Sall1 regulates the production and differentiation of intermediate progenitor cells. Furthermore, Sall1 influences the temporal specification of cortical laminae. These findings present novel insights into the function of Sall1 in the developing mouse cortex and provide avenues for future research into potential neural deficits in individuals with TBS.

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

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    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.

  18. Detection of an inhibitory cortical gradient underlying peak shift in learning: a neural basis for a false memory.

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    Miasnikov, Alexandre A; Weinberger, Norman M

    2012-11-01

    Experience often does not produce veridical memory. Understanding false attribution of events constitutes an important problem in memory research. "Peak shift" is a well-characterized, controllable phenomenon in which human and animal subjects that receive reinforcement associated with one sensory stimulus later respond maximally to another stimulus in post-training stimulus generalization tests. Peak shift ordinarily develops in discrimination learning (reinforced CS+, unreinforced CS-) and has long been attributed to the interaction of an excitatory gradient centered on the CS+ and an inhibitory gradient centered on the CS-; the shift is away from the CS-. In contrast, we have obtained peak shifts during single tone frequency training, using stimulation of the cholinergic nucleus basalis (NB) to implant behavioral memory into the rat. As we also recorded cortical activity, we took the opportunity to investigate the possible existence of a neural frequency gradient that could account for behavioral peak shift. Behavioral frequency generalization gradients (FGGs, interruption of ongoing respiration) were determined twice before training while evoked potentials were recorded from the primary auditory cortex (A1), to obtain a baseline gradient of "habituatory" neural decrement. A post-training behavioral FGG obtained 24h after three daily sessions of a single tone paired with NB stimulation (200 trials/day) revealed a peak shift. The peak of the FGG was at a frequency lower than the CS while the cortical inhibitory gradient was at a frequency higher than the CS frequency. Further analysis indicated that the frequency location and magnitude of the gradient could account for the behavioral peak shift. These results provide a neural basis for a systematic case of memory misattribution and may provide an animal model for the study of the neural bases of a type of "false memory". Published by Elsevier Inc.

  19. Dual roles for spike signaling in cortical neural populations

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    Dana eBallard

    2011-06-01

    Full Text Available A prominent feature of signaling in cortical neurons is that of randomness in the action potential. The output of a typical pyramidal cell can be well fit with a Poisson model, and variations in the Poisson rate repeatedly have been shown to be correlated with stimuli. However while the rate provides a very useful characterization of neural spike data, it may not be the most fundamental description of the signaling code. Recent data showing γ frequency range multi-cell action potential correlations, together with spike timing dependent plasticity, are spurring a re-examination of the classical model, since precise timing codes imply that the generation of spikes is essentially deterministic. Could the observed Poisson randomness and timing determinism reflect two separate modes of communication, or do they somehow derive from a single process? We investigate in a timing-based model whether the apparent incompatibility between these probabilistic and deterministic observations may be resolved by examining how spikes could be used in the underlying neural circuits. The crucial component of this model draws on dual roles for spike signaling. In learning receptive fields from ensembles of inputs, spikes need to behave probabilistically, whereas for fast signaling of individual stimuli, the spikes need to behave deterministically. Our simulations show that this combination is possible if deterministic signals using γ latency coding are probabilistically routed through different members of a cortical cell population at different times. This model exhibits standard features characteristic of Poisson models such as orientation tuning post-stimulus histograms and exponential interval histograms. In addition it makes testable predictions that follow from the γ latency coding.

  20. Vision first? The development of primary visual cortical networks is more rapid than the development of primary motor networks in humans.

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    Patricia Gervan

    Full Text Available The development of cortical functions and the capacity of the mature brain to learn are largely determined by the establishment and maintenance of neocortical networks. Here we address the human development of long-range connectivity in primary visual and motor cortices, using well-established behavioral measures--a Contour Integration test and a Finger-tapping task--that have been shown to be related to these specific primary areas, and the long-range neural connectivity within those. Possible confounding factors, such as different task requirements (complexity, cognitive load are eliminated by using these tasks in a learning paradigm. We find that there is a temporal lag between the developmental timing of primary sensory vs. motor areas with an advantage of visual development; we also confirm that human development is very slow in both cases, and that there is a retained capacity for practice induced plastic changes in adults. This pattern of results seems to point to human-specific development of the "canonical circuits" of primary sensory and motor cortices, probably reflecting the ecological requirements of human life.

  1. Cortical representations of communication sounds.

    Science.gov (United States)

    Heiser, Marc A; Cheung, Steven W

    2008-10-01

    This review summarizes recent research into cortical processing of vocalizations in animals and humans. There has been a resurgent interest in this topic accompanied by an increased number of studies using animal models with complex vocalizations and new methods in human brain imaging. Recent results from such studies are discussed. Experiments have begun to reveal the bilateral cortical fields involved in communication sound processing and the transformations of neural representations that occur among those fields. Advances have also been made in understanding the neuronal basis of interaction between developmental exposures and behavioral experiences with vocalization perception. Exposure to sounds during the developmental period produces large effects on brain responses, as do a variety of specific trained tasks in adults. Studies have also uncovered a neural link between the motor production of vocalizations and the representation of vocalizations in cortex. Parallel experiments in humans and animals are answering important questions about vocalization processing in the central nervous system. This dual approach promises to reveal microscopic, mesoscopic, and macroscopic principles of large-scale dynamic interactions between brain regions that underlie the complex phenomenon of vocalization perception. Such advances will yield a greater understanding of the causes, consequences, and treatment of disorders related to speech processing.

  2. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

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    Patrick eHecht

    2015-10-01

    Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

  3. Towards a theory of cortical columns: From spiking neurons to interacting neural populations of finite size.

    Science.gov (United States)

    Schwalger, Tilo; Deger, Moritz; Gerstner, Wulfram

    2017-04-01

    Neural population equations such as neural mass or field models are widely used to study brain activity on a large scale. However, the relation of these models to the properties of single neurons is unclear. Here we derive an equation for several interacting populations at the mesoscopic scale starting from a microscopic model of randomly connected generalized integrate-and-fire neuron models. Each population consists of 50-2000 neurons of the same type but different populations account for different neuron types. The stochastic population equations that we find reveal how spike-history effects in single-neuron dynamics such as refractoriness and adaptation interact with finite-size fluctuations on the population level. Efficient integration of the stochastic mesoscopic equations reproduces the statistical behavior of the population activities obtained from microscopic simulations of a full spiking neural network model. The theory describes nonlinear emergent dynamics such as finite-size-induced stochastic transitions in multistable networks and synchronization in balanced networks of excitatory and inhibitory neurons. The mesoscopic equations are employed to rapidly integrate a model of a cortical microcircuit consisting of eight neuron types, which allows us to predict spontaneous population activities as well as evoked responses to thalamic input. Our theory establishes a general framework for modeling finite-size neural population dynamics based on single cell and synapse parameters and offers an efficient approach to analyzing cortical circuits and computations.

  4. Highly efficient methods to obtain homogeneous dorsal neural progenitor cells from human and mouse embryonic stem cells and induced pluripotent stem cells.

    Science.gov (United States)

    Zhang, Meixiang; Ngo, Justine; Pirozzi, Filomena; Sun, Ying-Pu; Wynshaw-Boris, Anthony

    2018-03-15

    Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages. Here, we present three protocols that are highly efficient in differentiating mouse and human ESCs, as well as human iPSCs, into a homogeneous and stable population of dorsal NPCs. These protocols will be useful for modeling cerebral cortical neurological and neurodegenerative disorders in both mouse and human as well as for high-throughput drug screening for therapeutic development. We optimized three different strategies for generating dorsal telencephalic NPCs from mouse and human pluripotent cell types through single or double inhibition of bone morphogenetic protein (BMP) and/or SMAD pathways. Mouse and human pluripotent cells were aggregated to form embryoid bodies in suspension and were treated with dorsomorphin alone (BMP inhibition) or combined with SB431542 (double BMP/SMAD inhibition) during neural induction. Neural rosettes were then selected from plated embryoid bodies to purify the population of dorsal NPCs. We tested the expression of key dorsal NPC markers as well as nonectodermal markers to confirm the efficiency of our three methods in comparison to published and commercial protocols. Single and double inhibition of BMP and/or SMAD during neural induction led to the efficient differentiation of dorsal NPCs, based on the high percentage of PAX6-positive cells and the NPC gene expression profile. There were no statistically

  5. DYRK1A-mediated Cyclin D1 Degradation in Neural Stem Cells Contributes to the Neurogenic Cortical Defects in Down Syndrome

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    Sònia Najas

    2015-02-01

    Full Text Available Alterations in cerebral cortex connectivity lead to intellectual disability and in Down syndrome, this is associated with a deficit in cortical neurons that arises during prenatal development. However, the pathogenic mechanisms that cause this deficit have not yet been defined. Here we show that the human DYRK1A kinase on chromosome 21 tightly regulates the nuclear levels of Cyclin D1 in embryonic cortical stem (radial glia cells, and that a modest increase in DYRK1A protein in transgenic embryos lengthens the G1 phase in these progenitors. These alterations promote asymmetric proliferative divisions at the expense of neurogenic divisions, producing a deficit in cortical projection neurons that persists in postnatal stages. Moreover, radial glial progenitors in the Ts65Dn mouse model of Down syndrome have less Cyclin D1, and Dyrk1a is the triplicated gene that causes both early cortical neurogenic defects and decreased nuclear Cyclin D1 levels in this model. These data provide insights into the mechanisms that couple cell cycle regulation and neuron production in cortical neural stem cells, emphasizing that the deleterious effect of DYRK1A triplication in the formation of the cerebral cortex begins at the onset of neurogenesis, which is relevant to the search for early therapeutic interventions in Down syndrome.

  6. Human cortical responses to slow and fast binaural beats reveal multiple mechanisms of binaural hearing.

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    Ross, Bernhard; Miyazaki, Takahiro; Thompson, Jessica; Jamali, Shahab; Fujioka, Takako

    2014-10-15

    When two tones with slightly different frequencies are presented to both ears, they interact in the central auditory system and induce the sensation of a beating sound. At low difference frequencies, we perceive a single sound, which is moving across the head between the left and right ears. The percept changes to loudness fluctuation, roughness, and pitch with increasing beat rate. To examine the neural representations underlying these different perceptions, we recorded neuromagnetic cortical responses while participants listened to binaural beats at a continuously varying rate between 3 Hz and 60 Hz. Binaural beat responses were analyzed as neuromagnetic oscillations following the trajectory of the stimulus rate. Responses were largest in the 40-Hz gamma range and at low frequencies. Binaural beat responses at 3 Hz showed opposite polarity in the left and right auditory cortices. We suggest that this difference in polarity reflects the opponent neural population code for representing sound location. Binaural beats at any rate induced gamma oscillations. However, the responses were largest at 40-Hz stimulation. We propose that the neuromagnetic gamma oscillations reflect postsynaptic modulation that allows for precise timing of cortical neural firing. Systematic phase differences between bilateral responses suggest that separate sound representations of a sound object exist in the left and right auditory cortices. We conclude that binaural processing at the cortical level occurs with the same temporal acuity as monaural processing whereas the identification of sound location requires further interpretation and is limited by the rate of object representations. Copyright © 2014 the American Physiological Society.

  7. Real-time classification of auditory sentences using evoked cortical activity in humans

    Science.gov (United States)

    Moses, David A.; Leonard, Matthew K.; Chang, Edward F.

    2018-06-01

    Objective. Recent research has characterized the anatomical and functional basis of speech perception in the human auditory cortex. These advances have made it possible to decode speech information from activity in brain regions like the superior temporal gyrus, but no published work has demonstrated this ability in real-time, which is necessary for neuroprosthetic brain-computer interfaces. Approach. Here, we introduce a real-time neural speech recognition (rtNSR) software package, which was used to classify spoken input from high-resolution electrocorticography signals in real-time. We tested the system with two human subjects implanted with electrode arrays over the lateral brain surface. Subjects listened to multiple repetitions of ten sentences, and rtNSR classified what was heard in real-time from neural activity patterns using direct sentence-level and HMM-based phoneme-level classification schemes. Main results. We observed single-trial sentence classification accuracies of 90% or higher for each subject with less than 7 minutes of training data, demonstrating the ability of rtNSR to use cortical recordings to perform accurate real-time speech decoding in a limited vocabulary setting. Significance. Further development and testing of the package with different speech paradigms could influence the design of future speech neuroprosthetic applications.

  8. Electronic bypass of spinal lesions: activation of lower motor neurons directly driven by cortical neural signals.

    Science.gov (United States)

    Li, Yan; Alam, Monzurul; Guo, Shanshan; Ting, K H; He, Jufang

    2014-07-03

    Lower motor neurons in the spinal cord lose supraspinal inputs after complete spinal cord injury, leading to a loss of volitional control below the injury site. Extensive locomotor training with spinal cord stimulation can restore locomotion function after spinal cord injury in humans and animals. However, this locomotion is non-voluntary, meaning that subjects cannot control stimulation via their natural "intent". A recent study demonstrated an advanced system that triggers a stimulator using forelimb stepping electromyographic patterns to restore quadrupedal walking in rats with spinal cord transection. However, this indirect source of "intent" may mean that other non-stepping forelimb activities may false-trigger the spinal stimulator and thus produce unwanted hindlimb movements. We hypothesized that there are distinguishable neural activities in the primary motor cortex during treadmill walking, even after low-thoracic spinal transection in adult guinea pigs. We developed an electronic spinal bridge, called "Motolink", which detects these neural patterns and triggers a "spinal" stimulator for hindlimb movement. This hardware can be head-mounted or carried in a backpack. Neural data were processed in real-time and transmitted to a computer for analysis by an embedded processor. Off-line neural spike analysis was conducted to calculate and preset the spike threshold for "Motolink" hardware. We identified correlated activities of primary motor cortex neurons during treadmill walking of guinea pigs with spinal cord transection. These neural activities were used to predict the kinematic states of the animals. The appropriate selection of spike threshold value enabled the "Motolink" system to detect the neural "intent" of walking, which triggered electrical stimulation of the spinal cord and induced stepping-like hindlimb movements. We present a direct cortical "intent"-driven electronic spinal bridge to restore hindlimb locomotion after complete spinal cord injury.

  9. Convergent dysregulation of frontal cortical cognitive and reward systems in eating disorders.

    Science.gov (United States)

    Stefano, George B; Ptáček, Radek; Kuželová, Hana; Mantione, Kirk J; Raboch, Jiří; Papezova, Hana; Kream, Richard M

    2013-05-10

    A substantive literature has drawn a compelling case for the functional involvement of mesolimbic/prefrontal cortical neural reward systems in normative control of eating and in the etiology and persistence of severe eating disorders that affect diverse human populations. Presently, we provide a short review that develops an equally compelling case for the importance of dysregulated frontal cortical cognitive neural networks acting in concert with regional reward systems in the regulation of complex eating behaviors and in the presentation of complex pathophysiological symptoms associated with major eating disorders. Our goal is to highlight working models of major eating disorders that incorporate complementary approaches to elucidate functionally interactive neural circuits defined by their regulatory neurochemical phenotypes. Importantly, we also review evidence-based linkages between widely studied psychiatric and neurodegenerative syndromes (e.g., autism spectrum disorders and Parkinson's disease) and co-morbid eating disorders to elucidate basic mechanisms involving dopaminergic transmission and its regulation by endogenously expressed morphine in these same cortical regions.

  10. 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

  11. Towards a theory of cortical columns: From spiking neurons to interacting neural populations of finite size

    Science.gov (United States)

    Gerstner, Wulfram

    2017-01-01

    Neural population equations such as neural mass or field models are widely used to study brain activity on a large scale. However, the relation of these models to the properties of single neurons is unclear. Here we derive an equation for several interacting populations at the mesoscopic scale starting from a microscopic model of randomly connected generalized integrate-and-fire neuron models. Each population consists of 50–2000 neurons of the same type but different populations account for different neuron types. The stochastic population equations that we find reveal how spike-history effects in single-neuron dynamics such as refractoriness and adaptation interact with finite-size fluctuations on the population level. Efficient integration of the stochastic mesoscopic equations reproduces the statistical behavior of the population activities obtained from microscopic simulations of a full spiking neural network model. The theory describes nonlinear emergent dynamics such as finite-size-induced stochastic transitions in multistable networks and synchronization in balanced networks of excitatory and inhibitory neurons. The mesoscopic equations are employed to rapidly integrate a model of a cortical microcircuit consisting of eight neuron types, which allows us to predict spontaneous population activities as well as evoked responses to thalamic input. Our theory establishes a general framework for modeling finite-size neural population dynamics based on single cell and synapse parameters and offers an efficient approach to analyzing cortical circuits and computations. PMID:28422957

  12. Comparative cortical bone thickness between the long bones of humans and five common non-human mammal taxa.

    Science.gov (United States)

    Croker, Sarah L; Reed, Warren; Donlon, Denise

    2016-03-01

    The task of identifying fragments of long bone shafts as human or non-human is difficult but necessary, for both forensic and archaeological cases, and a fast simple method is particularly useful. Previous literature suggests there may be differences in the thickness of the cortical bone between these two groups, but this has not been tested thoroughly. The aim of this study was not only to test this suggestion, but also to provide data that could be of practical assistance for future comparisons. The major limb bones (humerus, radius, femur and tibia) of 50 Caucasoid adult skeletons of known age and sex were radiographed, along with corresponding skeletal elements from sheep, pigs, cattle, large dogs and kangaroos. Measurements were taken from the radiographs at five points along the bone shaft, of shaft diameter, cortical bone thickness, and a cortical thickness index (sum of cortices divided by shaft diameter) in both anteroposterior and mediolateral orientations. Each variable for actual cortical bone thickness as well as cortical thickness indices were compared between the human group (split by sex) and each of the non-human groups in turn, using Student's t-tests. Results showed that while significant differences did exist between the human groups and many of the non-human groups, these were not all in the same direction. That is, some variables in the human groups were significantly greater than, and others were significantly less than, the corresponding variable in the non-human groups, depending on the particular non-human group, sex of the human group, or variable under comparison. This was the case for measurements of both actual cortical bone thickness and cortical thickness index. Therefore, for bone shaft fragments for which the skeletal element is unknown, the overlap in cortical bone thickness between different areas of different bones is too great to allow identification using this method alone. However, by providing extensive cortical bone

  13. Human occipital cortices differentially exert saccadic suppression: intracranial recording in children

    Science.gov (United States)

    Uematsu, Mitsugu; Matsuzaki, Naoyuki; Brown, Erik C.; Kojima, Katsuaki; Asano, Eishi

    2013-01-01

    By repeating saccades unconsciously, humans explore the surrounding world every day. Saccades inevitably move external visual images across the retina at high velocity; nonetheless, healthy humans don’t perceive transient blurring of the visual scene during saccades. This perceptual stability is referred to as saccadic suppression. Functional suppression is believed to take place transiently in the visual systems, but it remains unknown how commonly or differentially the human occipital lobe activities are suppressed at the large-scale cortical network level. We determined the spatial-temporal dynamics of intracranially-recorded gamma activity at 80–150 Hz around spontaneous saccades under no-task conditions during wakefulness and those in darkness during REM sleep. Regardless of wakefulness or REM sleep, a small degree of attenuation of gamma activity was noted in the occipital regions during saccades, most extensively in the polar and least in the medial portions. Longer saccades were associated with more intense gamma-attenuation. Gamma-attenuation was subsequently followed by gamma-augmentation most extensively involving the medial and least involving the polar occipital region. Such gamma-augmentation was more intense during wakefulness and temporally locked to the offset of saccades. The polarities of initial peaks of perisaccadic event-related potentials (ERPs) were frequently positive in the medial and negative in the polar occipital regions. The present study, for the first time, provided the electrophysiological evidence that human occipital cortices differentially exert peri-saccadic modulation. Transiently suppressed sensitivity of the primary visual cortex in the polar region may be an important neural basis for saccadic suppression. Presence of occipital gamma-attenuation even during REM sleep suggests that saccadic suppression might be exerted even without external visual inputs. The primary visual cortex in the medial region, compared to the

  14. Lifespan anxiety is reflected in human amygdala cortical connectivity

    Science.gov (United States)

    He, Ye; Xu, Ting; Zhang, Wei

    2016-01-01

    Abstract The amygdala plays a pivotal role in processing anxiety and connects to large‐scale brain networks. However, intrinsic functional connectivity (iFC) between amygdala and these networks has rarely been examined in relation to anxiety, especially across the lifespan. We employed resting‐state functional MRI data from 280 healthy adults (18–83.5 yrs) to elucidate the relationship between anxiety and amygdala iFC with common cortical networks including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default network. Global and network‐specific iFC were separately computed as mean iFC of amygdala with the entire cerebral cortex and each cortical network. We detected negative correlation between global positive amygdala iFC and trait anxiety. Network‐specific associations between amygdala iFC and anxiety were also detectable. Specifically, the higher iFC strength between the left amygdala and the limbic network predicted lower state anxiety. For the trait anxiety, left amygdala anxiety–connectivity correlation was observed in both somatomotor and dorsal attention networks, whereas the right amygdala anxiety–connectivity correlation was primarily distributed in the frontoparietal and ventral attention networks. Ventral attention network exhibited significant anxiety–gender interactions on its iFC with amygdala. Together with findings from additional vertex‐wise analysis, these data clearly indicated that both low‐level sensory networks and high‐level associative networks could contribute to detectable predictions of anxiety behaviors by their iFC profiles with the amygdala. This set of systems neuroscience findings could lead to novel functional network models on neural correlates of human anxiety and provide targets for novel treatment strategies on anxiety disorders. Hum Brain Mapp 37:1178–1193, 2016. © 2015 The Authors Human Brain Mapping

  15. Visualization of migration of human cortical neurons generated from induced pluripotent stem cells.

    Science.gov (United States)

    Bamba, Yohei; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

    2017-09-01

    Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly. Our system needs no viable brain tissue, which is usually used in slice culture. Migratory behavior of human cortical neuron can be observed more easily and more vividly by its fluorescence and glial scaffold than that by earlier methods. Our in vitro experimental system provides a new platform for investigating development of the human central nervous system and brain malformation. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Developmental changes in human dopamine neurotransmission: cortical receptors and terminators

    Directory of Open Access Journals (Sweden)

    Rothmond Debora A

    2012-02-01

    Full Text Available Abstract Background Dopamine is integral to cognition, learning and memory, and dysfunctions of the frontal cortical dopamine system have been implicated in several developmental neuropsychiatric disorders. The dorsolateral prefrontal cortex (DLPFC is critical for working memory which does not fully mature until the third decade of life. Few studies have reported on the normal development of the dopamine system in human DLPFC during postnatal life. We assessed pre- and postsynaptic components of the dopamine system including tyrosine hydroxylase, the dopamine receptors (D1, D2 short and D2 long isoforms, D4, D5, catechol-O-methyltransferase, and monoamine oxidase (A and B in the developing human DLPFC (6 weeks -50 years. Results Gene expression was first analysed by microarray and then by quantitative real-time PCR. Protein expression was analysed by western blot. Protein levels for tyrosine hydroxylase peaked during the first year of life (p O-methyltransferase (p = 0.024 were significantly higher in neonates and infants as was catechol-O-methyltransferase protein (32 kDa, p = 0.027. In contrast, dopamine D1 receptor mRNA correlated positively with age (p = 0.002 and dopamine D1 receptor protein expression increased throughout development (p Conclusions We find distinct developmental changes in key components of the dopamine system in DLPFC over postnatal life. Those genes that are highly expressed during the first year of postnatal life may influence and orchestrate the early development of cortical neural circuitry while genes portraying a pattern of increasing expression with age may indicate a role in DLPFC maturation and attainment of adult levels of cognitive function.

  17. Assessment of cortical dysfunction in human strabismic amblyopia using magnetoencephalography (MEG)

    International Nuclear Information System (INIS)

    Anderson, S.J.; Holliday, I.E.; Harding, G.F.A.

    1999-01-01

    The aim of this study was to use the technique of magnetoencephalography (MEG) to determine the effects of strabismic amblyopia on the processing of spatial information within the occipital cortex of humans. We recorded evoked magnetic responses to the onset of a chromatic (red/green) sinusoidal grating of periodicity 0.5-4.0 c deg -1 using a 19-channel SQUID-based neuromagnetometer. Evoked responses were recorded monocularly on six amblyopes and six normally-sighted controls, the stimuli being positioned near the fovea in the lower right visual field of each observer. For comparison, the spatial contrast sensitivity function (CSF) for the detection of chromatic gratings was measured for one amblyope and one control using a two alternate forced-choice psychophysical procedure. We chose red/green sinusoids as our stimuli because they evoke strong magnetic responses from the occipital cortex in adult humans (Fylan, Holliday, Singh, Anderson and Harding. (1997). Neuroimage, 6, 47-57). Magnetic field strength was plotted as a function of stimulus spatial frequency for each eye of each subject. Interocular differences were only evident within the amblyopic group: for stimuli of 1-2 c deg -1 , the evoked responses had significantly longer latencies and reduced amplitudes through the amblyopic eye (P<0.05). Importantly, the extent of the deficit was uncorrelated with either Snellen acuity or contrast sensitivity. Localization of the evoked responses was performed using a single equivalent current dipole model. Source localizations, for both normal and amblyopic subjects, were consistent with neural activity at the occipital pole near the V1/V2 border. We conclude that MEG is sensitive to the deficit in cortical processing associated with human amblyopia, and can be used to make quantitative neurophysiological measurements. The nature of the cortical deficit is discussed. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  18. Early development of synchrony in cortical activations in the human.

    Science.gov (United States)

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Neural Determinants of Task Performance during Feature-Based Attention in Human Cortex

    Science.gov (United States)

    Gong, Mengyuan

    2018-01-01

    Abstract Studies of feature-based attention have associated activity in a dorsal frontoparietal network with putative attentional priority signals. Yet, how this neural activity mediates attentional selection and whether it guides behavior are fundamental questions that require investigation. We reasoned that endogenous fluctuations in the quality of attentional priority should influence task performance. Human subjects detected a speed increment while viewing clockwise (CW) or counterclockwise (CCW) motion (baseline task) or while attending to either direction amid distracters (attention task). In an fMRI experiment, direction-specific neural pattern similarity between the baseline task and the attention task revealed a higher level of similarity for correct than incorrect trials in frontoparietal regions. Using transcranial magnetic stimulation (TMS), we disrupted posterior parietal cortex (PPC) and found a selective deficit in the attention task, but not in the baseline task, demonstrating the necessity of this cortical area during feature-based attention. These results reveal that frontoparietal areas maintain attentional priority that facilitates successful behavioral selection. PMID:29497703

  20. Why we can talk, debate, and change our minds: neural circuits, basal ganglia operations, and transcriptional factors.

    Science.gov (United States)

    Lieberman, Philip

    2014-12-01

    Ackermann et al. disregard attested knowledge concerning aphasia, Parkinson disease, cortical-to-striatal circuits, basal ganglia, laryngeal phonation, and other matters. Their dual-pathway model cannot account for "what is special about the human brain." Their human cortical-to-laryngeal neural circuit does not exist. Basal ganglia operations, enhanced by mutations on FOXP2, confer human motor-control, linguistic, and cognitive capabilities.

  1. Histomorphometry and cortical robusticity of the adult human femur.

    Science.gov (United States)

    Miszkiewicz, Justyna Jolanta; Mahoney, Patrick

    2018-01-13

    Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n = 233) and female (n = 217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

  2. Characterization of Early Cortical Neural Network ...

    Science.gov (United States)

    We examined the development of neural network activity using microelectrode array (MEA) recordings made in multi-well MEA plates (mwMEAs) over the first 12 days in vitro (DIV). In primary cortical cultures made from postnatal rats, action potential spiking activity was essentially absent on DIV 2 and developed rapidly between DIV 5 and 12. Spiking activity was primarily sporadic and unorganized at early DIV, and became progressively more organized with time in culture, with bursting parameters, synchrony and network bursting increasing between DIV 5 and 12. We selected 12 features to describe network activity and principal components analysis using these features demonstrated a general segregation of data by age at both the well and plate levels. Using a combination of random forest classifiers and Support Vector Machines, we demonstrated that 4 features (CV of within burst ISI, CV of IBI, network spike rate and burst rate) were sufficient to predict the age (either DIV 5, 7, 9 or 12) of each well recording with >65% accuracy. When restricting the classification problem to a binary decision, we found that classification improved dramatically, e.g. 95% accuracy for discriminating DIV 5 vs DIV 12 wells. Further, we present a novel resampling approach to determine the number of wells that might be needed for conducting comparisons of different treatments using mwMEA plates. Overall, these results demonstrate that network development on mwMEA plates is similar to

  3. Cortical surface area and cortical thickness in the precuneus of adult humans.

    Science.gov (United States)

    Bruner, E; Román, F J; de la Cuétara, J M; Martin-Loeches, M; Colom, R

    2015-02-12

    The precuneus has received considerable attention in the last decade, because of its cognitive functions, its role as a central node of the brain networks, and its involvement in neurodegenerative processes. Paleoneurological studies suggested that form changes in the deep parietal areas represent a major character associated with the origin of the modern human brain morphology. A recent neuroanatomical survey based on shape analysis suggests that the proportions of the precuneus are also a determinant source of overall brain geometrical differences among adult individuals, influencing the brain spatial organization. Here, we evaluate the variation of cortical thickness and cortical surface area of the precuneus in a sample of adult humans, and their relation with geometry and cognition. Precuneal thickness and surface area are not correlated. There is a marked individual variation. The right precuneus is thinner and larger than the left one, but there are relevant fluctuating asymmetries, with only a modest correlation between the hemispheres. Males have a thicker cortex but differences in cortical area are not significant between sexes. The surface area of the precuneus shows a positive allometry with the brain surface area, although the correlation is modest. The dilation/contraction of the precuneus, described as a major factor of variability within adult humans, is associated with absolute increase/decrease of its surface, but not with variation in thickness. Precuneal thickness, precuneal surface area and precuneal morphology are not correlated with psychological factors such as intelligence, working memory, attention control, and processing speed, stressing further possible roles of this area in supporting default mode functions. Beyond gross morphology, the processes underlying the large phenotypic variation of the precuneus must be further investigated through specific cellular analyses, aimed at considering differences in cellular size, density

  4. Cortical depth dependent population receptive field attraction by spatial attention in human V1.

    Science.gov (United States)

    Klein, Barrie P; Fracasso, Alessio; van Dijk, Jelle A; Paffen, Chris L E; Te Pas, Susan F; Dumoulin, Serge O

    2018-04-27

    Visual spatial attention concentrates neural resources at the attended location. Recently, we demonstrated that voluntary spatial attention attracts population receptive fields (pRFs) toward its location throughout the visual hierarchy. Theoretically, both a feed forward or feedback mechanism could underlie pRF attraction in a given cortical area. Here, we use sub-millimeter ultra-high field functional MRI to measure pRF attraction across cortical depth and assess the contribution of feed forward and feedback signals to pRF attraction. In line with previous findings, we find consistent attraction of pRFs with voluntary spatial attention in V1. When assessed as a function of cortical depth, we find pRF attraction in every cortical portion (deep, center and superficial), although the attraction is strongest in deep cortical portions (near the gray-white matter boundary). Following the organization of feed forward and feedback processing across V1, we speculate that a mixture of feed forward and feedback processing underlies pRF attraction in V1. Specifically, we propose that feedback processing contributes to the pRF attraction in deep cortical portions. Copyright © 2018. Published by Elsevier Inc.

  5. An implantable wireless neural interface for recording cortical circuit dynamics in moving primates

    Science.gov (United States)

    Borton, David A.; Yin, Ming; Aceros, Juan; Nurmikko, Arto

    2013-04-01

    Objective. Neural interface technology suitable for clinical translation has the potential to significantly impact the lives of amputees, spinal cord injury victims and those living with severe neuromotor disease. Such systems must be chronically safe, durable and effective. Approach. We have designed and implemented a neural interface microsystem, housed in a compact, subcutaneous and hermetically sealed titanium enclosure. The implanted device interfaces the brain with a 510k-approved, 100-element silicon-based microelectrode array via a custom hermetic feedthrough design. Full spectrum neural signals were amplified (0.1 Hz to 7.8 kHz, 200× gain) and multiplexed by a custom application specific integrated circuit, digitized and then packaged for transmission. The neural data (24 Mbps) were transmitted by a wireless data link carried on a frequency-shift-key-modulated signal at 3.2 and 3.8 GHz to a receiver 1 m away by design as a point-to-point communication link for human clinical use. The system was powered by an embedded medical grade rechargeable Li-ion battery for 7 h continuous operation between recharge via an inductive transcutaneous wireless power link at 2 MHz. Main results. Device verification and early validation were performed in both swine and non-human primate freely-moving animal models and showed that the wireless implant was electrically stable, effective in capturing and delivering broadband neural data, and safe for over one year of testing. In addition, we have used the multichannel data from these mobile animal models to demonstrate the ability to decode neural population dynamics associated with motor activity. Significance. We have developed an implanted wireless broadband neural recording device evaluated in non-human primate and swine. The use of this new implantable neural interface technology can provide insight into how to advance human neuroprostheses beyond the present early clinical trials. Further, such tools enable mobile

  6. Syllabic discrimination in premature human infants prior to complete formation of cortical layers

    OpenAIRE

    Mahmoudzadeh, Mahdi; Dehaene-Lambertz, Ghislaine; Fournier, Marc; Kongolo, Guy; Goudjil, Sabrina; Dubois, Jessica; Grebe, Reinhard; Wallois, Fabrice

    2013-01-01

    The ontogeny of linguistic functions in the human brain remains elusive. Although some auditory capacities are described before term, whether and how such immature cortical circuits might process speech are unknown. Here we used functional optical imaging to evaluate the cerebral responses to syllables at the earliest age at which cortical responses to external stimuli can be recorded in humans (28- to 32-wk gestational age). At this age, the cortical organization in layers is not completed. ...

  7. Visual Working Memory Is Independent of the Cortical Spacing Between Memoranda.

    Science.gov (United States)

    Harrison, William J; Bays, Paul M

    2018-03-21

    The sensory recruitment hypothesis states that visual short-term memory is maintained in the same visual cortical areas that initially encode a stimulus' features. Although it is well established that the distance between features in visual cortex determines their visibility, a limitation known as crowding, it is unknown whether short-term memory is similarly constrained by the cortical spacing of memory items. Here, we investigated whether the cortical spacing between sequentially presented memoranda affects the fidelity of memory in humans (of both sexes). In a first experiment, we varied cortical spacing by taking advantage of the log-scaling of visual cortex with eccentricity, presenting memoranda in peripheral vision sequentially along either the radial or tangential visual axis with respect to the fovea. In a second experiment, we presented memoranda sequentially either within or beyond the critical spacing of visual crowding, a distance within which visual features cannot be perceptually distinguished due to their nearby cortical representations. In both experiments and across multiple measures, we found strong evidence that the ability to maintain visual features in memory is unaffected by cortical spacing. These results indicate that the neural architecture underpinning working memory has properties inconsistent with the known behavior of sensory neurons in visual cortex. Instead, the dissociation between perceptual and memory representations supports a role of higher cortical areas such as posterior parietal or prefrontal regions or may involve an as yet unspecified mechanism in visual cortex in which stimulus features are bound to their temporal order. SIGNIFICANCE STATEMENT Although much is known about the resolution with which we can remember visual objects, the cortical representation of items held in short-term memory remains contentious. A popular hypothesis suggests that memory of visual features is maintained via the recruitment of the same neural

  8. 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.

  9. Human temporal cortical single neuron activity during working memory maintenance.

    Science.gov (United States)

    Zamora, Leona; Corina, David; Ojemann, George

    2016-06-01

    The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

  10. Human Temporal Cortical Single Neuron Activity During Working Memory Maintenance

    Science.gov (United States)

    Zamora, Leona; Corina, David; Ojemann, George

    2016-01-01

    The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

  11. High-frequency oscillations in distributed neural networks reveal the dynamics of human decision making

    Directory of Open Access Journals (Sweden)

    Adrian G Guggisberg

    2008-03-01

    Full Text Available We examine the relative timing of numerous brain regions involved in human decisions that are based on external criteria, learned information, personal preferences, or unconstrained internal considerations. Using magnetoencephalography (MEG and advanced signal analysis techniques, we were able to non-invasively reconstruct oscillations of distributed neural networks in the high-gamma frequency band (60–150 Hz. The time course of the observed neural activity suggested that two-alternative forced choice tasks are processed in four overlapping stages: processing of sensory input, option evaluation, intention formation, and action execution. Visual areas are activated fi rst, and show recurring activations throughout the entire decision process. The temporo-occipital junction and the intraparietal sulcus are active during evaluation of external values of the options, 250–500 ms after stimulus presentation. Simultaneously, personal preference is mediated by cortical midline structures. Subsequently, the posterior parietal and superior occipital cortices appear to encode intention, with different subregions being responsible for different types of choice. The cerebellum and inferior parietal cortex are recruited for internal generation of decisions and actions, when all options have the same value. Action execution was accompanied by activation peaks in the contralateral motor cortex. These results suggest that high-gamma oscillations as recorded by MEG allow a reliable reconstruction of decision processes with excellent spatiotemporal resolution.

  12. Human Auditory and Adjacent Nonauditory Cerebral Cortices Are Hypermetabolic in Tinnitus as Measured by Functional Near-Infrared Spectroscopy (fNIRS).

    Science.gov (United States)

    Issa, Mohamad; Bisconti, Silvia; Kovelman, Ioulia; Kileny, Paul; Basura, Gregory J

    2016-01-01

    Tinnitus is the phantom perception of sound in the absence of an acoustic stimulus. To date, the purported neural correlates of tinnitus from animal models have not been adequately characterized with translational technology in the human brain. The aim of the present study was to measure changes in oxy-hemoglobin concentration from regions of interest (ROI; auditory cortex) and non-ROI (adjacent nonauditory cortices) during auditory stimulation and silence in participants with subjective tinnitus appreciated equally in both ears and in nontinnitus controls using functional near-infrared spectroscopy (fNIRS). Control and tinnitus participants with normal/near-normal hearing were tested during a passive auditory task. Hemodynamic activity was monitored over ROI and non-ROI under episodic periods of auditory stimulation with 750 or 8000 Hz tones, broadband noise, and silence. During periods of silence, tinnitus participants maintained increased hemodynamic responses in ROI, while a significant deactivation was seen in controls. Interestingly, non-ROI activity was also increased in the tinnitus group as compared to controls during silence. The present results demonstrate that both auditory and select nonauditory cortices have elevated hemodynamic activity in participants with tinnitus in the absence of an external auditory stimulus, a finding that may reflect basic science neural correlates of tinnitus that ultimately contribute to phantom sound perception.

  13. Optogenetic stimulation of a meso-scale human cortical model

    Science.gov (United States)

    Selvaraj, Prashanth; Szeri, Andrew; Sleigh, Jamie; Kirsch, Heidi

    2015-03-01

    Neurological phenomena like sleep and seizures depend not only on the activity of individual neurons, but on the dynamics of neuron populations as well. Meso-scale models of cortical activity provide a means to study neural dynamics at the level of neuron populations. Additionally, they offer a safe and economical way to test the effects and efficacy of stimulation techniques on the dynamics of the cortex. Here, we use a physiologically relevant meso-scale model of the cortex to study the hypersynchronous activity of neuron populations during epileptic seizures. The model consists of a set of stochastic, highly non-linear partial differential equations. Next, we use optogenetic stimulation to control seizures in a hyperexcited cortex, and to induce seizures in a normally functioning cortex. The high spatial and temporal resolution this method offers makes a strong case for the use of optogenetics in treating meso scale cortical disorders such as epileptic seizures. We use bifurcation analysis to investigate the effect of optogenetic stimulation in the meso scale model, and its efficacy in suppressing the non-linear dynamics of seizures.

  14. Four-dimensional maps of the human somatosensory system.

    Science.gov (United States)

    Avanzini, Pietro; Abdollahi, Rouhollah O; Sartori, Ivana; Caruana, Fausto; Pelliccia, Veronica; Casaceli, Giuseppe; Mai, Roberto; Lo Russo, Giorgio; Rizzolatti, Giacomo; Orban, Guy A

    2016-03-29

    A fine-grained description of the spatiotemporal dynamics of human brain activity is a major goal of neuroscientific research. Limitations in spatial and temporal resolution of available noninvasive recording and imaging techniques have hindered so far the acquisition of precise, comprehensive four-dimensional maps of human neural activity. The present study combines anatomical and functional data from intracerebral recordings of nearly 100 patients, to generate highly resolved four-dimensional maps of human cortical processing of nonpainful somatosensory stimuli. These maps indicate that the human somatosensory system devoted to the hand encompasses a widespread network covering more than 10% of the cortical surface of both hemispheres. This network includes phasic components, centered on primary somatosensory cortex and neighboring motor, premotor, and inferior parietal regions, and tonic components, centered on opercular and insular areas, and involving human parietal rostroventral area and ventral medial-superior-temporal area. The technique described opens new avenues for investigating the neural basis of all levels of cortical processing in humans.

  15. Neural Correlates of Indicators of Sound Change in Cantonese: Evidence from Cortical and Subcortical Processes.

    Science.gov (United States)

    Maggu, Akshay R; Liu, Fang; Antoniou, Mark; Wong, Patrick C M

    2016-01-01

    Across time, languages undergo changes in phonetic, syntactic, and semantic dimensions. Social, cognitive, and cultural factors contribute to sound change, a phenomenon in which the phonetics of a language undergo changes over time. Individuals who misperceive and produce speech in a slightly divergent manner (called innovators ) contribute to variability in the society, eventually leading to sound change. However, the cause of variability in these individuals is still unknown. In this study, we examined whether such misperceptions are represented in neural processes of the auditory system. We investigated behavioral, subcortical (via FFR), and cortical (via P300) manifestations of sound change processing in Cantonese, a Chinese language in which several lexical tones are merging. Across the merging categories, we observed a similar gradation of speech perception abilities in both behavior and the brain (subcortical and cortical processes). Further, we also found that behavioral evidence of tone merging correlated with subjects' encoding at the subcortical and cortical levels. These findings indicate that tone-merger categories, that are indicators of sound change in Cantonese, are represented neurophysiologically with high fidelity. Using our results, we speculate that innovators encode speech in a slightly deviant neurophysiological manner, and thus produce speech divergently that eventually spreads across the community and contributes to sound change.

  16. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. We differ from other animals in having direct cortical connections to spinal motoneurons, which bypass spinal...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...

  17. Prediction for human intelligence using morphometric characteristics of cortical surface: partial least square analysis.

    Science.gov (United States)

    Yang, J-J; Yoon, U; Yun, H J; Im, K; Choi, Y Y; Lee, K H; Park, H; Hough, M G; Lee, J-M

    2013-08-29

    A number of imaging studies have reported neuroanatomical correlates of human intelligence with various morphological characteristics of the cerebral cortex. However, it is not yet clear whether these morphological properties of the cerebral cortex account for human intelligence. We assumed that the complex structure of the cerebral cortex could be explained effectively considering cortical thickness, surface area, sulcal depth and absolute mean curvature together. In 78 young healthy adults (age range: 17-27, male/female: 39/39), we used the full-scale intelligence quotient (FSIQ) and the cortical measurements calculated in native space from each subject to determine how much combining various cortical measures explained human intelligence. Since each cortical measure is thought to be not independent but highly inter-related, we applied partial least square (PLS) regression, which is one of the most promising multivariate analysis approaches, to overcome multicollinearity among cortical measures. Our results showed that 30% of FSIQ was explained by the first latent variable extracted from PLS regression analysis. Although it is difficult to relate the first derived latent variable with specific anatomy, we found that cortical thickness measures had a substantial impact on the PLS model supporting the most significant factor accounting for FSIQ. Our results presented here strongly suggest that the new predictor combining different morphometric properties of complex cortical structure is well suited for predicting human intelligence. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Recognition of facial expressions by cortical multi-scale line and edge coding

    OpenAIRE

    Sousa, R.; Rodrigues, J. M. F.; du Buf, J. M. H.

    2010-01-01

    Face-to-face communications between humans involve emotions, which often are unconsciously conveyed by facial expressions and body gestures. Intelligent human-machine interfaces, for example in cognitive robotics, need to recognize emotions. This paper addresses facial expressions and their neural correlates on the basis of a model of the visual cortex: the multi-scale line and edge coding. The recognition model links the cortical representation with Paul Ekman's Action Units which are relate...

  19. Probing region-specific microstructure of human cortical areas using high angular and spatial resolution diffusion MRI.

    Science.gov (United States)

    Aggarwal, Manisha; Nauen, David W; Troncoso, Juan C; Mori, Susumu

    2015-01-15

    Regional heterogeneity in cortical cyto- and myeloarchitecture forms the structural basis of mapping of cortical areas in the human brain. In this study, we investigate the potential of diffusion MRI to probe the microstructure of cortical gray matter and its region-specific heterogeneity across cortical areas in the fixed human brain. High angular resolution diffusion imaging (HARDI) data at an isotropic resolution of 92-μm and 30 diffusion-encoding directions were acquired using a 3D diffusion-weighted gradient-and-spin-echo sequence, from prefrontal (Brodmann area 9), primary motor (area 4), primary somatosensory (area 3b), and primary visual (area 17) cortical specimens (n=3 each) from three human subjects. Further, the diffusion MR findings in these cortical areas were compared with histological silver impregnation of the same specimens, in order to investigate the underlying architectonic features that constitute the microstructural basis of diffusion-driven contrasts in cortical gray matter. Our data reveal distinct and region-specific diffusion MR contrasts across the studied areas, allowing delineation of intracortical bands of tangential fibers in specific layers-layer I, layer VI, and the inner and outer bands of Baillarger. The findings of this work demonstrate unique sensitivity of diffusion MRI to differentiate region-specific cortical microstructure in the human brain, and will be useful for myeloarchitectonic mapping of cortical areas as well as to achieve an understanding of the basis of diffusion NMR contrasts in cortical gray matter. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Neural mechanisms of social dominance

    Science.gov (United States)

    Watanabe, Noriya; Yamamoto, Miyuki

    2015-01-01

    In a group setting, individuals' perceptions of their own level of dominance or of the dominance level of others, and the ability to adequately control their behavior based on these perceptions are crucial for living within a social environment. Recent advances in neural imaging and molecular technology have enabled researchers to investigate the neural substrates that support the perception of social dominance and the formation of a social hierarchy in humans. At the systems' level, recent studies showed that dominance perception is represented in broad brain regions which include the amygdala, hippocampus, striatum, and various cortical networks such as the prefrontal, and parietal cortices. Additionally, neurotransmitter systems such as the dopaminergic and serotonergic systems, modulate and are modulated by the formation of the social hierarchy in a group. While these monoamine systems have a wide distribution and multiple functions, it was recently found that the Neuropeptide B/W contributes to the perception of dominance and is present in neurons that have a limited projection primarily to the amygdala. The present review discusses the specific roles of these neural regions and neurotransmitter systems in the perception of dominance and in hierarchy formation. PMID:26136644

  1. Neural mechanisms of social dominance

    Directory of Open Access Journals (Sweden)

    Noriya eWatanabe

    2015-06-01

    Full Text Available In a group setting, individuals’ perceptions of their own level of dominance or of the dominance level of others, and the ability to adequately control their behavior based on these perceptions are crucial for living within a social environment. Recent advances in neural imaging and molecular technology have enabled researchers to investigate the neural substrates that support the perception of social dominance and the formation of a social hierarchy in humans. At the systems’ level, recent studies showed that dominance perception is represented in broad brain regions which include the amygdala, hippocampus, striatum, and various cortical networks such as the prefrontal, and parietal cortices. Additionally, neurotransmitter systems such as the dopaminergic and serotonergic systems, modulate and are modulated by the formation of the social hierarchy in a group. While these monoamine systems have a wide distribution and multiple functions, it was recently found that the Neuropeptide B/W contributes to the perception of dominance and is present in neurons that have a limited projection primarily to the amygdala. The present review discusses the specific roles of these neural regions and neurotransmitter systems in the perception of dominance and in hierarchy formation.

  2. The participation of cortical amygdala in innate, odor-driven behavior

    Science.gov (United States)

    Root, Cory M.; Denny, Christine A.; Hen, René; Axel, Richard

    2014-01-01

    Innate behaviors are observed in naïve animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviors are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centers have been anatomically defined1-3 but the specific pathways responsible for innate responses to volatile odors have not been identified. We have devised genetic strategies that demonstrate that a stereotyped neural circuit that transmits information from the olfactory bulb to cortical amygdala is necessary for innate aversive and appetitive behaviors. Moreover, we have employed the promoter of the activity-dependent gene, arc, to express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odors that elicit innate behaviors. Optical activation of these neurons leads to appropriate behaviors that recapitulate the responses to innate odors. These data indicate that the cortical amygdala plays a critical role in the generation of innate odor-driven behaviors but do not preclude the participation of cortical amygdala in learned olfactory behaviors. PMID:25383519

  3. Human Auditory and Adjacent Nonauditory Cerebral Cortices Are Hypermetabolic in Tinnitus as Measured by Functional Near-Infrared Spectroscopy (fNIRS

    Directory of Open Access Journals (Sweden)

    Mohamad Issa

    2016-01-01

    Full Text Available Tinnitus is the phantom perception of sound in the absence of an acoustic stimulus. To date, the purported neural correlates of tinnitus from animal models have not been adequately characterized with translational technology in the human brain. The aim of the present study was to measure changes in oxy-hemoglobin concentration from regions of interest (ROI; auditory cortex and non-ROI (adjacent nonauditory cortices during auditory stimulation and silence in participants with subjective tinnitus appreciated equally in both ears and in nontinnitus controls using functional near-infrared spectroscopy (fNIRS. Control and tinnitus participants with normal/near-normal hearing were tested during a passive auditory task. Hemodynamic activity was monitored over ROI and non-ROI under episodic periods of auditory stimulation with 750 or 8000 Hz tones, broadband noise, and silence. During periods of silence, tinnitus participants maintained increased hemodynamic responses in ROI, while a significant deactivation was seen in controls. Interestingly, non-ROI activity was also increased in the tinnitus group as compared to controls during silence. The present results demonstrate that both auditory and select nonauditory cortices have elevated hemodynamic activity in participants with tinnitus in the absence of an external auditory stimulus, a finding that may reflect basic science neural correlates of tinnitus that ultimately contribute to phantom sound perception.

  4. Improved Discriminability of Spatiotemporal Neural Patterns in Rat Motor Cortical Areas as Directional Choice Learning Progresses

    Directory of Open Access Journals (Sweden)

    Hongwei eMao

    2015-03-01

    Full Text Available Animals learn to choose a proper action among alternatives to improve their odds of success in food foraging and other activities critical for survival. Through trial-and-error, they learn correct associations between their choices and external stimuli. While a neural network that underlies such learning process has been identified at a high level, it is still unclear how individual neurons and a neural ensemble adapt as learning progresses. In this study, we monitored the activity of single units in the rat medial and lateral agranular (AGm and AGl, respectively areas as rats learned to make a left or right side lever press in response to a left or right side light cue. We noticed that rat movement parameters during the performance of the directional choice task quickly became stereotyped during the first 2-3 days or sessions. But learning the directional choice problem took weeks to occur. Accompanying rats’ behavioral performance adaptation, we observed neural modulation by directional choice in recorded single units. Our analysis shows that ensemble mean firing rates in the cue-on period did not change significantly as learning progressed, and the ensemble mean rate difference between left and right side choices did not show a clear trend of change either. However, the spatiotemporal firing patterns of the neural ensemble exhibited improved discriminability between the two directional choices through learning. These results suggest a spatiotemporal neural coding scheme in a motor cortical neural ensemble that may be responsible for and contributing to learning the directional choice task.

  5. Motor Cortex and Motor Cortical Interhemispheric Communication in Walking After Stroke: The Roles of Transcranial Magnetic Stimulation and Animal Models in Our Current and Future Understanding.

    Science.gov (United States)

    Charalambous, Charalambos C; Bowden, Mark G; Adkins, DeAnna L

    2016-01-01

    Despite the plethora of human neurophysiological research, the bilateral involvement of the leg motor cortical areas and their interhemispheric interaction during both normal and impaired human walking is poorly understood. Using transcranial magnetic stimulation (TMS), we have expanded our understanding of the role upper-extremity motor cortical areas play in normal movements and how stroke alters this role, and probed the efficacy of interventions to improve post-stroke arm function. However, similar investigations of the legs have lagged behind, in part, due to the anatomical difficulty in using TMS to stimulate the leg motor cortical areas. Additionally, leg movements are predominately bilaterally controlled and require interlimb coordination that may involve both hemispheres. The sensitive, but invasive, tools used in animal models of locomotion hold great potential for increasing our understanding of the bihemispheric motor cortical control of walking. In this review, we discuss 3 themes associated with the bihemispheric motor cortical control of walking after stroke: (a) what is known about the role of the bihemispheric motor cortical control in healthy and poststroke leg movements, (b) how the neural remodeling of the contralesional hemisphere can affect walking recovery after a stroke, and (c) what is the effect of behavioral rehabilitation training of walking on the neural remodeling of the motor cortical areas bilaterally. For each theme, we discuss how rodent models can enhance the present knowledge on human walking by testing hypotheses that cannot be investigated in humans, and how these findings can then be back-translated into the neurorehabilitation of poststroke walking. © The Author(s) 2015.

  6. Higher cortical modulation of pain perception in the human brain: Psychological determinant.

    Science.gov (United States)

    Chen, Andrew Cn

    2009-10-01

    Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed determination, (b) distraction, (c) placebo, (d) hypnosis, (e) meditation, (f) qi-gong, (g) belief, and (h) emotions, respectively, in the brain function for pain modulation. In each, the operational definition, cortical processing, neuroimaging, and pain modulation were systematically deliberated. However, not all studies had featured the brain modulation processing but rather demonstrated potential effects on human pain. In our own studies on the emotional modulation on human pain, we observed that emotions could be induced from music melodies or pictures perception for reduction of tonic human pain, mainly in potentiation of the posterior alpha EEG fields, likely resulted from underneath activities of precuneous in regulation of consciousness, including pain perception. To sum, higher brain functions become the leading edge research in all sciences. How to solve the information bit of thinking and feeling in the brain can be the greatest challenge of human intelligence. Application of higher cortical modulation of human pain and suffering can lead to the progress of social humanity and civilization.

  7. A neural theory of visual attention

    DEFF Research Database (Denmark)

    Bundesen, Claus; Habekost, Thomas; Kyllingsbæk, Søren

    2005-01-01

    A neural theory of visual attention (NTVA) is presented. NTVA is a neural interpretation of C. Bundesen's (1990) theory of visual attention (TVA). In NTVA, visual processing capacity is distributed across stimuli by dynamic remapping of receptive fields of cortical cells such that more processing...... resources (cells) are devoted to behaviorally important objects than to less important ones. By use of the same basic equations used in TVA, NTVA accounts for a wide range of known attentional effects in human performance (reaction times and error rates) and a wide range of effects observed in firing rates...

  8. Differential neural network configuration during human path integration

    Science.gov (United States)

    Arnold, Aiden E. G. F; Burles, Ford; Bray, Signe; Levy, Richard M.; Iaria, Giuseppe

    2014-01-01

    Path integration is a fundamental skill for navigation in both humans and animals. Despite recent advances in unraveling the neural basis of path integration in animal models, relatively little is known about how path integration operates at a neural level in humans. Previous attempts to characterize the neural mechanisms used by humans to visually path integrate have suggested a central role of the hippocampus in allowing accurate performance, broadly resembling results from animal data. However, in recent years both the central role of the hippocampus and the perspective that animals and humans share similar neural mechanisms for path integration has come into question. The present study uses a data driven analysis to investigate the neural systems engaged during visual path integration in humans, allowing for an unbiased estimate of neural activity across the entire brain. Our results suggest that humans employ common task control, attention and spatial working memory systems across a frontoparietal network during path integration. However, individuals differed in how these systems are configured into functional networks. High performing individuals were found to more broadly express spatial working memory systems in prefrontal cortex, while low performing individuals engaged an allocentric memory system based primarily in the medial occipito-temporal region. These findings suggest that visual path integration in humans over short distances can operate through a spatial working memory system engaging primarily the prefrontal cortex and that the differential configuration of memory systems recruited by task control networks may help explain individual biases in spatial learning strategies. PMID:24808849

  9. Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth.

    Directory of Open Access Journals (Sweden)

    Olga Kapellou

    2006-08-01

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

  10. A novel neural prosthesis providing long-term electrocorticography recording and cortical stimulation for epilepsy and brain-computer interface.

    Science.gov (United States)

    Romanelli, Pantaleo; Piangerelli, Marco; Ratel, David; Gaude, Christophe; Costecalde, Thomas; Puttilli, Cosimo; Picciafuoco, Mauro; Benabid, Alim; Torres, Napoleon

    2018-05-11

    OBJECTIVE Wireless technology is a novel tool for the transmission of cortical signals. Wireless electrocorticography (ECoG) aims to improve the safety and diagnostic gain of procedures requiring invasive localization of seizure foci and also to provide long-term recording of brain activity for brain-computer interfaces (BCIs). However, no wireless devices aimed at these clinical applications are currently available. The authors present the application of a fully implantable and externally rechargeable neural prosthesis providing wireless ECoG recording and direct cortical stimulation (DCS). Prolonged wireless ECoG monitoring was tested in nonhuman primates by using a custom-made device (the ECoG implantable wireless 16-electrode [ECOGIW-16E] device) containing a 16-contact subdural grid. This is a preliminary step toward large-scale, long-term wireless ECoG recording in humans. METHODS The authors implanted the ECOGIW-16E device over the left sensorimotor cortex of a nonhuman primate ( Macaca fascicularis), recording ECoG signals over a time span of 6 months. Daily electrode impedances were measured, aiming to maintain the impedance values below a threshold of 100 KΩ. Brain mapping was obtained through wireless cortical stimulation at fixed intervals (1, 3, and 6 months). After 6 months, the device was removed. The authors analyzed cortical tissues by using conventional histological and immunohistological investigation to assess whether there was evidence of damage after the long-term implantation of the grid. RESULTS The implant was well tolerated; no neurological or behavioral consequences were reported in the monkey, which resumed his normal activities within a few hours of the procedure. The signal quality of wireless ECoG remained excellent over the 6-month observation period. Impedance values remained well below the threshold value; the average impedance per contact remains approximately 40 KΩ. Wireless cortical stimulation induced movements of the upper

  11. Dissociable neural response signatures for slow amplitude and frequency modulation in human auditory cortex.

    Science.gov (United States)

    Henry, Molly J; Obleser, Jonas

    2013-01-01

    Natural auditory stimuli are characterized by slow fluctuations in amplitude and frequency. However, the degree to which the neural responses to slow amplitude modulation (AM) and frequency modulation (FM) are capable of conveying independent time-varying information, particularly with respect to speech communication, is unclear. In the current electroencephalography (EEG) study, participants listened to amplitude- and frequency-modulated narrow-band noises with a 3-Hz modulation rate, and the resulting neural responses were compared. Spectral analyses revealed similar spectral amplitude peaks for AM and FM at the stimulation frequency (3 Hz), but amplitude at the second harmonic frequency (6 Hz) was much higher for FM than for AM. Moreover, the phase delay of neural responses with respect to the full-band stimulus envelope was shorter for FM than for AM. Finally, the critical analysis involved classification of single trials as being in response to either AM or FM based on either phase or amplitude information. Time-varying phase, but not amplitude, was sufficient to accurately classify AM and FM stimuli based on single-trial neural responses. Taken together, the current results support the dissociable nature of cortical signatures of slow AM and FM. These cortical signatures potentially provide an efficient means to dissect simultaneously communicated slow temporal and spectral information in acoustic communication signals.

  12. K -shell decomposition reveals hierarchical cortical organization of the human brain

    International Nuclear Information System (INIS)

    Lahav, Nir; Ksherim, Baruch; Havlin, Shlomo; Ben-Simon, Eti; Maron-Katz, Adi; Cohen, Reuven

    2016-01-01

    In recent years numerous attempts to understand the human brain were undertaken from a network point of view. A network framework takes into account the relationships between the different parts of the system and enables to examine how global and complex functions might emerge from network topology. Previous work revealed that the human brain features ‘small world’ characteristics and that cortical hubs tend to interconnect among themselves. However, in order to fully understand the topological structure of hubs, and how their profile reflect the brain’s global functional organization, one needs to go beyond the properties of a specific hub and examine the various structural layers that make up the network. To address this topic further, we applied an analysis known in statistical physics and network theory as k-shell decomposition analysis. The analysis was applied on a human cortical network, derived from MRI/DSI data of six participants. Such analysis enables us to portray a detailed account of cortical connectivity focusing on different neighborhoods of inter-connected layers across the cortex. Our findings reveal that the human cortex is highly connected and efficient, and unlike the internet network contains no isolated nodes. The cortical network is comprised of a nucleus alongside shells of increasing connectivity that formed one connected giant component, revealing the human brain’s global functional organization. All these components were further categorized into three hierarchies in accordance with their connectivity profile, with each hierarchy reflecting different functional roles. Such a model may explain an efficient flow of information from the lowest hierarchy to the highest one, with each step enabling increased data integration. At the top, the highest hierarchy (the nucleus) serves as a global interconnected collective and demonstrates high correlation with consciousness related regions, suggesting that the nucleus might serve as a

  13. Viability of dielectrophoretically trapped neuronal cortical cells in culture

    NARCIS (Netherlands)

    Heida, Tjitske; Vulto, P; Rutten, Wim; Marani, Enrico

    2001-01-01

    Negative dielectrophoretic trapping of neural cells is an efficient way to position neural cells on the electrode sites of planar micro-electrode arrays. The preservation of viability of the neural cells is essential for this approach. This study investigates the viability of postnatal cortical rat

  14. Multiscale approach including microfibril scale to assess elastic constants of cortical bone based on neural network computation and homogenization method.

    Science.gov (United States)

    Barkaoui, Abdelwahed; Chamekh, Abdessalem; Merzouki, Tarek; Hambli, Ridha; Mkaddem, Ali

    2014-03-01

    The complexity and heterogeneity of bone tissue require a multiscale modeling to understand its mechanical behavior and its remodeling mechanisms. In this paper, a novel multiscale hierarchical approach including microfibril scale based on hybrid neural network (NN) computation and homogenization equations was developed to link nanoscopic and macroscopic scales to estimate the elastic properties of human cortical bone. The multiscale model is divided into three main phases: (i) in step 0, the elastic constants of collagen-water and mineral-water composites are calculated by averaging the upper and lower Hill bounds; (ii) in step 1, the elastic properties of the collagen microfibril are computed using a trained NN simulation. Finite element calculation is performed at nanoscopic levels to provide a database to train an in-house NN program; and (iii) in steps 2-10 from fibril to continuum cortical bone tissue, homogenization equations are used to perform the computation at the higher scales. The NN outputs (elastic properties of the microfibril) are used as inputs for the homogenization computation to determine the properties of mineralized collagen fibril. The mechanical and geometrical properties of bone constituents (mineral, collagen, and cross-links) as well as the porosity were taken in consideration. This paper aims to predict analytically the effective elastic constants of cortical bone by modeling its elastic response at these different scales, ranging from the nanostructural to mesostructural levels. Our findings of the lowest scale's output were well integrated with the other higher levels and serve as inputs for the next higher scale modeling. Good agreement was obtained between our predicted results and literature data. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Dissecting human cerebral organoids and fetal neocortex using single-cell RNAseq

    Science.gov (United States)

    Treutlein, Barbara

    Cerebral organoids - three-dimensional cultures of human cerebral tissue derived from pluripotent stem cells - have emerged as models of human cortical development. However, the extent to which in vitro organoid systems recapitulate neural progenitor cell proliferation and neuronal differentiation programs observed in vivo remains unclear. Here we use single-cell RNA sequencing (scRNA-seq) to dissect and compare cell composition and progenitor-to-neuron lineage relationships in human cerebral organoids and fetal neocortex. Covariation network analysis using the fetal neocortex data reveals known and novel interactions among genes central to neural progenitor proliferation and neuronal differentiation. In the organoid, we detect diverse progenitors and differentiated cell types of neuronal and mesenchymal lineages, and identify cells that derived from regions resembling the fetal neocortex. We find that these organoid cortical cells use gene expression programs remarkably similar to those of the fetal tissue in order to organize into cerebral cortex-like regions. Our comparison of in vivo and in vitro cortical single cell transcriptomes illuminates the genetic features underlying human cortical development that can be studied in organoid cultures.

  16. Human oocyte cryopreservation and the fate of cortical granules.

    Science.gov (United States)

    Ghetler, Yehudith; Skutelsky, Ehud; Ben Nun, Isaac; Ben Dor, Liah; Amihai, Dina; Shalgi, Ruth

    2006-07-01

    To examine the effect of the commonly used oocyte cryopreservation protocol on the cortical granules (CGs) of human immature germinal vesicle (GV) and mature metaphase II (MII) oocytes. Laboratory study. IVF unit. Unfertilized, intracytoplasmic sperm injected (ICSI) oocytes, and immature oocytes were cryopreserved using a slow freezing-rapid thawing program with 1,2-propanediol (PROH) as a cryoprotectant. Cortical granule exocytosis (CGE) was assessed by either confocal microscopy or transmission electron microscopy (TEM). The survival rates of frozen-thawed oocytes (mature and immature) were significantly lower compared with zygotes. Both mature and immature oocytes exhibited increased fluorescence after cryopreservation, indicating the occurrence of CGE. Mere exposure of oocytes to cryoprotectants induced CGE of 70% the value of control zygotes. The TEM revealed a drastic reduction in the amount of CGs at the cortex of frozen-thawed GV and MII oocytes, as well as appearance of vesicles in the ooplasm. The commonly used PROH freezing protocol for human oocytes resulted in extensive CGE. This finding explains why ICSI is needed to achieve fertilization of frozen-thawed human oocytes.

  17. Neural substrates of decision-making.

    Science.gov (United States)

    Broche-Pérez, Y; Herrera Jiménez, L F; Omar-Martínez, E

    2016-06-01

    Decision-making is the process of selecting a course of action from among 2 or more alternatives by considering the potential outcomes of selecting each option and estimating its consequences in the short, medium and long term. The prefrontal cortex (PFC) has traditionally been considered the key neural structure in decision-making process. However, new studies support the hypothesis that describes a complex neural network including both cortical and subcortical structures. The aim of this review is to summarise evidence on the anatomical structures underlying the decision-making process, considering new findings that support the existence of a complex neural network that gives rise to this complex neuropsychological process. Current evidence shows that the cortical structures involved in decision-making include the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). This process is assisted by subcortical structures including the amygdala, thalamus, and cerebellum. Findings to date show that both cortical and subcortical brain regions contribute to the decision-making process. The neural basis of decision-making is a complex neural network of cortico-cortical and cortico-subcortical connections which includes subareas of the PFC, limbic structures, and the cerebellum. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  18. Electrophysiological Data and the Biophysical Modelling of Local Cortical Circuits

    Directory of Open Access Journals (Sweden)

    Dimitris Pinotsis

    2014-03-01

    Full Text Available This paper shows how recordings of gamma oscillations – under different experimental conditions or from different subjects – can be combined with a class of population models called neural fields and dynamic causal modeling (DCM to distinguish among alternative hypotheses regarding cortical structure and function. This approach exploits inter-subject variability and trial-specific effects associated with modulations in the peak frequency of gamma oscillations. It draws on the computational power of Bayesian model inversion, when applied to neural field models of cortical dynamics. Bayesian model comparison allows one to adjudicate among different mechanistic hypotheses about cortical excitability, synaptic kinetics and the cardinal topographic features of local cortical circuits. It also provides optimal parameter estimates that quantify neuromodulation and the spatial dispersion of axonal connections or summation of receptive fields in the visual cortex. This paper provides an overview of a family of neural field models that have been recently implemented using the DCM toolbox of the academic freeware Statistical Parametric Mapping (SPM. The SPM software is a popular platform for analyzing neuroimaging data, used by several neuroscience communities worldwide. DCM allows for a formal (Bayesian statistical analysis of cortical network connectivity, based upon realistic biophysical models of brain responses. It is this particular feature of DCM – the unique combination of generative models with optimization techniques based upon (variational Bayesian principles – that furnishes a novel way to characterize functional brain architectures. In particular, it provides answers to questions about how the brain is wired and how it responds to different experimental manipulations. For a review of the general role of neural fields in SPM the reader can consult e.g. see [1]. Neural fields have a long and illustrious history in mathematical

  19. A novel cortical target to enhance hand motor output in humans with spinal cord injury.

    Science.gov (United States)

    Long, Jinyi; Federico, Paolo; Perez, Monica A

    2017-06-01

    A main goal of rehabilitation strategies in humans with spinal cord injury is to strengthen transmission in spared neural networks. Although neuromodulatory strategies have targeted different sites within the central nervous system to restore motor function following spinal cord injury, the role of cortical targets remain poorly understood. Here, we use 180 pairs of transcranial magnetic stimulation for ∼30 min over the hand representation of the motor cortex at an interstimulus interval mimicking the rhythmicity of descending late indirect (I) waves in corticospinal neurons (4.3 ms; I-wave protocol) or at an interstimulus interval in-between I-waves (3.5 ms; control protocol) on separate days in a randomized order. Late I-waves are thought to arise from trans-synaptic cortical inputs and have a crucial role in the recruitment of spinal motor neurons following spinal cord injury. Motor evoked potentials elicited by transcranial magnetic stimulation, paired-pulse intracortical inhibition, spinal motor neuron excitability (F-waves), index finger abduction force and electromyographic activity as well as a hand dexterity task were measured before and after both protocols in 15 individuals with chronic incomplete cervical spinal cord injury and 17 uninjured participants. We found that motor evoked potentials size increased in spinal cord injury and uninjured participants after the I-wave but not the control protocol for ∼30 to 60 min after the stimulation. Intracortical inhibition decreased and F-wave amplitude and persistence increased after the I-wave but not the control protocol, suggesting that cortical and subcortical networks contributed to changes in corticospinal excitability. Importantly, hand motor output and hand dexterity increased in individuals with spinal cord injury after the I-wave protocol. These results provide the first evidence that late synaptic input to corticospinal neurons may represent a novel therapeutic target for improving motor function

  20. Neural correlates of mirth and laughter: a direct electrical cortical stimulation study.

    Science.gov (United States)

    Yamao, Yukihiro; Matsumoto, Riki; Kunieda, Takeharu; Shibata, Sumiya; Shimotake, Akihiro; Kikuchi, Takayuki; Satow, Takeshi; Mikuni, Nobuhiro; Fukuyama, Hidenao; Ikeda, Akio; Miyamoto, Susumu

    2015-05-01

    Laughter consists of both motor and emotional aspects. The emotional component, known as mirth, is usually associated with the motor component, namely, bilateral facial movements. Previous electrical cortical stimulation (ES) studies revealed that mirth was associated with the basal temporal cortex, inferior frontal cortex, and medial frontal cortex. Functional neuroimaging implicated a role for the left inferior frontal and bilateral temporal cortices in humor processing. However, the neural origins and pathways linking mirth with facial movements are still unclear. We hereby report two cases with temporal lobe epilepsy undergoing subdural electrode implantation in whom ES of the left basal temporal cortex elicited both mirth and laughter-related facial muscle movements. In one case with normal hippocampus, high-frequency ES consistently caused contralateral facial movement, followed by bilateral facial movements with mirth. In contrast, in another case with hippocampal sclerosis (HS), ES elicited only mirth at low intensity and short duration, and eventually laughter at higher intensity and longer duration. In both cases, the basal temporal language area (BTLA) was located within or adjacent to the cortex where ES produced mirth. In conclusion, the present direct ES study demonstrated that 1) mirth had a close relationship with language function, 2) intact mesial temporal structures were actively engaged in the beginning of facial movements associated with mirth, and 3) these emotion-related facial movements had contralateral dominance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. File list: ALL.Neu.50.AllAg.Cortical_neuron [Chip-atlas[Archive

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  5. Restoring cortical control of functional movement in a human with quadriplegia.

    Science.gov (United States)

    Bouton, Chad E; Shaikhouni, Ammar; Annetta, Nicholas V; Bockbrader, Marcia A; Friedenberg, David A; Nielson, Dylan M; Sharma, Gaurav; Sederberg, Per B; Glenn, Bradley C; Mysiw, W Jerry; Morgan, Austin G; Deogaonkar, Milind; Rezai, Ali R

    2016-05-12

    Millions of people worldwide suffer from diseases that lead to paralysis through disruption of signal pathways between the brain and the muscles. Neuroprosthetic devices are designed to restore lost function and could be used to form an electronic 'neural bypass' to circumvent disconnected pathways in the nervous system. It has previously been shown that intracortically recorded signals can be decoded to extract information related to motion, allowing non-human primates and paralysed humans to control computers and robotic arms through imagined movements. In non-human primates, these types of signal have also been used to drive activation of chemically paralysed arm muscles. Here we show that intracortically recorded signals can be linked in real-time to muscle activation to restore movement in a paralysed human. We used a chronically implanted intracortical microelectrode array to record multiunit activity from the motor cortex in a study participant with quadriplegia from cervical spinal cord injury. We applied machine-learning algorithms to decode the neuronal activity and control activation of the participant's forearm muscles through a custom-built high-resolution neuromuscular electrical stimulation system. The system provided isolated finger movements and the participant achieved continuous cortical control of six different wrist and hand motions. Furthermore, he was able to use the system to complete functional tasks relevant to daily living. Clinical assessment showed that, when using the system, his motor impairment improved from the fifth to the sixth cervical (C5-C6) to the seventh cervical to first thoracic (C7-T1) level unilaterally, conferring on him the critical abilities to grasp, manipulate, and release objects. This is the first demonstration to our knowledge of successful control of muscle activation using intracortically recorded signals in a paralysed human. These results have significant implications in advancing neuroprosthetic technology

  6. Functional neural substrates of posterior cortical atrophy patients.

    Science.gov (United States)

    Shames, H; Raz, N; Levin, Netta

    2015-07-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome in which the most pronounced pathologic involvement is in the occipito-parietal visual regions. Herein, we aimed to better define the cortical reflection of this unique syndrome using a thorough battery of behavioral and functional MRI (fMRI) tests. Eight PCA patients underwent extensive testing to map their visual deficits. Assessments included visual functions associated with lower and higher components of the cortical hierarchy, as well as dorsal- and ventral-related cortical functions. fMRI was performed on five patients to examine the neuronal substrate of their visual functions. The PCA patient cohort exhibited stereopsis, saccadic eye movements and higher dorsal stream-related functional impairments, including simultant perception, image orientation, figure-from-ground segregation, closure and spatial orientation. In accordance with the behavioral findings, fMRI revealed intact activation in the ventral visual regions of face and object perception while more dorsal aspects of perception, including motion and gestalt perception, revealed impaired patterns of activity. In most of the patients, there was a lack of activity in the word form area, which is known to be linked to reading disorders. Finally, there was evidence of reduced cortical representation of the peripheral visual field, corresponding to the behaviorally assessed peripheral visual deficit. The findings are discussed in the context of networks extending from parietal regions, which mediate navigationally related processing, visually guided actions, eye movement control and working memory, suggesting that damage to these networks might explain the wide range of deficits in PCA patients.

  7. Recording human cortical population spikes non-invasively--An EEG tutorial.

    Science.gov (United States)

    Waterstraat, Gunnar; Fedele, Tommaso; Burghoff, Martin; Scheer, Hans-Jürgen; Curio, Gabriel

    2015-07-30

    Non-invasively recorded somatosensory high-frequency oscillations (sHFOs) evoked by electric nerve stimulation are markers of human cortical population spikes. Previously, their analysis was based on massive averaging of EEG responses. Advanced neurotechnology and optimized off-line analysis can enhance the signal-to-noise ratio of sHFOs, eventually enabling single-trial analysis. The rationale for developing dedicated low-noise EEG technology for sHFOs is unfolded. Detailed recording procedures and tailored analysis principles are explained step-by-step. Source codes in Matlab and Python are provided as supplementary material online. Combining synergistic hardware and analysis improvements, evoked sHFOs at around 600 Hz ('σ-bursts') can be studied in single-trials. Additionally, optimized spatial filters increase the signal-to-noise ratio of components at about 1 kHz ('κ-bursts') enabling their detection in non-invasive surface EEG. sHFOs offer a unique possibility to record evoked human cortical population spikes non-invasively. The experimental approaches and algorithms presented here enable also non-specialized EEG laboratories to combine measurements of conventional low-frequency EEG with the analysis of concomitant cortical population spike responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Understanding the Implications of Neural Population Activity on Behavior

    Science.gov (United States)

    Briguglio, John

    Learning how neural activity in the brain leads to the behavior we exhibit is one of the fundamental questions in Neuroscience. In this dissertation, several lines of work are presented to that use principles of neural coding to understand behavior. In one line of work, we formulate the efficient coding hypothesis in a non-traditional manner in order to test human perceptual sensitivity to complex visual textures. We find a striking agreement between how variable a particular texture signal is and how sensitive humans are to its presence. This reveals that the efficient coding hypothesis is still a guiding principle for neural organization beyond the sensory periphery, and that the nature of cortical constraints differs from the peripheral counterpart. In another line of work, we relate frequency discrimination acuity to neural responses from auditory cortex in mice. It has been previously observed that optogenetic manipulation of auditory cortex, in addition to changing neural responses, evokes changes in behavioral frequency discrimination. We are able to account for changes in frequency discrimination acuity on an individual basis by examining the Fisher information from the neural population with and without optogenetic manipulation. In the third line of work, we address the question of what a neural population should encode given that its inputs are responses from another group of neurons. Drawing inspiration from techniques in machine learning, we train Deep Belief Networks on fake retinal data and show the emergence of Garbor-like filters, reminiscent of responses in primary visual cortex. In the last line of work, we model the state of a cortical excitatory-inhibitory network during complex adaptive stimuli. Using a rate model with Wilson-Cowan dynamics, we demonstrate that simple non-linearities in the signal transferred from inhibitory to excitatory neurons can account for real neural recordings taken from auditory cortex. This work establishes and tests

  9. Prefrontal cortex and sensory cortices during working memory: quantity and quality.

    Science.gov (United States)

    Ku, Yixuan; Bodner, Mark; Zhou, Yong-Di

    2015-04-01

    The activity in sensory cortices and the prefrontal cortex (PFC) throughout the delay interval of working memory (WM) tasks reflect two aspects of WM-quality and quantity, respectively. The delay activity in sensory cortices is fine-tuned to sensory information and forms the neural basis of the precision of WM storage, while the delay activity in the PFC appears to represent behavioral goals and filters out irrelevant distractions, forming the neural basis of the quantity of task-relevant information in WM. The PFC and sensory cortices interact through different frequency bands of neuronal oscillation (theta, alpha, and gamma) to fulfill goal-directed behaviors.

  10. File list: Oth.Neu.10.AllAg.Cortical_neuron [Chip-atlas[Archive

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  13. File list: Oth.Neu.05.AllAg.Cortical_neuron [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. Neural basis of preference for human social hierarchy versus egalitarianism.

    Science.gov (United States)

    Chiao, Joan Y; Mathur, Vani A; Harada, Tokiko; Lipke, Trixie

    2009-06-01

    A fundamental way that individuals differ is in the degree to which they prefer social dominance hierarchy over egalitarianism as a guiding principle of societal structure, a phenomenon known as social dominance orientation. Here we show that preference for hierarchical rather than egalitarian social relations varies as a function of neural responses within left anterior insula and anterior cingulate cortices. Our findings provide novel evidence that preference for social dominance hierarchy is associated with neural functioning within brain regions that are associated with the ability to share and feel concern for the pain of others; this suggests a neurobiological basis for social and political attitudes. Implications of these findings for research on the social neuroscience of fairness, justice, and intergroup relations are discussed.

  15. Nonlinear dynamics of cortical responses to color in the human cVEP.

    Science.gov (United States)

    Nunez, Valerie; Shapley, Robert M; Gordon, James

    2017-09-01

    The main finding of this paper is that the human visual cortex responds in a very nonlinear manner to the color contrast of pure color patterns. We examined human cortical responses to color checkerboard patterns at many color contrasts, measuring the chromatic visual evoked potential (cVEP) with a dense electrode array. Cortical topography of the cVEPs showed that they were localized near the posterior electrode at position Oz, indicating that the primary cortex (V1) was the major source of responses. The choice of fine spatial patterns as stimuli caused the cVEP response to be driven by double-opponent neurons in V1. The cVEP waveform revealed nonlinear color signal processing in the V1 cortex. The cVEP time-to-peak decreased and the waveform's shape was markedly narrower with increasing cone contrast. Comparison of the linear dynamics of retinal and lateral geniculate nucleus responses with the nonlinear dynamics of the cortical cVEP indicated that the nonlinear dynamics originated in the V1 cortex. The nature of the nonlinearity is a kind of automatic gain control that adjusts cortical dynamics to be faster when color contrast is greater.

  16. Neural networks for perception human and machine perception

    CERN Document Server

    Wechsler, Harry

    1991-01-01

    Neural Networks for Perception, Volume 1: Human and Machine Perception focuses on models for understanding human perception in terms of distributed computation and examples of PDP models for machine perception. This book addresses both theoretical and practical issues related to the feasibility of both explaining human perception and implementing machine perception in terms of neural network models. The book is organized into two parts. The first part focuses on human perception. Topics on network model ofobject recognition in human vision, the self-organization of functional architecture in t

  17. Cortical Network Dynamics of Perceptual Decision-Making in the Human Brain

    Directory of Open Access Journals (Sweden)

    Markus eSiegel

    2011-02-01

    Full Text Available Goal-directed behavior requires the flexible transformation of sensory evidence about our environment into motor actions. Studies of perceptual decision-making have shown that this transformation is distributed across several widely separated brain regions. Yet, little is known about how decision-making emerges from the dynamic interactions among these regions. Here, we review a series of studies, in which we characterized the cortical network interactions underlying a perceptual decision process in the human brain. We used magnetoencephalography (MEG to measure the large-scale cortical population dynamics underlying each of the sub-processes involved in this decision: the encoding of sensory evidence and action plan, the mapping between the two, and the attentional selection of task-relevant evidence. We found that these sub-processes are mediated by neuronal oscillations within specific frequency ranges. Localized gamma-band oscillations in sensory and motor cortices reflect the encoding of the sensory evidence and motor plan. Large-scale oscillations across widespread cortical networks mediate the integrative processes connecting these local networks: Gamma- and beta-band oscillations across frontal, parietal and sensory cortices serve the selection of relevant sensory evidence and its flexible mapping onto action plans. In sum, our results suggest that perceptual decisions are mediated by oscillatory interactions within overlapping local and large-scale cortical networks.

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  1. File list: Pol.Neu.50.AllAg.Cortical_neuron [Chip-atlas[Archive

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  2. Stroke rehabilitation using noninvasive cortical stimulation: aphasia.

    Science.gov (United States)

    Mylius, Veit; Zouari, Hela G; Ayache, Samar S; Farhat, Wassim H; Lefaucheur, Jean-Pascal

    2012-08-01

    Poststroke aphasia results from the lesion of cortical areas involved in the motor production of speech (Broca's aphasia) or in the semantic aspects of language comprehension (Wernicke's aphasia). Such lesions produce an important reorganization of speech/language-specific brain networks due to an imbalance between cortical facilitation and inhibition. In fact, functional recovery is associated with changes in the excitability of the damaged neural structures and their connections. Two main mechanisms are involved in poststroke aphasia recovery: the recruitment of perilesional regions of the left hemisphere in case of small lesion and the acquisition of language processing ability in homotopic areas of the nondominant right hemisphere when left hemispheric language abilities are permanently lost. There is some evidence that noninvasive cortical stimulation, especially when combined with language therapy or other therapeutic approaches, can promote aphasia recovery. Cortical stimulation was mainly used to either increase perilesional excitability or reduce contralesional activity based on the concept of reciprocal inhibition and maladaptive plasticity. However, recent studies also showed some positive effects of the reinforcement of neural activities in the contralateral right hemisphere, based on the potential compensatory role of the nondominant hemisphere in stroke recovery.

  3. Single-site neural tube closure in human embryos revisited.

    Science.gov (United States)

    de Bakker, Bernadette S; Driessen, Stan; Boukens, Bastiaan J D; van den Hoff, Maurice J B; Oostra, Roelof-Jan

    2017-10-01

    Since the multi-site closure theory was first proposed in 1991 as explanation for the preferential localizations of neural tube defects, the closure of the neural tube has been debated. Although the multi-site closure theory is much cited in clinical literature, single-site closure is most apparent in literature concerning embryology. Inspired by Victor Hamburgers (1900-2001) statement that "our real teacher has been and still is the embryo, who is, incidentally, the only teacher who is always right", we decided to critically review both theories of neural tube closure. To verify the theories of closure, we studied serial histological sections of 10 mouse embryos between 8.5 and 9.5 days of gestation and 18 human embryos of the Carnegie collection between Carnegie stage 9 (19-21 days) and 13 (28-32 days). Neural tube closure was histologically defined by the neuroepithelial remodeling of the two adjoining neural fold tips in the midline. We did not observe multiple fusion sites in neither mouse nor human embryos. A meta-analysis of case reports on neural tube defects showed that defects can occur at any level of the neural axis. Our data indicate that the human neural tube fuses at a single site and, therefore, we propose to reinstate the single-site closure theory for neural tube closure. We showed that neural tube defects are not restricted to a specific location, thereby refuting the reasoning underlying the multi-site closure theory. Clin. Anat. 30:988-999, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Engineering Human Neural Tissue by 3D Bioprinting.

    Science.gov (United States)

    Gu, Qi; Tomaskovic-Crook, Eva; Wallace, Gordon G; Crook, Jeremy M

    2018-01-01

    Bioprinting provides an opportunity to produce three-dimensional (3D) tissues for biomedical research and translational drug discovery, toxicology, and tissue replacement. Here we describe a method for fabricating human neural tissue by 3D printing human neural stem cells with a bioink, and subsequent gelation of the bioink for cell encapsulation, support, and differentiation to functional neurons and supporting neuroglia. The bioink uniquely comprises the polysaccharides alginate, water-soluble carboxymethyl-chitosan, and agarose. Importantly, the method could be adapted to fabricate neural and nonneural tissues from other cell types, with the potential to be applied for both research and clinical product development.

  5. An RNA gene expressed during cortical development evolved rapidly in humans

    DEFF Research Database (Denmark)

    Pollard, Katherine S; Salama, Sofie R; Lambert, Nelle

    2006-01-01

    in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal-Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other...

  6. Using modern human cortical bone distribution to test the systemic robusticity hypothesis.

    Science.gov (United States)

    Baab, Karen L; Copes, Lynn E; Ward, Devin L; Wells, Nora; Grine, Frederick E

    2018-06-01

    The systemic robusticity hypothesis links the thickness of cortical bone in both the cranium and limb bones. This hypothesis posits that thick cortical bone is in part a systemic response to circulating hormones, such as growth hormone and thyroid hormone, possibly related to physical activity or cold climates. Although this hypothesis has gained popular traction, only rarely has robusticity of the cranium and postcranial skeleton been considered jointly. We acquired computed tomographic scans from associated crania, femora and humeri from single individuals representing 11 populations in Africa and North America (n = 228). Cortical thickness in the parietal, frontal and occipital bones and cortical bone area in limb bone diaphyses were analyzed using correlation, multiple regression and general linear models to test the hypothesis. Absolute thickness values from the crania were not correlated with cortical bone area of the femur or humerus, which is at odds with the systemic robusticity hypothesis. However, measures of cortical bone scaled by total vault thickness and limb cross-sectional area were positively correlated between the cranium and postcranium. When accounting for a range of potential confounding variables, including sex, age and body mass, variation in relative postcranial cortical bone area explained ∼20% of variation in the proportion of cortical cranial bone thickness. While these findings provide limited support for the systemic robusticity hypothesis, cranial cortical thickness did not track climate or physical activity across populations. Thus, some of the variation in cranial cortical bone thickness in modern humans is attributable to systemic effects, but the driving force behind this effect remains obscure. Moreover, neither absolute nor proportional measures of cranial cortical bone thickness are positively correlated with total cranial bone thickness, complicating the extrapolation of these findings to extinct species where only cranial

  7. 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

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  11. File list: InP.Neu.50.AllAg.Cortical_neuron [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. A human neurodevelopmental model for Williams syndrome.

    Science.gov (United States)

    Chailangkarn, Thanathom; Trujillo, Cleber A; Freitas, Beatriz C; Hrvoj-Mihic, Branka; Herai, Roberto H; Yu, Diana X; Brown, Timothy T; Marchetto, Maria C; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M Colin; Hanson, Kari L; Romero, Sarah; Jacobs, Bob; Dale, Anders M; Dai, Li; Korenberg, Julie R; Gage, Fred H; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R

    2016-08-18

    Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

  13. Effects of Parecoxib and Fentanyl on nociception-induced cortical activity

    Directory of Open Access Journals (Sweden)

    Wang Ying-Wei

    2010-01-01

    Full Text Available Abstract Background Analgesics, including opioids and non-steroid anti-inflammatory drugs reduce postoperative pain. However, little is known about the quantitative effects of these drugs on cortical activity induced by nociceptive stimulation. The aim of the present study was to determine the neural activity in response to a nociceptive stimulus and to investigate the effects of fentanyl (an opioid agonist and parecoxib (a selective cyclooxygenase-2 inhibitor on this nociception-induced cortical activity evoked by tail pinch. Extracellular recordings (electroencephalogram and multi-unit signals were performed in the area of the anterior cingulate cortex while intracellular recordings were made in the primary somatosensory cortex. The effects of parecoxib and fentanyl on induced cortical activity were compared. Results Peripheral nociceptive stimulation in anesthetized rats produced an immediate electroencephalogram (EEG desynchronization resembling the cortical arousal (low-amplitude, fast-wave activity, while the membrane potential switched into a persistent depolarization state. The induced cortical activity was abolished by fentanyl, and the fentanyl's effect was reversed by the opioid receptor antagonist, naloxone. Parecoxib, on the other hand, did not significantly affect the neural activity. Conclusion Cortical activity was modulated by nociceptive stimulation in anesthetized rats. Fentanyl showed a strong inhibitory effect on the nociceptive-stimulus induced cortical activity while parecoxib had no significant effect.

  14. 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.

  15. The developing human connectome project: A minimal processing pipeline for neonatal cortical surface reconstruction.

    Science.gov (United States)

    Makropoulos, Antonios; Robinson, Emma C; Schuh, Andreas; Wright, Robert; Fitzgibbon, Sean; Bozek, Jelena; Counsell, Serena J; Steinweg, Johannes; Vecchiato, Katy; Passerat-Palmbach, Jonathan; Lenz, Gregor; Mortari, Filippo; Tenev, Tencho; Duff, Eugene P; Bastiani, Matteo; Cordero-Grande, Lucilio; Hughes, Emer; Tusor, Nora; Tournier, Jacques-Donald; Hutter, Jana; Price, Anthony N; Teixeira, Rui Pedro A G; Murgasova, Maria; Victor, Suresh; Kelly, Christopher; Rutherford, Mary A; Smith, Stephen M; Edwards, A David; Hajnal, Joseph V; Jenkinson, Mark; Rueckert, Daniel

    2018-06-01

    The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines. In this paper, we propose a fully automated processing pipeline for the structural Magnetic Resonance Imaging (MRI) of the developing neonatal brain. This proposed pipeline consists of a refined framework for cortical and sub-cortical volume segmentation, cortical surface extraction, and cortical surface inflation, which has been specifically designed to address considerable differences between adult and neonatal brains, as imaged using MRI. Using the proposed pipeline our results demonstrate that images collected from 465 subjects ranging from 28 to 45 weeks post-menstrual age (PMA) can be processed fully automatically; generating cortical surface models that are topologically correct, and correspond well with manual evaluations of tissue boundaries in 85% of cases. Results improve on state-of-the-art neonatal tissue segmentation models and significant errors were found in only 2% of cases, where these corresponded to subjects with high motion. Downstream, these surfaces will enhance comparisons of functional and diffusion MRI datasets, supporting the modelling of emerging patterns of brain connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Spatial resolution dependence on spectral frequency in human speech cortex electrocorticography

    Science.gov (United States)

    Muller, Leah; Hamilton, Liberty S.; Edwards, Erik; Bouchard, Kristofer E.; Chang, Edward F.

    2016-10-01

    Objective. Electrocorticography (ECoG) has become an important tool in human neuroscience and has tremendous potential for emerging applications in neural interface technology. Electrode array design parameters are outstanding issues for both research and clinical applications, and these parameters depend critically on the nature of the neural signals to be recorded. Here, we investigate the functional spatial resolution of neural signals recorded at the human cortical surface. We empirically derive spatial spread functions to quantify the shared neural activity for each frequency band of the electrocorticogram. Approach. Five subjects with high-density (4 mm center-to-center spacing) ECoG grid implants participated in speech perception and production tasks while neural activity was recorded from the speech cortex, including superior temporal gyrus, precentral gyrus, and postcentral gyrus. The cortical surface field potential was decomposed into traditional EEG frequency bands. Signal similarity between electrode pairs for each frequency band was quantified using a Pearson correlation coefficient. Main results. The correlation of neural activity between electrode pairs was inversely related to the distance between the electrodes; this relationship was used to quantify spatial falloff functions for cortical subdomains. As expected, lower frequencies remained correlated over larger distances than higher frequencies. However, both the envelope and phase of gamma and high gamma frequencies (30-150 Hz) are largely uncorrelated (<90%) at 4 mm, the smallest spacing of the high-density arrays. Thus, ECoG arrays smaller than 4 mm have significant promise for increasing signal resolution at high frequencies, whereas less additional gain is achieved for lower frequencies. Significance. Our findings quantitatively demonstrate the dependence of ECoG spatial resolution on the neural frequency of interest. We demonstrate that this relationship is consistent across patients and

  17. Neural Signatures of Trust During Human-Automation Interactions

    Science.gov (United States)

    2016-04-01

    also automated devices such as a Global Positioning System. For instance, to provide advanced safety measures, the Transportation Safety...AFRL-AFOSR-VA-TR-2016-0160 Neural Signatures of Trust during Human- Automation Interactions Frank Krueger GEORGE MASON UNIVERSITY Final Report 04/01...SUBTITLE Neural Signatures of Trust during Human- Automation Interactions 5a. CONTRACT NUMBER FA9550-13-1-0017 5b. GRANT NUMBER 5c. PROGRAM ELEMENT

  18. Cross-Linguistic Differences in the Neural Representation of Human Language: Evidence from Users of Signed Languages

    Science.gov (United States)

    Corina, David P.; Lawyer, Laurel A.; Cates, Deborah

    2013-01-01

    Studies of deaf individuals who are users of signed languages have provided profound insight into the neural representation of human language. Case studies of deaf signers who have incurred left- and right-hemisphere damage have shown that left-hemisphere resources are a necessary component of sign language processing. These data suggest that, despite frank differences in the input and output modality of language, core left perisylvian regions universally serve linguistic function. Neuroimaging studies of deaf signers have generally provided support for this claim. However, more fine-tuned studies of linguistic processing in deaf signers are beginning to show evidence of important differences in the representation of signed and spoken languages. In this paper, we provide a critical review of this literature and present compelling evidence for language-specific cortical representations in deaf signers. These data lend support to the claim that the neural representation of language may show substantive cross-linguistic differences. We discuss the theoretical implications of these findings with respect to an emerging understanding of the neurobiology of language. PMID:23293624

  19. Cortical connective field estimates from resting state fMRI activity

    NARCIS (Netherlands)

    Gravel, Nicolas; Harvey, Ben; Nordhjem, Barbara; Haak, Koen V.; Dumoulin, Serge O.; Renken, Remco; Curcic-Blake, Branisalava; Cornelissen, Frans W.

    2014-01-01

    One way to study connectivity in visual cortical areas is by examining spontaneous neural activity. In the absence of visual input, such activity remains shaped by the underlying neural architecture and, presumably, may still reflect visuotopic organization. Here, we applied population connective

  20. EEG-guided transcranial magnetic stimulation reveals rapid shifts in motor cortical excitability during the human sleep slow oscillation

    DEFF Research Database (Denmark)

    Bergmann, Til O; Mölle, Matthias; Schmidt, Marlit A

    2012-01-01

    Evoked cortical responses do not follow a rigid input–output function but are dynamically shaped by intrinsic neural properties at the time of stimulation. Recent research has emphasized the role of oscillatory activity in determining cortical excitability. Here we employed EEG-guided transcranial......, closely resembling a spontaneous SO. However, both MEPs and TEPs were consistently larger when evoked during SO up-states than during down-states, and ampliudes within each SO state depended on the actual EEG potential at the time and site of stimulation. These results provide first-time evidence...... magnetic stimulation (TMS) during non-rapid eye movement sleep to examine whether the spontaneous

  1. File list: His.Neu.05.AllAg.Cortical_neuron [Chip-atlas[Archive

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    Lifescience Database Archive (English)

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  5. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  6. Cortical Networks for Visual Self-Recognition

    Science.gov (United States)

    Sugiura, Motoaki

    This paper briefly reviews recent developments regarding the brain mechanisms of visual self-recognition. A special cognitive mechanism for visual self-recognition has been postulated based on behavioral and neuropsychological evidence, but its neural substrate remains controversial. Recent functional imaging studies suggest that multiple cortical mechanisms play self-specific roles during visual self-recognition, reconciling the existing controversy. Respective roles for the left occipitotemporal, right parietal, and frontal cortices in symbolic, visuospatial, and conceptual aspects of self-representation have been proposed.

  7. Cortical networks for visual self-recognition

    International Nuclear Information System (INIS)

    Sugiura, Motoaki

    2007-01-01

    This paper briefly reviews recent developments regarding the brain mechanisms of visual self-recognition. A special cognitive mechanism for visual self-recognition has been postulated based on behavioral and neuropsychological evidence, but its neural substrate remains controversial. Recent functional imaging studies suggest that multiple cortical mechanisms play self-specific roles during visual self-recognition, reconciling the existing controversy. Respective roles for the left occipitotemporal, right parietal, and frontal cortices in symbolic, visuospatial, and conceptual aspects of self-representation have been proposed. (author)

  8. Perceptual learning modifies the functional specializations of visual cortical areas.

    Science.gov (United States)

    Chen, Nihong; Cai, Peng; Zhou, Tiangang; Thompson, Benjamin; Fang, Fang

    2016-05-17

    Training can improve performance of perceptual tasks. This phenomenon, known as perceptual learning, is strongest for the trained task and stimulus, leading to a widely accepted assumption that the associated neuronal plasticity is restricted to brain circuits that mediate performance of the trained task. Nevertheless, learning does transfer to other tasks and stimuli, implying the presence of more widespread plasticity. Here, we trained human subjects to discriminate the direction of coherent motion stimuli. The behavioral learning effect substantially transferred to noisy motion stimuli. We used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms underlying the transfer of learning. The TMS experiment revealed dissociable, causal contributions of V3A (one of the visual areas in the extrastriate visual cortex) and MT+ (middle temporal/medial superior temporal cortex) to coherent and noisy motion processing. Surprisingly, the contribution of MT+ to noisy motion processing was replaced by V3A after perceptual training. The fMRI experiment complemented and corroborated the TMS finding. Multivariate pattern analysis showed that, before training, among visual cortical areas, coherent and noisy motion was decoded most accurately in V3A and MT+, respectively. After training, both kinds of motion were decoded most accurately in V3A. Our findings demonstrate that the effects of perceptual learning extend far beyond the retuning of specific neural populations for the trained stimuli. Learning could dramatically modify the inherent functional specializations of visual cortical areas and dynamically reweight their contributions to perceptual decisions based on their representational qualities. These neural changes might serve as the neural substrate for the transfer of perceptual learning.

  9. Brainlab: A Python Toolkit to Aid in the Design, Simulation, and Analysis of Spiking Neural Networks with the NeoCortical Simulator.

    Science.gov (United States)

    Drewes, Rich; Zou, Quan; Goodman, Philip H

    2009-01-01

    Neuroscience modeling experiments often involve multiple complex neural network and cell model variants, complex input stimuli and input protocols, followed by complex data analysis. Coordinating all this complexity becomes a central difficulty for the experimenter. The Python programming language, along with its extensive library packages, has emerged as a leading "glue" tool for managing all sorts of complex programmatic tasks. This paper describes a toolkit called Brainlab, written in Python, that leverages Python's strengths for the task of managing the general complexity of neuroscience modeling experiments. Brainlab was also designed to overcome the major difficulties of working with the NCS (NeoCortical Simulator) environment in particular. Brainlab is an integrated model-building, experimentation, and data analysis environment for the powerful parallel spiking neural network simulator system NCS.

  10. Cortical entrainment to music and its modulation by expertise.

    Science.gov (United States)

    Doelling, Keith B; Poeppel, David

    2015-11-10

    Recent studies establish that cortical oscillations track naturalistic speech in a remarkably faithful way. Here, we test whether such neural activity, particularly low-frequency (music and whether experience modifies such a cortical phenomenon. Music of varying tempi was used to test entrainment at different rates. In three magnetoencephalography experiments, we recorded from nonmusicians, as well as musicians with varying years of experience. Recordings from nonmusicians demonstrate cortical entrainment that tracks musical stimuli over a typical range of tempi, but not at tempi below 1 note per second. Importantly, the observed entrainment correlates with performance on a concurrent pitch-related behavioral task. In contrast, the data from musicians show that entrainment is enhanced by years of musical training, at all presented tempi. This suggests a bidirectional relationship between behavior and cortical entrainment, a phenomenon that has not previously been reported. Additional analyses focus on responses in the beta range (∼15-30 Hz)-often linked to delta activity in the context of temporal predictions. Our findings provide evidence that the role of beta in temporal predictions scales to the complex hierarchical rhythms in natural music and enhances processing of musical content. This study builds on important findings on brainstem plasticity and represents a compelling demonstration that cortical neural entrainment is tightly coupled to both musical training and task performance, further supporting a role for cortical oscillatory activity in music perception and cognition.

  11. Organizing Principles of Human Cortical Development--Thickness and Area from 4 to 30 Years: Insights from Comparative Primate Neuroanatomy.

    Science.gov (United States)

    Amlien, Inge K; Fjell, Anders M; Tamnes, Christian K; Grydeland, Håkon; Krogsrud, Stine K; Chaplin, Tristan A; Rosa, Marcello G P; Walhovd, Kristine B

    2016-01-01

    The human cerebral cortex undergoes a protracted, regionally heterogeneous development well into young adulthood. Cortical areas that expand the most during human development correspond to those that differ most markedly when the brains of macaque monkeys and humans are compared. However, it remains unclear to what extent this relationship derives from allometric scaling laws that apply to primate brains in general, or represents unique evolutionary adaptations. Furthermore, it is unknown whether the relationship only applies to surface area (SA), or also holds for cortical thickness (CT). In 331 participants aged 4 to 30, we calculated age functions of SA and CT, and examined the correspondence of human cortical development with macaque to human expansion, and with expansion across nonhuman primates. CT followed a linear negative age function from 4 to 30 years, while SA showed positive age functions until 12 years with little further development. Differential cortical expansion across primates was related to regional maturation of SA and CT, with age trajectories differing between high- and low-expanding cortical regions. This relationship adhered to allometric scaling laws rather than representing uniquely macaque-human differences: regional correspondence with human development was as large for expansion across nonhuman primates as between humans and macaque. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Use of functional near-infrared spectroscopy to monitor cortical plasticity induced by transcranial direct current stimulation

    Science.gov (United States)

    Khan, Bilal; Hervey, Nathan; Stowe, Ann; Hodics, Timea; Alexandrakis, George

    2013-03-01

    Electrical stimulation of the human cortex in conjunction with physical rehabilitation has been a valuable approach in facilitating the plasticity of the injured brain. One such method is transcranial direct current stimulation (tDCS) which is a non-invasive method to elicit neural stimulation by delivering current through electrodes placed on the scalp. In order to better understand the effects tDCS has on cortical plasticity, neuroimaging techniques have been used pre and post tDCS stimulation. Recently, neuroimaging methods have discovered changes in resting state cortical hemodynamics after the application of tDCS on human subjects. However, analysis of the cortical hemodynamic activity for a physical task during and post tDCS stimulation has not been studied to our knowledge. A viable and sensitive neuroimaging method to map changes in cortical hemodynamics during activation is functional near-infrared spectroscopy (fNIRS). In this study, the cortical activity during an event-related, left wrist curl task was mapped with fNIRS before, during, and after tDCS stimulation on eight healthy adults. Along with the fNIRS optodes, two electrodes were placed over the sensorimotor hand areas of both brain hemispheres to apply tDCS. Changes were found in both resting state cortical connectivity and cortical activation patterns that occurred during and after tDCS. Additionally, changes to surface electromyography (sEMG) measurements of the wrist flexor and extensor of both arms during the wrist curl movement, acquired concurrently with fNIRS, were analyzed and related to the transient cortical plastic changes induced by tDCS.

  13. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    Directory of Open Access Journals (Sweden)

    Hayato Fukusumi

    2016-01-01

    Full Text Available Human neural progenitor cells (hNPCs have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi. Our results showed that expandable hNPCs could be generated from hiPSC clones with diverse somatic tissue origins. The established hNPCs exhibited a mid/hindbrain-type neural identity and uniform expression of neural progenitor genes.

  14. Static human face recognition using artificial neural networks

    International Nuclear Information System (INIS)

    Qamar, R.; Shah, S.H.; Javed-ur-Rehman

    2003-01-01

    This paper presents a novel method of human face recognition using digital computers. A digital PC camera is used to take the BMP images of the human faces. An artificial neural network using Back Propagation Algorithm is developed as a recognition engine. The BMP images of the faces serve as the input patterns for this engine. A software 'Face Recognition' has been developed to recognize the human faces for which it is trained. Once the neural network is trained for patterns of the faces, the software is able to detect and recognize them with success rate of about 97%. (author)

  15. Deep Neural Networks Reveal a Gradient in the Complexity of Neural Representations across the Ventral Stream.

    Science.gov (United States)

    Güçlü, Umut; van Gerven, Marcel A J

    2015-07-08

    Converging evidence suggests that the primate ventral visual pathway encodes increasingly complex stimulus features in downstream areas. We quantitatively show that there indeed exists an explicit gradient for feature complexity in the ventral pathway of the human brain. This was achieved by mapping thousands of stimulus features of increasing complexity across the cortical sheet using a deep neural network. Our approach also revealed a fine-grained functional specialization of downstream areas of the ventral stream. Furthermore, it allowed decoding of representations from human brain activity at an unsurpassed degree of accuracy, confirming the quality of the developed approach. Stimulus features that successfully explained neural responses indicate that population receptive fields were explicitly tuned for object categorization. This provides strong support for the hypothesis that object categorization is a guiding principle in the functional organization of the primate ventral stream. Copyright © 2015 the authors 0270-6474/15/3510005-10$15.00/0.

  16. 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.

  17. Relating Cortical Wave Dynamics to Learning and Remembering

    Directory of Open Access Journals (Sweden)

    Eduardo Mercado III

    2014-12-01

    Full Text Available Electrical waves propagate across sensory and motor cortices in stereotypical patterns. These waves have been described as potentially facilitating sensory processing when they travel through sensory cortex, as guiding movement preparation and performance when they travel across motor cortex, and as possibly promoting synaptic plasticity and the consolidation of memory traces, especially during sleep. Here, an alternative theoretical framework is suggested that integrates Pavlovian hypotheses about learning and cortical function with concepts from contemporary proceduralist theories of memory. The proposed framework postulates that sensory-evoked cortical waves are gradually modified across repeated experiences such that the waves more effectively differentiate sensory events, and so that the waves are more likely to reverberate. It is argued that the qualities of cortical waves—their origins, form, intensity, speed, periodicity, extent, and trajectories —are a function of both the structural organization of neural circuits and ongoing reverberations resulting from previously experienced events. It is hypothesized that experience-dependent cortical plasticity, both in the short- and long-term, modulates the qualities of cortical waves, thereby enabling individuals to make progressively more precise distinctions between complex sensory events, and to reconstruct components of previously experienced events. Unlike most current neurobiological theories of learning and memory mechanisms, this hypothesis does not assume that synaptic plasticity, or any other form of neural plasticity, serves to store physical records of previously experienced events for later reactivation. Rather, the reorganization of cortical circuits may alter the potential for certain wave patterns to arise and persist. Understanding what factors determine the spatiotemporal dynamics of cortical waves, how structural changes affect their qualities, and how wave dynamics

  18. Neural representations and the cortical body matrix: implications for sports medicine and future directions.

    Science.gov (United States)

    Wallwork, Sarah B; Bellan, Valeria; Catley, Mark J; Moseley, G Lorimer

    2016-08-01

    Neural representations, or neurotags, refer to the idea that networks of brain cells, distributed across multiple brain areas, work in synergy to produce outputs. The brain can be considered then, a complex array of neurotags, each influencing and being influenced by each other. The output of some neurotags act on other systems, for example, movement, or on consciousness, for example, pain. This concept of neurotags has sparked a new body of research into pain and rehabilitation. We draw on this research and the concept of a cortical body matrix-a network of representations that subserves the regulation and protection of the body and the space around it-to suggest important implications for rehabilitation of sports injury and for sports performance. Protective behaviours associated with pain have been reinterpreted in light of these conceptual models. With a particular focus on rehabilitation of the injured athlete, this review presents the theoretical underpinnings of the cortical body matrix and its application within the sporting context. Therapeutic approaches based on these ideas are discussed and the efficacy of the most tested approaches is addressed. By integrating current thought in pain and cognitive neuroscience related to sports rehabilitation, recommendations for clinical practice and future research are suggested. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. Analysis of the volumetric relationship among human ocular, orbital and fronto-occipital cortical morphology

    Science.gov (United States)

    Masters, Michael; Bruner, Emiliano; Queer, Sarah; Traynor, Sarah; Senjem, Jess

    2015-01-01

    Recent research on the visual system has focused on investigating the relationship among eye (ocular), orbital, and visual cortical anatomy in humans. This issue is relevant in evolutionary and medical fields. In terms of evolution, only in modern humans and Neandertals are the orbits positioned beneath the frontal lobes, with consequent structural constraints. In terms of medicine, such constraints can be associated with minor deformation of the eye, vision defects, and patterns of integration among these features, and in association with the frontal lobes, are important to consider in reconstructive surgery. Further study is therefore necessary to establish how these variables are related, and to what extent ocular size is associated with orbital and cerebral cortical volumes. Relationships among these anatomical components were investigated using magnetic resonance images from a large sample of 83 individuals, which also included each subject’s body height, age, sex, and uncorrected visual acuity score. Occipital and frontal gyri volumes were calculated using two different cortical parcellation tools in order to provide a better understanding of how the eye and orbit vary in relation to visual cortical gyri, and frontal cortical gyri which are not directly related to visual processing. Results indicated that ocular and orbital volumes were weakly correlated, and that eye volume explains only a small proportion of the variance in orbital volume. Ocular and orbital volumes were also found to be equally and, in most cases, more highly correlated with five frontal lobe gyri than with occipital lobe gyri associated with V1, V2, and V3 of the visual cortex. Additionally, after accounting for age and sex variation, the relationship between ocular and total visual cortical volume was no longer statistically significant, but remained significantly related to total frontal lobe volume. The relationship between orbital and visual cortical volumes remained significant for

  20. Analysis of the volumetric relationship among human ocular, orbital and fronto-occipital cortical morphology.

    Science.gov (United States)

    Masters, Michael; Bruner, Emiliano; Queer, Sarah; Traynor, Sarah; Senjem, Jess

    2015-10-01

    Recent research on the visual system has focused on investigating the relationship among eye (ocular), orbital, and visual cortical anatomy in humans. This issue is relevant in evolutionary and medical fields. In terms of evolution, only in modern humans and Neandertals are the orbits positioned beneath the frontal lobes, with consequent structural constraints. In terms of medicine, such constraints can be associated with minor deformation of the eye, vision defects, and patterns of integration among these features, and in association with the frontal lobes, are important to consider in reconstructive surgery. Further study is therefore necessary to establish how these variables are related, and to what extent ocular size is associated with orbital and cerebral cortical volumes. Relationships among these anatomical components were investigated using magnetic resonance images from a large sample of 83 individuals, which also included each subject's body height, age, sex, and uncorrected visual acuity score. Occipital and frontal gyri volumes were calculated using two different cortical parcellation tools in order to provide a better understanding of how the eye and orbit vary in relation to visual cortical gyri, and frontal cortical gyri which are not directly related to visual processing. Results indicated that ocular and orbital volumes were weakly correlated, and that eye volume explains only a small proportion of the variance in orbital volume. Ocular and orbital volumes were also found to be equally and, in most cases, more highly correlated with five frontal lobe gyri than with occipital lobe gyri associated with V1, V2, and V3 of the visual cortex. Additionally, after accounting for age and sex variation, the relationship between ocular and total visual cortical volume was no longer statistically significant, but remained significantly related to total frontal lobe volume. The relationship between orbital and visual cortical volumes remained significant for a

  1. Cognitive-Neural Effects of Brush Writing of Chinese Characters: Cortical Excitation of Theta Rhythm

    Directory of Open Access Journals (Sweden)

    Min Xu

    2013-01-01

    Full Text Available Chinese calligraphy has been scientifically investigated within the contexts and principles of psychology, cognitive science, and the cognitive neuroscience. On the basis of vast amount of research in the last 30 years, we have developed a cybernetic theory of handwriting and calligraphy to account for the intricate interactions of several psychological dimensions involved in the dynamic act of graphic production. Central to this system of writing are the role of sensory, bio-, cognitive, and neurofeedback mechanisms for the initiation, guidance, and regulation of the writing motions vis-a-vis visual-geometric variations of Chinese characters. This experiment provided the first evidence of cortical excitation in EEG theta wave as a neural hub that integrates information coming from changes in the practitioner’s body, emotions, and cognition. In addition, it has also confirmed neurofeedback as an essential component of the cybernetic theory of handwriting and calligraphy.

  2. Development of Self-Assembled Nanoribbon Bound Peptide-Polyaniline Composite Scaffolds and Their Interactions with Neural Cortical Cells

    Directory of Open Access Journals (Sweden)

    Andrew M. Smith

    2018-01-01

    Full Text Available Degenerative neurological disorders and traumatic brain injuries cause significant damage to quality of life and often impact survival. As a result, novel treatments are necessary that can allow for the regeneration of neural tissue. In this work, a new biomimetic scaffold was designed with potential for applications in neural tissue regeneration. To develop the scaffold, we first prepared a new bolaamphiphile that was capable of undergoing self-assembly into nanoribbons at pH 7. Those nanoribbons were then utilized as templates for conjugation with specific proteins known to play a critical role in neural tissue growth. The template (Ile-TMG-Ile was prepared by conjugating tetramethyleneglutaric acid with isoleucine and the ability of the bolaamphiphile to self-assemble was probed at a pH range of 4 through 9. The nanoribbons formed under neutral conditions were then functionalized step-wise with the basement membrane protein laminin, the neurotropic factor artemin and Type IV collagen. The conductive polymer polyaniline (PANI was then incorporated through electrostatic and π–π stacking interactions to the scaffold to impart electrical properties. Distinct morphology changes were observed upon conjugation with each layer, which was also accompanied by an increase in Young’s Modulus as well as surface roughness. The Young’s Modulus of the dried PANI-bound biocomposite scaffolds was found to be 5.5 GPa, indicating the mechanical strength of the scaffold. Thermal phase changes studied indicated broad endothermic peaks upon incorporation of the proteins which were diminished upon binding with PANI. The scaffolds also exhibited in vitro biodegradable behavior over a period of three weeks. Furthermore, we observed cell proliferation and short neurite outgrowths in the presence of rat neural cortical cells, confirming that the scaffolds may be applicable in neural tissue regeneration. The electrochemical properties of the scaffolds were also

  3. Development of Self-Assembled Nanoribbon Bound Peptide-Polyaniline Composite Scaffolds and Their Interactions with Neural Cortical Cells

    Science.gov (United States)

    Smith, Andrew M.; Pajovich, Harrison T.; Banerjee, Ipsita A.

    2018-01-01

    Degenerative neurological disorders and traumatic brain injuries cause significant damage to quality of life and often impact survival. As a result, novel treatments are necessary that can allow for the regeneration of neural tissue. In this work, a new biomimetic scaffold was designed with potential for applications in neural tissue regeneration. To develop the scaffold, we first prepared a new bolaamphiphile that was capable of undergoing self-assembly into nanoribbons at pH 7. Those nanoribbons were then utilized as templates for conjugation with specific proteins known to play a critical role in neural tissue growth. The template (Ile-TMG-Ile) was prepared by conjugating tetramethyleneglutaric acid with isoleucine and the ability of the bolaamphiphile to self-assemble was probed at a pH range of 4 through 9. The nanoribbons formed under neutral conditions were then functionalized step-wise with the basement membrane protein laminin, the neurotropic factor artemin and Type IV collagen. The conductive polymer polyaniline (PANI) was then incorporated through electrostatic and π–π stacking interactions to the scaffold to impart electrical properties. Distinct morphology changes were observed upon conjugation with each layer, which was also accompanied by an increase in Young’s Modulus as well as surface roughness. The Young’s Modulus of the dried PANI-bound biocomposite scaffolds was found to be 5.5 GPa, indicating the mechanical strength of the scaffold. Thermal phase changes studied indicated broad endothermic peaks upon incorporation of the proteins which were diminished upon binding with PANI. The scaffolds also exhibited in vitro biodegradable behavior over a period of three weeks. Furthermore, we observed cell proliferation and short neurite outgrowths in the presence of rat neural cortical cells, confirming that the scaffolds may be applicable in neural tissue regeneration. The electrochemical properties of the scaffolds were also studied by

  4. Brainlab: a Python toolkit to aid in the design, simulation, and analysis of spiking neural networks with the NeoCortical Simulator

    Directory of Open Access Journals (Sweden)

    Richard P Drewes

    2009-05-01

    Full Text Available Neuroscience modeling experiments often involve multiple complex neural network and cell model variants, complex input stimuli and input protocols, followed by complex data analysis. Coordinating all this complexity becomes a central difficulty for the experimenter. The Python programming language, along with its extensive library packages, has emerged as a leading ``glue'' tool for managing all sorts of complex programmatictasks. This paper describes a toolkit called Brainlab, written in Python, that leverages Python's strengths for the task of managing the general complexity of neuroscience modeling experiments. Brainlab was also designed to overcome the major difficulties of working with the NCS environment in particular. Brainlab is an integrated model building, experimentation, and data analysis environment for the powerful parallel spiking neural network simulator system NCS (the NeoCortical Simulator.

  5. Cortical networks dynamically emerge with the interplay of slow and fast oscillations for memory of a natural scene.

    Science.gov (United States)

    Mizuhara, Hiroaki; Sato, Naoyuki; Yamaguchi, Yoko

    2015-05-01

    Neural oscillations are crucial for revealing dynamic cortical networks and for serving as a possible mechanism of inter-cortical communication, especially in association with mnemonic function. The interplay of the slow and fast oscillations might dynamically coordinate the mnemonic cortical circuits to rehearse stored items during working memory retention. We recorded simultaneous EEG-fMRI during a working memory task involving a natural scene to verify whether the cortical networks emerge with the neural oscillations for memory of the natural scene. The slow EEG power was enhanced in association with the better accuracy of working memory retention, and accompanied cortical activities in the mnemonic circuits for the natural scene. Fast oscillation showed a phase-amplitude coupling to the slow oscillation, and its power was tightly coupled with the cortical activities for representing the visual images of natural scenes. The mnemonic cortical circuit with the slow neural oscillations would rehearse the distributed natural scene representations with the fast oscillation for working memory retention. The coincidence of the natural scene representations could be obtained by the slow oscillation phase to create a coherent whole of the natural scene in the working memory. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Trade-off of cerebello-cortical and cortico-cortical functional networks for planning in 6-year-old children.

    Science.gov (United States)

    Kipping, Judy A; Margulies, Daniel S; Eickhoff, Simon B; Lee, Annie; Qiu, Anqi

    2018-05-03

    Childhood is a critical period for the development of cognitive planning. There is a lack of knowledge on its neural mechanisms in children. This study aimed to examine cerebello-cortical and cortico-cortical functional connectivity in association with planning skills in 6-year-olds (n = 76). We identified the cerebello-cortical and cortico-cortical functional networks related to cognitive planning using activation likelihood estimation (ALE) meta-analysis on existing functional imaging studies on spatial planning, and data-driven independent component analysis (ICA) of children's resting-state functional MRI (rs-fMRI). We investigated associations of cerebello-cortical and cortico-cortical functional connectivity with planning ability in 6-year-olds, as assessed using the Stockings of Cambridge task. Long-range functional connectivity of two cerebellar networks (lobules VI and lateral VIIa) with the prefrontal and premotor cortex were greater in children with poorer planning ability. In contrast, cortico-cortical association networks were not associated with the performance of planning in children. These results highlighted the key contribution of the lateral cerebello-frontal functional connectivity, but not cortico-cortical association functional connectivity, for planning ability in 6-year-olds. Our results suggested that brain adaptation to the acquisition of planning ability during childhood is partially achieved through the engagement of the cerebello-cortical functional connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Neural Priming in Human Frontal Cortex: Multiple Forms of Learning Reduce Demands on the Prefrontal Executive System

    Science.gov (United States)

    Race, Elizabeth A.; Shanker, Shanti; Wagner, Anthony D.

    2009-01-01

    Past experience is hypothesized to reduce computational demands in PFC by providing bottom-up predictive information that informs subsequent stimulus-action mapping. The present fMRI study measured cortical activity reductions ("neural priming"/"repetition suppression") during repeated stimulus classification to investigate the mechanisms through…

  8. 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

  9. Synapse-centric mapping of cortical models to the SpiNNaker neuromorphic architecture

    Directory of Open Access Journals (Sweden)

    James Courtney Knight

    2016-09-01

    Full Text Available While the adult human brain has approximately 8.8x10^10 neurons, this number is dwarfed by its 1x10^15 synapses. From the point of view of neuromorphic engineering and neural simulation in general this makes the simulation of these synapses a particularly complex problem. SpiNNaker is a digital, neuromorphic architecture designed for simulating large-scale spiking neural networks at speeds close to biological real-time. Current solutions for simulating spiking neural networks on SpiNNaker are heavily inspired by work on distributed high-performance computing. However, while SpiNNaker shares many characteristics with such distributed systems, its component nodes have much more limited resources and, as the system lacks global synchronization, the computation performed on each node must complete within a fixed time step. We first analyze the performance of the current SpiNNaker neural simulation software and identify several problems that occur when it is used to simulate networks of the type often used to model the cortex which contain large numbers of sparsely connected synapses. We then present a new, more flexible approach for mapping the simulation of such networks to SpiNNaker which solves many of these problems. Finally we analyze the performance of our new approach using both benchmarks, designed to represent cortical connectivity, and larger, functional cortical models. In a benchmark network where neurons receive input from 8000 STDP synapses, our new approach allows more neurons to be simulated on each SpiNNaker core than has been previously possible. We also demonstrate that the largest plastic neural network previously simulated on neuromorphic hardware can be run in real time using our new approach: double the speed that was previously achieved. Additionally this network contains two types of plastic synapse which previously had to be trained separately but, using our new approach, can be trained simultaneously.

  10. Similar patterns of neural activity predict memory function during encoding and retrieval.

    Science.gov (United States)

    Kragel, James E; Ezzyat, Youssef; Sperling, Michael R; Gorniak, Richard; Worrell, Gregory A; Berry, Brent M; Inman, Cory; Lin, Jui-Jui; Davis, Kathryn A; Das, Sandhitsu R; Stein, Joel M; Jobst, Barbara C; Zaghloul, Kareem A; Sheth, Sameer A; Rizzuto, Daniel S; Kahana, Michael J

    2017-07-15

    Neural networks that span the medial temporal lobe (MTL), prefrontal cortex, and posterior cortical regions are essential to episodic memory function in humans. Encoding and retrieval are supported by the engagement of both distinct neural pathways across the cortex and common structures within the medial temporal lobes. However, the degree to which memory performance can be determined by neural processing that is common to encoding and retrieval remains to be determined. To identify neural signatures of successful memory function, we administered a delayed free-recall task to 187 neurosurgical patients implanted with subdural or intraparenchymal depth electrodes. We developed multivariate classifiers to identify patterns of spectral power across the brain that independently predicted successful episodic encoding and retrieval. During encoding and retrieval, patterns of increased high frequency activity in prefrontal, MTL, and inferior parietal cortices, accompanied by widespread decreases in low frequency power across the brain predicted successful memory function. Using a cross-decoding approach, we demonstrate the ability to predict memory function across distinct phases of the free-recall task. Furthermore, we demonstrate that classifiers that combine information from both encoding and retrieval states can outperform task-independent models. These findings suggest that the engagement of a core memory network during either encoding or retrieval shapes the ability to remember the past, despite distinct neural interactions that facilitate encoding and retrieval. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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.

  12. Plasticity of cortical excitatory-inhibitory balance.

    Science.gov (United States)

    Froemke, Robert C

    2015-07-08

    Synapses are highly plastic and are modified by changes in patterns of neural activity or sensory experience. Plasticity of cortical excitatory synapses is thought to be important for learning and memory, leading to alterations in sensory representations and cognitive maps. However, these changes must be coordinated across other synapses within local circuits to preserve neural coding schemes and the organization of excitatory and inhibitory inputs, i.e., excitatory-inhibitory balance. Recent studies indicate that inhibitory synapses are also plastic and are controlled directly by a large number of neuromodulators, particularly during episodes of learning. Many modulators transiently alter excitatory-inhibitory balance by decreasing inhibition, and thus disinhibition has emerged as a major mechanism by which neuromodulation might enable long-term synaptic modifications naturally. This review examines the relationships between neuromodulation and synaptic plasticity, focusing on the induction of long-term changes that collectively enhance cortical excitatory-inhibitory balance for improving perception and behavior.

  13. Automatic segmentation of human cortical layer-complexes and architectural areas using diffusion MRI and its validation

    Directory of Open Access Journals (Sweden)

    Matteo Bastiani

    2016-11-01

    Full Text Available Recently, several magnetic resonance imaging contrast mechanisms have been shown to distinguish cortical substructure corresponding to selected cortical layers. Here, we investigate cortical layer and area differentiation by automatized unsupervised clustering of high resolution diffusion MRI data. Several groups of adjacent layers could be distinguished in human primary motor and premotor cortex. We then used the signature of diffusion MRI signals along cortical depth as a criterion to detect area boundaries and find borders at which the signature changes abruptly. We validate our clustering results by histological analysis of the same tissue. These results confirm earlier studies which show that diffusion MRI can probe layer-specific intracortical fiber organization and, moreover, suggests that it contains enough information to automatically classify architecturally distinct cortical areas. We discuss the strengths and weaknesses of the automatic clustering approach and its appeal for MR-based cortical histology.

  14. Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition.

    Science.gov (United States)

    Bast, Tobias; Pezze, Marie; McGarrity, Stephanie

    2017-10-01

    We review recent evidence concerning the significance of inhibitory GABA transmission and of neural disinhibition, that is, deficient GABA transmission, within the prefrontal cortex and the hippocampus, for clinically relevant cognitive functions. Both regions support important cognitive functions, including attention and memory, and their dysfunction has been implicated in cognitive deficits characterizing neuropsychiatric disorders. GABAergic inhibition shapes cortico-hippocampal neural activity, and, recently, prefrontal and hippocampal neural disinhibition has emerged as a pathophysiological feature of major neuropsychiatric disorders, especially schizophrenia and age-related cognitive decline. Regional neural disinhibition, disrupting spatio-temporal control of neural activity and causing aberrant drive of projections, may disrupt processing within the disinhibited region and efferent regions. Recent studies in rats showed that prefrontal and hippocampal neural disinhibition (by local GABA antagonist microinfusion) dysregulates burst firing, which has been associated with important aspects of neural information processing. Using translational tests of clinically relevant cognitive functions, these studies showed that prefrontal and hippocampal neural disinhibition disrupts regional cognitive functions (including prefrontal attention and hippocampal memory function). Moreover, hippocampal neural disinhibition disrupted attentional performance, which does not require the hippocampus but requires prefrontal-striatal circuits modulated by the hippocampus. However, some prefrontal and hippocampal functions (including inhibitory response control) are spared by regional disinhibition. We consider conceptual implications of these findings, regarding the distinct relationships of distinct cognitive functions to prefrontal and hippocampal GABA tone and neural activity. Moreover, the findings support the proposition that prefrontal and hippocampal neural disinhibition

  15. Isolation and characterization of neural stem cells from human fetal striatum

    International Nuclear Information System (INIS)

    Li Xiaoxia; Xu Jinchong; Bai Yun; Wang Xuan; Dai Xin; Liu Yinan; Zhang Jun; Zou Junhua; Shen Li; Li Lingsong

    2005-01-01

    This paper described that neural stem cells (hsNSCs) were isolated and expanded rapidly from human fetal striatum in adherent culture. The population was serum- and growth factor-dependent and expressed neural stem cell markers. They were capable of multi-differentiation into neurons, astrocytes, and oligodendrocytes. When plated in the dopaminergic neuron inducing medium, human striatum neural stem cells could differentiate into tyrosine hydroxylase positive neurons. hsNSCs were morphologically homogeneous and possessed high proliferation ability. The population doubled every 44.28 h and until now it has divided for more than 82 generations in vitro. Normal human diploid karyotype was unchanged throughout the in vitro culture period. Together, this study has exploited a method for continuous and rapid expansion of human neural stem cells as pure population, which maintained the capacity to generate almost fifty percent neurons. The availability of such cells may hold great interest for basic and applied neuroscience

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

    Science.gov (United States)

    Secundo, Lavi

    , the correlation of ECoG activity to kinematic parameters of arm movement is context-dependent, an important constraint to consider in future development of BMI systems. The third chapter delves into a fundamental organizational principle of the primate motor system---cortical control of contralateral limb movements. However, ipsilateral motor areas also appear to play a role in the control of ipsilateral limb movements. Several studies in monkeys have shown that individual neurons in ipsilateral primary motor cortex (M1) may represent, on average, the direction of movements of the ipsilateral arm. Given the increasing body of evidence demonstrating that neural ensembles can reliably represent information with a high temporal resolution, here we characterize the distributed neural representation of ipsilateral upper limb kinematics in both monkey and man. In two macaque monkeys trained to perform center-out reaching movements, we found that the ensemble spiking activity in M1 could continuously represent ipsilateral limb position. We also recorded cortical field potentials from three human subjects and also consistently found evidence of a neural representation for ipsilateral movement parameters. Together, our results demonstrate the presence of a high-fidelity neural representation for ipsilateral movement and illustrates that it can be successfully incorporated into a brain-machine interface.

  17. Cortical inactivation by cooling in small animals

    Directory of Open Access Journals (Sweden)

    Ben eCoomber

    2011-06-01

    Full Text Available Reversible inactivation of the cortex by surface cooling is a powerful method for studying the function of a particular area. Implanted cooling cryoloops have been used to study the role of individual cortical areas in auditory processing of awake-behaving cats. Cryoloops have also been used in rodents for reversible inactivation of the cortex, but recently there has been a concern that the cryoloop may also cool non-cortical structures either directly or via the perfusion of blood, cooled as it passed close to the cooling loop. In this study we have confirmed that the loop can inactivate most of the auditory cortex without causing a significant reduction in temperature of the auditory thalamus or other sub-cortical structures. We placed a cryoloop on the surface of the guinea pig cortex, cooled it to 2°C and measured thermal gradients across the neocortical surface. We found that the temperature dropped to 20-24°C among cells within a radius of about 2.5mm away from the loop. This temperature drop was sufficient to reduce activity of most cortical cells and led to the inactivation of almost the entire auditory region. When the temperature of thalamus, midbrain, and middle ear were measured directly during cortical cooling, there was a small drop in temperature (about 4°C but this was not sufficient to directly reduce neural activity. In an effort to visualise the extent of neural inactivation we measured the uptake of thallium ions following an intravenous injection. This confirmed that there was a large reduction of activity across much of the ipsilateral cortex and only a small reduction in subcortical structures.

  18. Neuroimaging in human MDMA (Ecstasy) users: A cortical model

    Science.gov (United States)

    Cowan, Ronald L; Roberts, Deanne M; Joers, James M

    2009-01-01

    MDMA (3,4 methylenedioxymethamphetamine) has been used by millions of people worldwide as a recreational drug. MDMA and Ecstasy are often used synonymously but it is important to note that the purity of Ecstasy sold as MDMA is not certain. MDMA use is of public health concern, not so much because MDMA produces a common or severe dependence syndrome, but rather because rodent and non-human primate studies have indicated that MDMA (when administered at certain dosages and intervals) can cause long-lasting reductions in markers of brain serotonin (5-HT) that appear specific to fine diameter axons arising largely from the dorsal raphe nucleus (DR). Given the popularity of MDMA, the potential for the drug to produce long-lasting or permanent 5-HT axon damage or loss, and the widespread role of 5-HT function in the brain, there is a great need for a better understanding of brain function in human users of this drug. To this end, neuropsychological, neuroendocrine, and neuroimaging studies have all suggested that human MDMA users may have long-lasting changes in brain function consistent with 5-HT toxicity. Data from animal models leads to testable hypotheses regarding MDMA effects on the human brain. Because neuropsychological and neuroimaging findings have focused on the neocortex, a cortical model is developed to provide context for designing and interpreting neuroimaging studies in MDMA users. Aspects of the model are supported by the available neuroimaging data but there are controversial findings in some areas and most findings have not been replicated across different laboratories and using different modalities. This paper reviews existing findings in the context of a cortical model and suggests directions for future research. PMID:18991874

  19. Higher cortical modulation of pain perception in the human brain: Psychological determinant

    OpenAIRE

    Chen, Andrew Cn

    2009-01-01

    Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed d...

  20. Hypothesis-driven methods to augment human cognition by optimizing cortical oscillations

    Directory of Open Access Journals (Sweden)

    Jörn M. Horschig

    2014-06-01

    Full Text Available Cortical oscillations have been shown to represent fundamental functions of a working brain, e.g. communication, stimulus binding, error monitoring, and inhibition, and are directly linked to behavior. Recent studies intervening with these oscillations have demonstrated effective modulation of both the oscillations and behavior. In this review, we collect evidence in favor of how hypothesis-driven methods can be used to augment cognition by optimizing cortical oscillations. We elaborate their potential usefulness for three target groups: healthy elderly, patients with attention deficit/hyperactivity disorder, and healthy young adults. We discuss the relevance of neuronal oscillations in each group and show how each of them can benefit from the manipulation of functionally-related oscillations. Further, we describe methods for manipulation of neuronal oscillations including direct brain stimulation as well as indirect task alterations. We also discuss practical considerations about the proposed techniques. In conclusion, we propose that insights from neuroscience should guide techniques to augment human cognition, which in turn can provide a better understanding of how the human brain works.

  1. Cortical control of gait in healthy humans: an fMRI study

    International Nuclear Information System (INIS)

    ChiHong, Wang; YauYau, Wai; BoCheng, Kuo; Yei-Yu, Yeh; JiunJie Wang

    2008-01-01

    This study examined the cortical control of gait in healthy humans using functional magnetic resonance imaging (fMRI). Two block-designed fMRI sessions were conducted during motor imagery of a locomotor-related task. Subjects watched a video clip that showed an actor standing and walking in an egocentric perspective. In a control session, additional fMRI images were collected when participants observed a video clip of the clutch movement of a right hand. In keeping with previous studies using SPECT and NIRS, we detected activation in many motor-related areas including supplementary motor area, bilateral precentral gyrus, left dorsal premotor cortex, and cingulate motor area. Smaller additional activations were observed in the bilateral precuneus, left thalamus, and part of right putamen. Based on these findings, we propose a novel paradigm to study the cortical control of gait in healthy humans using fMRI. Specifically, the task used in this study - involving both mirror neurons and mental imagery - provides a new feasible model to be used in functional neuroimaging studies in this area of research. (author)

  2. Culture-sensitive neural substrates of human cognition: a transcultural neuroimaging approach.

    Science.gov (United States)

    Han, Shihui; Northoff, Georg

    2008-08-01

    Our brains and minds are shaped by our experiences, which mainly occur in the context of the culture in which we develop and live. Although psychologists have provided abundant evidence for diversity of human cognition and behaviour across cultures, the question of whether the neural correlates of human cognition are also culture-dependent is often not considered by neuroscientists. However, recent transcultural neuroimaging studies have demonstrated that one's cultural background can influence the neural activity that underlies both high- and low-level cognitive functions. The findings provide a novel approach by which to distinguish culture-sensitive from culture-invariant neural mechanisms of human cognition.

  3. Cortical interneurons from human pluripotent stem cells: prospects for neurological and psychiatric disease

    Directory of Open Access Journals (Sweden)

    Charles Edward Arber

    2013-03-01

    Full Text Available Cortical interneurons represent 20% of the cells in the cortex. These cells are local inhibitory neurons whose function is to modulate the firing activities of the excitatory projection neurons. Cortical interneuron dysfunction is believed to lead to runaway excitation underlying (or implicated in seizure-based diseases, such as epilepsy, autism and schizophrenia. The complex development of this cell type and the intricacies involved in defining the relative subtypes are being increasingly well defined. This has led to exciting experimental cell therapy in model organisms, whereby fetal-derived interneuron precursors can reverse seizure severity and reduce mortality in adult epileptic rodents. These proof-of-principle studies raise hope for potential interneuron-based transplantation therapies for treating epilepsy. On the other hand, cortical neurons generated from patient iPSCs serve as a valuable tool to explore genetic influences of interneuron development and function. This is a fundamental step in enhancing our understanding of the molecular basis of neuropsychiatric illnesses and the development of targeted treatments. Protocols are currently being developed for inducing cortical interneuron subtypes from mouse and human pluripotent stem cells. This review sets out to summarize the progress made in cortical interneuron development, fetal tissue transplantation and the recent advance in stem cell differentiation towards interneurons.

  4. Non-Viral Generation of Neural Precursor-like Cells from Adult Human Fibroblasts

    Directory of Open Access Journals (Sweden)

    Maucksch C

    2012-01-01

    Full Text Available Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP-expressing astrocytes. This study represents a novel virus-free approach for direct reprogramming of human fibroblasts to a neural precursor fate.

  5. Cortical Thought Theory: A Working Model of the Human Gestalt Mechanism.

    Science.gov (United States)

    1985-07-01

    2. The Artificial Inteligence Perspective • -° 2.1 Introduction: Chapter Overview This chapter addresses the development of a...6 . . 2. The Artificial Intelligence Perspective ... .......... 9 2.1 Introduction: Chapter Overview .... ........... 9 2.2 The Problem 9...new unified theory of human brain function called Cortical Thought Theory (CTT). The analysis integrates the disciplines of Artificial Intelligence

  6. The hominoid-specific gene TBC1D3 promotes generation of basal neural progenitors and induces cortical folding in mice

    Science.gov (United States)

    Ju, Xiang-Chun; Hou, Qiong-Qiong; Sheng, Ai-Li; Wu, Kong-Yan; Zhou, Yang; Jin, Ying; Wen, Tieqiao; Yang, Zhengang; Wang, Xiaoqun; Luo, Zhen-Ge

    2016-01-01

    Cortical expansion and folding are often linked to the evolution of higher intelligence, but molecular and cellular mechanisms underlying cortical folding remain poorly understood. The hominoid-specific gene TBC1D3 undergoes segmental duplications during hominoid evolution, but its role in brain development has not been explored. Here, we found that expression of TBC1D3 in ventricular cortical progenitors of mice via in utero electroporation caused delamination of ventricular radial glia cells (vRGs) and promoted generation of self-renewing basal progenitors with typical morphology of outer radial glia (oRG), which are most abundant in primates. Furthermore, down-regulation of TBC1D3 in cultured human brain slices decreased generation of oRGs. Interestingly, localized oRG proliferation resulting from either in utero electroporation or transgenic expression of TBC1D3, was often found to underlie cortical regions exhibiting folding. Thus, we have identified a hominoid gene that is required for oRG generation in regulating the cortical expansion and folding. DOI: http://dx.doi.org/10.7554/eLife.18197.001 PMID:27504805

  7. Optimal staining methods for delineation of cortical areas and neuron counts in human brains.

    Science.gov (United States)

    Uylings, H B; Zilles, K; Rajkowska, G

    1999-04-01

    For cytoarchitectonic delineation of cortical areas in human brain, the Gallyas staining for somata with its sharp contrast between cell bodies and neuropil is preferable to the classical Nissl staining, the more so when an image analysis system is used. This Gallyas staining, however, does not appear to be appropriate for counting neuron numbers in pertinent brain areas, due to the lack of distinct cytological features between small neurons and glial cells. For cell counting Nissl is preferable. In an optimal design for cell counting at least both the Gallyas and the Nissl staining must be applied, the former staining for cytoarchitectural delineaton of cortical areas and the latter for counting the number of neurons in the pertinent cortical areas. Copyright 1999 Academic Press.

  8. Cortical thickness in adolescent marijuana and alcohol users: A three-year prospective study from adolescence to young adulthood.

    Science.gov (United States)

    Jacobus, Joanna; Squeglia, Lindsay M; Meruelo, Alejandro D; Castro, Norma; Brumback, Ty; Giedd, Jay N; Tapert, Susan F

    2015-12-01

    Studies suggest marijuana impacts gray and white matter neural tissue development, however few prospective studies have determined the relationship between cortical thickness and cannabis use spanning adolescence to young adulthood. This study aimed to understand how heavy marijuana use influences cortical thickness trajectories across adolescence. Subjects were adolescents with heavy marijuana use and concomitant alcohol use (MJ+ALC, n=30) and controls (CON, n=38) with limited substance use histories. Participants underwent magnetic resonance imaging and comprehensive substance use assessment at three independent time points. Repeated measures analysis of covariance was used to look at main effects of group, time, and Group × Time interactions on cortical thickness. MJ+ALC showed thicker cortical estimates across the brain (23 regions), particularly in frontal and parietal lobes (psadolescence and into young adulthood may be associated with altered neural tissue development and interference with neuromaturation that can have neurobehavioral consequences. Continued follow-up of adolescent marijuana users will help understand ongoing neural changes that are associated with development of problematic use into adulthood, as well as potential for neural recovery with cessation of use. Published by Elsevier Ltd.

  9. Evidence for a cerebral cortical thickness network anti-correlated with amygdalar volume in healthy youths: implications for the neural substrates of emotion regulation.

    Science.gov (United States)

    Albaugh, Matthew D; Ducharme, Simon; Collins, D Louis; Botteron, Kelly N; Althoff, Robert R; Evans, Alan C; Karama, Sherif; Hudziak, James J

    2013-05-01

    Recent functional connectivity studies have demonstrated that, in resting humans, activity in a dorsally-situated neocortical network is inversely associated with activity in the amygdalae. Similarly, in human neuroimaging studies, aspects of emotion regulation have been associated with increased activity in dorsolateral, dorsomedial, orbital and ventromedial prefrontal regions, as well as concomitant decreases in amygdalar activity. These findings indicate the presence of two countervailing systems in the human brain that are reciprocally related: a dorsally-situated cognitive control network, and a ventrally-situated limbic network. We investigated the extent to which this functional reciprocity between limbic and dorsal neocortical regions is recapitulated from a purely structural standpoint. Specifically, we hypothesized that amygdalar volume would be related to cerebral cortical thickness in cortical regions implicated in aspects of emotion regulation. In 297 typically developing youths (162 females, 135 males; 572 MRIs), the relationship between cortical thickness and amygdalar volume was characterized. Amygdalar volume was found to be inversely associated with thickness in bilateral dorsolateral and dorsomedial prefrontal, inferior parietal, as well as bilateral orbital and ventromedial prefrontal cortices. Our findings are in line with previous work demonstrating that a predominantly dorsally-centered neocortical network is reciprocally related to core limbic structures such as the amygdalae. Future research may benefit from investigating the extent to which such cortical-limbic morphometric relations are qualified by the presence of mood and anxiety psychopathology. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Background noise exerts diverse effects on the cortical encoding of foreground sounds.

    Science.gov (United States)

    Malone, B J; Heiser, Marc A; Beitel, Ralph E; Schreiner, Christoph E

    2017-08-01

    In natural listening conditions, many sounds must be detected and identified in the context of competing sound sources, which function as background noise. Traditionally, noise is thought to degrade the cortical representation of sounds by suppressing responses and increasing response variability. However, recent studies of neural network models and brain slices have shown that background synaptic noise can improve the detection of signals. Because acoustic noise affects the synaptic background activity of cortical networks, it may improve the cortical responses to signals. We used spike train decoding techniques to determine the functional effects of a continuous white noise background on the responses of clusters of neurons in auditory cortex to foreground signals, specifically frequency-modulated sweeps (FMs) of different velocities, directions, and amplitudes. Whereas the addition of noise progressively suppressed the FM responses of some cortical sites in the core fields with decreasing signal-to-noise ratios (SNRs), the stimulus representation remained robust or was even significantly enhanced at specific SNRs in many others. Even though the background noise level was typically not explicitly encoded in cortical responses, significant information about noise context could be decoded from cortical responses on the basis of how the neural representation of the foreground sweeps was affected. These findings demonstrate significant diversity in signal in noise processing even within the core auditory fields that could support noise-robust hearing across a wide range of listening conditions. NEW & NOTEWORTHY The ability to detect and discriminate sounds in background noise is critical for our ability to communicate. The neural basis of robust perceptual performance in noise is not well understood. We identified neuronal populations in core auditory cortex of squirrel monkeys that differ in how they process foreground signals in background noise and that may

  11. Groupwise connectivity-based parcellation of the whole human cortical surface using watershed-driven dimension reduction.

    Science.gov (United States)

    Lefranc, Sandrine; Roca, Pauline; Perrot, Matthieu; Poupon, Cyril; Le Bihan, Denis; Mangin, Jean-François; Rivière, Denis

    2016-05-01

    Segregating the human cortex into distinct areas based on structural connectivity criteria is of widespread interest in neuroscience. This paper presents a groupwise connectivity-based parcellation framework for the whole cortical surface using a new high quality diffusion dataset of 79 healthy subjects. Our approach performs gyrus by gyrus to parcellate the whole human cortex. The main originality of the method is to compress for each gyrus the connectivity profiles used for the clustering without any anatomical prior information. This step takes into account the interindividual cortical and connectivity variability. To this end, we consider intersubject high density connectivity areas extracted using a surface-based watershed algorithm. A wide validation study has led to a fully automatic pipeline which is robust to variations in data preprocessing (tracking type, cortical mesh characteristics and boundaries of initial gyri), data characteristics (including number of subjects), and the main algorithmic parameters. A remarkable reproducibility is achieved in parcellation results for the whole cortex, leading to clear and stable cortical patterns. This reproducibility has been tested across non-overlapping subgroups and the validation is presented mainly on the pre- and postcentral gyri. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network

    Science.gov (United States)

    Weick, Jason P.; Liu, Yan; Zhang, Su-Chun

    2011-01-01

    Whether hESC-derived neurons can fully integrate with and functionally regulate an existing neural network remains unknown. Here, we demonstrate that hESC-derived neurons receive unitary postsynaptic currents both in vitro and in vivo and adopt the rhythmic firing behavior of mouse cortical networks via synaptic integration. Optical stimulation of hESC-derived neurons expressing Channelrhodopsin-2 elicited both inhibitory and excitatory postsynaptic currents and triggered network bursting in mouse neurons. Furthermore, light stimulation of hESC-derived neurons transplanted to the hippocampus of adult mice triggered postsynaptic currents in host pyramidal neurons in acute slice preparations. Thus, hESC-derived neurons can participate in and modulate neural network activity through functional synaptic integration, suggesting they are capable of contributing to neural network information processing both in vitro and in vivo. PMID:22106298

  13. Neural correlate of human reciprocity in social interactions.

    Science.gov (United States)

    Sakaiya, Shiro; Shiraito, Yuki; Kato, Junko; Ide, Hiroko; Okada, Kensuke; Takano, Kouji; Kansaku, Kenji

    2013-01-01

    Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human) and strategy (random, tit-for-tat) in repeated prisoner's dilemma games and investigated the neural correlate of reciprocal interaction with humans. Reciprocal cooperation with humans but exploitation of computers by defection was associated with activation in the left amygdala. Amygdala activation was also positively and negatively correlated with a preference change for human partners following tit-for-tat and random strategies, respectively. The correlated activation represented the intensity of positive feeling toward reciprocal and negative feeling toward non-reciprocal partners, and so reflected reciprocity in social interaction. Reciprocity in social interaction, however, might plausibly be misinterpreted and so we also examined the neural coding of insight into the reciprocity of partners. Those with and without insight revealed differential brain activation across the reward-related circuitry (i.e., the right middle dorsolateral prefrontal cortex and dorsal caudate) and theory of mind (ToM) regions [i.e., ventromedial prefrontal cortex (VMPFC) and precuneus]. Among differential activations, activation in the precuneus, which accompanied deactivation of the VMPFC, was specific to those without insight into human partners who were engaged in a tit-for-tat strategy. This asymmetric (de)activation might involve specific contributions of ToM regions to the human search for reciprocity. Consequently, the intensity of emotion attached to human reciprocity was represented in the amygdala, whereas insight into the reciprocity of others was reflected in activation across the reward-related and ToM regions. This suggests the critical role of mentalizing, which was not equated with reward expectation during social interactions.

  14. Neural correlate of human reciprocity in social interactions

    Directory of Open Access Journals (Sweden)

    Shiro eSakaiya

    2013-12-01

    Full Text Available Reciprocity plays a key role maintaining cooperation in society. However, little is known about the neural process that underpins human reciprocity during social interactions. Our neuroimaging study manipulated partner identity (computer, human and strategy (random, tit-for-tat in repeated prisoner’s dilemma games and investigated the neural correlate of reciprocal interaction with humans. Reciprocal cooperation with humans but exploitation of computers by defection was associated with activation in the left amygdala. Amygdala activation was also positively and negatively correlated with a preference change for human partners following tit-for-tat and random strategies, respectively. The correlated activation represented the intensity of positive feeling toward reciprocal and negative feeling toward non-reciprocal partners, and so reflected reciprocity in social interaction. Reciprocity in social interaction, however, might plausibly be misinterpreted and so we also examined the neural coding of insight into the reciprocity of partners. Those with and without insight revealed differential brain activation across the reward-related circuitry (i.e., the right middle dorsolateral prefrontal cortex and dorsal caudate and theory of mind (ToM regions (i.e., ventromedial prefrontal cortex [VMPFC] and precuneus. Among differential activations, activation in the precuneus, which accompanied deactivation of the VMPFC, was specific to those without insight into human partners who were engaged in a tit-for-tat strategy. This asymmetric (deactivation might involve specific contributions of ToM regions to the human search for reciprocity. Consequently, the intensity of emotion attached to human reciprocity was represented in the amygdala, whereas insight into the reciprocity of others was reflected in activation across the reward-related and ToM regions. This suggests the critical role of mentalizing, which was not equated with reward expectation during

  15. Cortical topography of intracortical inhibition influences the speed of decision making.

    Science.gov (United States)

    Wilimzig, Claudia; Ragert, Patrick; Dinse, Hubert R

    2012-02-21

    The neocortex contains orderly topographic maps; however, their functional role remains controversial. Theoretical studies have suggested a role in minimizing computational costs, whereas empirical studies have focused on spatial localization. Using a tactile multiple-choice reaction time (RT) task before and after the induction of perceptual learning through repetitive sensory stimulation, we extend the framework of cortical topographies by demonstrating that the topographic arrangement of intracortical inhibition contributes to the speed of human perceptual decision-making processes. RTs differ among fingers, displaying an inverted U-shaped function. Simulations using neural fields show the inverted U-shaped RT distribution as an emergent consequence of lateral inhibition. Weakening inhibition through learning shortens RTs, which is modeled through topographically reorganized inhibition. Whereas changes in decision making are often regarded as an outcome of higher cortical areas, our data show that the spatial layout of interaction processes within representational maps contributes to selection and decision-making processes.

  16. 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.

  17. Establishment of Human Neural Progenitor Cells from Human Induced Pluripotent Stem Cells with Diverse Tissue Origins

    OpenAIRE

    Hayato Fukusumi; Tomoko Shofuda; Yohei Bamba; Atsuyo Yamamoto; Daisuke Kanematsu; Yukako Handa; Keisuke Okita; Masaya Nakamura; Shinya Yamanaka; Hideyuki Okano; Yonehiro Kanemura

    2016-01-01

    Human neural progenitor cells (hNPCs) have previously been generated from limited numbers of human induced pluripotent stem cell (hiPSC) clones. Here, 21 hiPSC clones derived from human dermal fibroblasts, cord blood cells, and peripheral blood mononuclear cells were differentiated using two neural induction methods, an embryoid body (EB) formation-based method and an EB formation method using dual SMAD inhibitors (dSMADi). Our results showed that expandable hNPCs could be generated from hiPS...

  18. 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.

  19. Deep recurrent neural network reveals a hierarchy of process memory during dynamic natural vision.

    Science.gov (United States)

    Shi, Junxing; Wen, Haiguang; Zhang, Yizhen; Han, Kuan; Liu, Zhongming

    2018-05-01

    The human visual cortex extracts both spatial and temporal visual features to support perception and guide behavior. Deep convolutional neural networks (CNNs) provide a computational framework to model cortical representation and organization for spatial visual processing, but unable to explain how the brain processes temporal information. To overcome this limitation, we extended a CNN by adding recurrent connections to different layers of the CNN to allow spatial representations to be remembered and accumulated over time. The extended model, or the recurrent neural network (RNN), embodied a hierarchical and distributed model of process memory as an integral part of visual processing. Unlike the CNN, the RNN learned spatiotemporal features from videos to enable action recognition. The RNN better predicted cortical responses to natural movie stimuli than the CNN, at all visual areas, especially those along the dorsal stream. As a fully observable model of visual processing, the RNN also revealed a cortical hierarchy of temporal receptive window, dynamics of process memory, and spatiotemporal representations. These results support the hypothesis of process memory, and demonstrate the potential of using the RNN for in-depth computational understanding of dynamic natural vision. © 2018 Wiley Periodicals, Inc.

  20. Modulation of financial deprivation on deception and its neural correlates.

    Science.gov (United States)

    Sun, Peng; Ling, Xiaoli; Zheng, Li; Chen, Jia; Li, Lin; Liu, Zhiyuan; Cheng, Xuemei; Guo, Xiuyan

    2017-11-01

    Deception is a universal phenomenon in human society and plays an important role in everyday life. Previous studies have revealed that people might have an internalized moral norm of keeping honest and the deceptive behavior was reliably correlated with activation in executive brain regions of prefrontal cortices to over-ride intuitive honest responses. Using functional magnetic resonance imaging, this study sought to investigate how financial position modulated the neural responses during deceptive decision. Twenty-one participants were scanned when they played a series of adapted Dictator Game with different partners after a ball-guess game. Specifically, participants gained or lost money in the ball-guess game, and had opportunities to get more financial gains through cheating in the following adapted Dictator Game. Behavioral results indicated that participants did not cheat to the full extent; instead they were more likely to lie after losing money compared with gaining money. At the neural level, weaker activities in the dorsolateral prefrontal cortices were observed when participants lied after losing money than gaining money. Together, our data indicated that, people really had an internalized norm of keeping honest, but it would be lenient when people feel financial deprivation. And suppressing the truthful response originating from moral norm of keeping honest was associated with increased level of activation in the dorsolateral prefrontal cortices, but this association became weaker when people were under financial deprivation.

  1. REMODELING SENSORY CORTICAL MAPS IMPLANTS SPECIFIC BEHAVIORAL MEMORY

    Science.gov (United States)

    Bieszczad, Kasia M.; Miasnikov, Alexandre A.; Weinberger, Norman M.

    2013-01-01

    Neural mechanisms underlying the capacity of memory to be rich with sensory detail are largely unknown. A candidate mechanism is learning-induced plasticity that remodels adult sensory cortex. Here, expansion in the primary auditory cortical (A1) tonotopic map of rats was induced by pairing a 3.66 kHz tone with activation of the nucleus basalis, mimicking the effects of natural associative learning. Remodeling of A1 produced de novo specific behavioral memory, but neither memory nor plasticity were consistently at the frequency of the paired tone, which typically decreased in A1 representation. Rather, there was a specific match between individual subjects’ area of expansion and the tone that was strongest in each animal’s memory, as determined by post-training frequency generalization gradients. These findings provide the first demonstration of a match between the artificial induction of specific neural representational plasticity and artificial induction of behavioral memory. As such, together with prior and present findings for detection, correlation and mimicry of plasticity with the acquisition of memory, they satisfy a key criterion for neural substrates of memory. This demonstrates that directly remodeling sensory cortical maps is sufficient for the specificity of memory formation. PMID:23639876

  2. Neural growth into a microchannel network: towards a regenerative neural interface

    NARCIS (Netherlands)

    Wieringa, P.A.; Wiertz, Remy; le Feber, Jakob; Rutten, Wim

    2009-01-01

    We propose and validated a design for a highly selective 'endcap' regenerative neural interface towards a neuroprosthesis. In vitro studies using rat cortical neurons determine if a branching microchannel structure can counter fasciculated growth and cause neurites to separte from one another,

  3. Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.

    Science.gov (United States)

    Berkes, Pietro; Orbán, Gergo; Lengyel, Máté; Fiser, József

    2011-01-07

    The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.

  4. A Subtype of Inhibitory Interneuron with Intrinsic Persistent Activity in Human and Monkey Neocortex

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2015-03-01

    Full Text Available A critical step in understanding the neural basis of human cognitive functions is to identify neuronal types in the neocortex. In this study, we performed whole-cell recording from human cortical slices and found a distinct subpopulation of neurons with intrinsic persistent activity that could be triggered by single action potentials (APs but terminated by bursts of APs. This persistent activity was associated with a depolarizing plateau potential induced by the activation of a persistent Na+ current. Single-cell RT-PCR revealed that these neurons were inhibitory interneurons. This type of neuron was found in different cortical regions, including temporal, frontal, occipital, and parietal cortices in human and also in frontal and temporal lobes of nonhuman primate but not in rat cortical tissues, suggesting that it could be unique to primates. The characteristic persistent activity in these inhibitory interneurons may contribute to the regulation of pyramidal cell activity and participate in cortical processing.

  5. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans.

    Science.gov (United States)

    Nitsche, M A; Fricke, K; Henschke, U; Schlitterlau, A; Liebetanz, D; Lang, N; Henning, S; Tergau, F; Paulus, W

    2003-11-15

    Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested. tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.

  6. 101 labeled brain images and a consistent human cortical labeling protocol

    Directory of Open Access Journals (Sweden)

    Arno eKlein

    2012-12-01

    Full Text Available We introduce the Mindboggle-101 dataset, the largest and most complete set of free, publicly accessible, manually labeled human brain images. To manually label the macroscopic anatomy in magnetic resonance images of 101 healthy participants, we created a new cortical labeling protocol that relies on robust anatomical landmarks and minimal manual edits after initialization with automated labels. The Desikan-Killiany-Tourville (DKT protocol is intended to improve the ease, consistency, and accuracy of labeling human cortical areas. Given how difficult it is to label brains, the Mindboggle-101 dataset is intended to serve as brain atlases for use in labeling other brains, as a normative dataset to establish morphometric variation in a healthy population for comparison against clinical populations, and contribute to the development, training, testing, and evaluation of automated registration and labeling algorithms. To this end, we also introduce benchmarks for the evaluation of such algorithms by comparing our manual labels with labels automatically generated by probabilistic and multi-atlas registration-based approaches. All data and related software and updated information are available on the http://www.mindboggle.info/data/ website.

  7. 101 Labeled Brain Images and a Consistent Human Cortical Labeling Protocol

    Science.gov (United States)

    Klein, Arno; Tourville, Jason

    2012-01-01

    We introduce the Mindboggle-101 dataset, the largest and most complete set of free, publicly accessible, manually labeled human brain images. To manually label the macroscopic anatomy in magnetic resonance images of 101 healthy participants, we created a new cortical labeling protocol that relies on robust anatomical landmarks and minimal manual edits after initialization with automated labels. The “Desikan–Killiany–Tourville” (DKT) protocol is intended to improve the ease, consistency, and accuracy of labeling human cortical areas. Given how difficult it is to label brains, the Mindboggle-101 dataset is intended to serve as brain atlases for use in labeling other brains, as a normative dataset to establish morphometric variation in a healthy population for comparison against clinical populations, and contribute to the development, training, testing, and evaluation of automated registration and labeling algorithms. To this end, we also introduce benchmarks for the evaluation of such algorithms by comparing our manual labels with labels automatically generated by probabilistic and multi-atlas registration-based approaches. All data and related software and updated information are available on the http://mindboggle.info/data website. PMID:23227001

  8. 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...

  9. Decoding Visual Location From Neural Patterns in the Auditory Cortex of the Congenitally Deaf

    Science.gov (United States)

    Almeida, Jorge; He, Dongjun; Chen, Quanjing; Mahon, Bradford Z.; Zhang, Fan; Gonçalves, Óscar F.; Fang, Fang; Bi, Yanchao

    2016-01-01

    Sensory cortices of individuals who are congenitally deprived of a sense can exhibit considerable plasticity and be recruited to process information from the senses that remain intact. Here, we explored whether the auditory cortex of congenitally deaf individuals represents visual field location of a stimulus—a dimension that is represented in early visual areas. We used functional MRI to measure neural activity in auditory and visual cortices of congenitally deaf and hearing humans while they observed stimuli typically used for mapping visual field preferences in visual cortex. We found that the location of a visual stimulus can be successfully decoded from the patterns of neural activity in auditory cortex of congenitally deaf but not hearing individuals. This is particularly true for locations within the horizontal plane and within peripheral vision. These data show that the representations stored within neuroplastically changed auditory cortex can align with dimensions that are typically represented in visual cortex. PMID:26423461

  10. The Neural Basis of Vocal Pitch Imitation in Humans.

    Science.gov (United States)

    Belyk, Michel; Pfordresher, Peter Q; Liotti, Mario; Brown, Steven

    2016-04-01

    Vocal imitation is a phenotype that is unique to humans among all primate species, and so an understanding of its neural basis is critical in explaining the emergence of both speech and song in human evolution. Two principal neural models of vocal imitation have emerged from a consideration of nonhuman animals. One hypothesis suggests that putative mirror neurons in the inferior frontal gyrus pars opercularis of Broca's area may be important for imitation. An alternative hypothesis derived from the study of songbirds suggests that the corticostriate motor pathway performs sensorimotor processes that are specific to vocal imitation. Using fMRI with a sparse event-related sampling design, we investigated the neural basis of vocal imitation in humans by comparing imitative vocal production of pitch sequences with both nonimitative vocal production and pitch discrimination. The strongest difference between these tasks was found in the putamen bilaterally, providing a striking parallel to the role of the analogous region in songbirds. Other areas preferentially activated during imitation included the orofacial motor cortex, Rolandic operculum, and SMA, which together outline the corticostriate motor loop. No differences were seen in the inferior frontal gyrus. The corticostriate system thus appears to be the central pathway for vocal imitation in humans, as predicted from an analogy with songbirds.

  11. Communication and Wiring in the Cortical Connectome

    Directory of Open Access Journals (Sweden)

    Julian eBudd

    2012-10-01

    Full Text Available In cerebral cortex, the huge mass of axonal wiring that carries information between near and distant neurons is thought to provide the neural substrate for cognitive and perceptual function. The goal of mapping the connectivity of cortical axons at different spatial scales, the cortical connectome, is to trace the paths of information flow in cerebral cortex. To appreciate the relationship between the connectome and cortical function, we need to discover the nature and purpose of the wiring principles underlying cortical connectivity. A popular explanation has been that axonal length is strictly minimized both within and between cortical regions. In contrast, we have hypothesized the existence of a multi-scale principle of cortical wiring where to optimise communication there is a trade-off between spatial (construction and temporal (routing costs. Here, using recent evidence concerning cortical spatial networks we critically evaluate this hypothesis at neuron, local circuit, and pathway scales. We report three main conclusions. First, the axonal and dendritic arbor morphology of single neocortical neurons may be governed by a similar wiring principle, one that balances the conservation of cellular material and conduction delay. Second, the same principle may be observed for fibre tracts connecting cortical regions. Third, the absence of sufficient local circuit data currently prohibits any meaningful assessment of the hypothesis at this scale of cortical organization. To avoid neglecting neuron and microcircuit levels of cortical organization, the connectome framework should incorporate more morphological description. In addition, structural analyses of temporal cost for cortical circuits should take account of both axonal conduction and neuronal integration delays, which appear mostly of the same order of magnitude. We conclude the hypothesized trade-off between spatial and temporal costs may potentially offer a powerful explanation for

  12. Biophysical Model of Cortical Network Activity and the Influence of Electrical Stimulation

    Science.gov (United States)

    2015-11-13

    model, multicompartment model, subdural cortical stimulation, anode, cathode, epilepsy REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S REPORT NUMBER(S...and axon orientation in respect to the electrode position. 4) A single stimulation pulse causes a sequence of action potentials ectopically generated...Bergey, P.J. Franaszczuk. Phase-dependent stimulation effects on bursting activity in a neural network cortical simulation, Epilepsy Research (07 2008

  13. Consciousness, plasticity, and connectomics: the role of intersubjectivity in human cognition

    DEFF Research Database (Denmark)

    Allen, Micah Galen; Williams, Gary

    2011-01-01

    motivates philosophical and empirical hypotheses regarding the appropriate time-scale and function of neuroplastic adaptation, the relation of high and low-frequency neural activity to consciousness and cognitive plasticity, and the role of ritual social practices in neural development and cognitive...... take up our account of consciousness from the observation of radical cortical neuroplasticity in human development. Accordingly, we draw upon recent research on macroscopic neural networks, including the “default mode,” to illustrate cases in which an individual’s particular “connectome” is shaped...

  14. Structural Analysis of Three-dimensional Human Neural Tissue derived from Induced Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Terrence Brooks, Patrick; Rasmussen, Mikkel Aabech; Hyttel, Poul

    2016-01-01

    Objective: The present study aimed at establishing a method for production of a three-dimensional (3D) human neural tissue derived from induced pluripotent stem cells (iPSCs) and analyzing the outcome by a combination of tissue ultrastructure and expression of neural markers. Methods: A two......-step cell culture procedure was implemented by subjecting human iPSCs to a 3D scaffoldbased neural differentiation protocol. First, neural fate-inducing small molecules were used to create a neuroepithelial monolayer. Second, the monolayer was trypsinized into single cells and seeded into a porous...... polystyrene scaffold and further cultured to produce a 3D neural tissue. The neural tissue was characterized by a combination of immunohistochemistry and transmission electron microscopy (TEM). Results: iPSCs developed into a 3D neural tissue expressing markers for neural progenitor cells, early neural...

  15. The relationship between level of processing and hippocampal-cortical functional connectivity during episodic memory formation in humans.

    Science.gov (United States)

    Schott, Björn H; Wüstenberg, Torsten; Wimber, Maria; Fenker, Daniela B; Zierhut, Kathrin C; Seidenbecher, Constanze I; Heinze, Hans-Jochen; Walter, Henrik; Düzel, Emrah; Richardson-Klavehn, Alan

    2013-02-01

    New episodic memory traces represent a record of the ongoing neocortical processing engaged during memory formation (encoding). Thus, during encoding, deep (semantic) processing typically establishes more distinctive and retrievable memory traces than does shallow (perceptual) processing, as assessed by later episodic memory tests. By contrast, the hippocampus appears to play a processing-independent role in encoding, because hippocampal lesions impair encoding regardless of level of processing. Here, we clarified the neural relationship between processing and encoding by examining hippocampal-cortical connectivity during deep and shallow encoding. Participants studied words during functional magnetic resonance imaging and freely recalled these words after distraction. Deep study processing led to better recall than shallow study processing. For both levels of processing, successful encoding elicited activations of bilateral hippocampus and left prefrontal cortex, and increased functional connectivity between left hippocampus and bilateral medial prefrontal, cingulate and extrastriate cortices. Successful encoding during deep processing was additionally associated with increased functional connectivity between left hippocampus and bilateral ventrolateral prefrontal cortex and right temporoparietal junction. In the shallow encoding condition, on the other hand, pronounced functional connectivity increases were observed between the right hippocampus and the frontoparietal attention network activated during shallow study processing. Our results further specify how the hippocampus coordinates recording of ongoing neocortical activity into long-term memory, and begin to provide a neural explanation for the typical advantage of deep over shallow study processing for later episodic memory. Copyright © 2011 Wiley Periodicals, Inc.

  16. Manipulation of Auditory Inputs as Rehabilitation Therapy for Maladaptive Auditory Cortical Reorganization

    Directory of Open Access Journals (Sweden)

    Hidehiko Okamoto

    2018-01-01

    Full Text Available Neurophysiological and neuroimaging data suggest that the brains of not only children but also adults are reorganized based on sensory inputs and behaviors. Plastic changes in the brain are generally beneficial; however, maladaptive cortical reorganization in the auditory cortex may lead to hearing disorders such as tinnitus and hyperacusis. Recent studies attempted to noninvasively visualize pathological neural activity in the living human brain and reverse maladaptive cortical reorganization by the suitable manipulation of auditory inputs in order to alleviate detrimental auditory symptoms. The effects of the manipulation of auditory inputs on maladaptively reorganized brain were reviewed herein. The findings obtained indicate that rehabilitation therapy based on the manipulation of auditory inputs is an effective and safe approach for hearing disorders. The appropriate manipulation of sensory inputs guided by the visualization of pathological brain activities using recent neuroimaging techniques may contribute to the establishment of new clinical applications for affected individuals.

  17. Cortical networks for encoding near and far space in the non-human primate.

    Science.gov (United States)

    Cléry, Justine; Guipponi, Olivier; Odouard, Soline; Wardak, Claire; Ben Hamed, Suliann

    2018-04-19

    While extra-personal space is often erroneously considered as a unique entity, early neuropsychological studies report a dissociation between near and far space processing both in humans and in monkeys. Here, we use functional MRI in a naturalistic 3D environment to describe the non-human primate near and far space cortical networks. We describe the co-occurrence of two extended functional networks respectively dedicated to near and far space processing. Specifically, far space processing involves occipital, temporal, parietal, posterior cingulate as well as orbitofrontal regions not activated by near space, possibly subserving the processing of the shape and identity of objects. In contrast, near space processing involves temporal, parietal, prefrontal and premotor regions not activated by far space, possibly subserving the preparation of an arm/hand mediated action in this proximal space. Interestingly, this network also involves somatosensory regions, suggesting a cross-modal anticipation of touch by a nearby object. Last, we also describe cortical regions that process both far and near space with a preference for one or the other. This suggests a continuous encoding of relative distance to the body, in the form of a far-to-near gradient. We propose that these cortical gradients in space representation subserve the physically delineable peripersonal spaces described in numerous psychology and psychophysics studies. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Automatic Detection of Cortical Bones Haversian Osteonal Boundaries

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    Ilige Hage

    2015-10-01

    Full Text Available This work aims to automatically detect cement lines in decalcified cortical bone sections stained with H&E. Employed is a methodology developed previously by the authors and proven to successfully count and disambiguate the micro-architectural features (namely Haversian canals, canaliculi, and osteocyte lacunae present in the secondary osteons/Haversian system (osteon of cortical bone. This methodology combines methods typically considered separately, namely pulse coupled neural networks (PCNN, particle swarm optimization (PSO, and adaptive threshold (AT. In lieu of human bone, slides (at 20× magnification from bovid cortical bone are used in this study as proxy of human bone. Having been characterized, features with same orientation are used to detect the cement line viewed as the next coaxial layer adjacent to the outermost lamella of the osteon. Employed for this purpose are three attributes for each and every micro-sized feature identified in the osteon lamellar system: (1 orientation, (2 size (ellipse perimeter and (3 Euler number (a topological measure. From a training image, automated parameters for the PCNN network are obtained by forming fitness functions extracted from these attributes. It is found that a 3-way combination of these features attributes yields good representations of the overall osteon boundary (cement line. Near-unity values of classical metrics of quality (precision, sensitivity, specificity, accuracy, and dice suggest that the segments obtained automatically by the optimized artificial intelligent methodology are of high fidelity as compared with manual tracing. For bench marking, cement lines segmented by k-means did not fare as well. An analysis based on the modified Hausdorff distance (MHD of the segmented cement lines also testified to the quality of the detected cement lines vis-a-vis the k-means method.

  19. Influence of mesh density, cortical thickness and material properties on human rib fracture prediction.

    Science.gov (United States)

    Li, Zuoping; Kindig, Matthew W; Subit, Damien; Kent, Richard W

    2010-11-01

    The purpose of this paper was to investigate the sensitivity of the structural responses and bone fractures of the ribs to mesh density, cortical thickness, and material properties so as to provide guidelines for the development of finite element (FE) thorax models used in impact biomechanics. Subject-specific FE models of the second, fourth, sixth and tenth ribs were developed to reproduce dynamic failure experiments. Sensitivity studies were then conducted to quantify the effects of variations in mesh density, cortical thickness, and material parameters on the model-predicted reaction force-displacement relationship, cortical strains, and bone fracture locations for all four ribs. Overall, it was demonstrated that rib FE models consisting of 2000-3000 trabecular hexahedral elements (weighted element length 2-3mm) and associated quadrilateral cortical shell elements with variable thickness more closely predicted the rib structural responses and bone fracture force-failure displacement relationships observed in the experiments (except the fracture locations), compared to models with constant cortical thickness. Further increases in mesh density increased computational cost but did not markedly improve model predictions. A ±30% change in the major material parameters of cortical bone lead to a -16.7 to 33.3% change in fracture displacement and -22.5 to +19.1% change in the fracture force. The results in this study suggest that human rib structural responses can be modeled in an accurate and computationally efficient way using (a) a coarse mesh of 2000-3000 solid elements, (b) cortical shells elements with variable thickness distribution and (c) a rate-dependent elastic-plastic material model. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

  20. Neural coding in graphs of bidirectional associative memories.

    Science.gov (United States)

    Bouchain, A David; Palm, Günther

    2012-01-24

    In the last years we have developed large neural network models for the realization of complex cognitive tasks in a neural network architecture that resembles the network of the cerebral cortex. We have used networks of several cortical modules that contain two populations of neurons (one excitatory, one inhibitory). The excitatory populations in these so-called "cortical networks" are organized as a graph of Bidirectional Associative Memories (BAMs), where edges of the graph correspond to BAMs connecting two neural modules and nodes of the graph correspond to excitatory populations with associative feedback connections (and inhibitory interneurons). The neural code in each of these modules consists essentially of the firing pattern of the excitatory population, where mainly it is the subset of active neurons that codes the contents to be represented. The overall activity can be used to distinguish different properties of the patterns that are represented which we need to distinguish and control when performing complex tasks like language understanding with these cortical networks. The most important pattern properties or situations are: exactly fitting or matching input, incomplete information or partially matching pattern, superposition of several patterns, conflicting information, and new information that is to be learned. We show simple simulations of these situations in one area or module and discuss how to distinguish these situations based on the overall internal activation of the module. This article is part of a Special Issue entitled "Neural Coding". Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Temporary interference over the posterior parietal cortices disrupts thermoregulatory control in humans.

    Directory of Open Access Journals (Sweden)

    Alberto Gallace

    Full Text Available The suggestion has recently been made that certain higher-order cortical areas involved in supporting multisensory representations of the body, and of the space around it, might also play a role in controlling thermoregulatory functions. Here we demonstrate that temporary interference with the function of one of these areas, the posterior parietal cortex, by repetitive transcranial magnetic stimulation, results in a decrease in limb temperature. By contrast, interference with the activity of a sensory-specific area (the primary somatosensory cortex had no effect on temperature. The results of this experiment suggest that associative multisensory brain areas might exert a top-down modulation over basic physiological control. Such a function might be part of a larger neural circuit responsible for maintaining the integrity of the body at both a homeostatic and a psychological level.

  2. Human-Specific Cortical Synaptic Connections and Their Plasticity: Is That What Makes Us Human?

    Directory of Open Access Journals (Sweden)

    Joana Lourenço

    2017-01-01

    Full Text Available One outstanding difference between Homo sapiens and other mammals is the ability to perform highly complex cognitive tasks and behaviors, such as language, abstract thinking, and cultural diversity. How is this accomplished? According to one prominent theory, cognitive complexity is proportional to the repetition of specific computational modules over a large surface expansion of the cerebral cortex (neocortex. However, the human neocortex was shown to also possess unique features at the cellular and synaptic levels, raising the possibility that expanding the computational module is not the only mechanism underlying complex thinking. In a study published in PLOS Biology, Szegedi and colleagues analyzed a specific cortical circuit from live postoperative human tissue, showing that human-specific, very powerful excitatory connections between principal pyramidal neurons and inhibitory neurons are highly plastic. This suggests that exclusive plasticity of specific microcircuits might be considered among the mechanisms endowing the human neocortex with the ability to perform highly complex cognitive tasks.

  3. Human cerebral cortices: signal variation on diffusion-weighted MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Asao, Chiaki [Kumamoto Regional Medical Center, Department of Radiology, Kumamoto (Japan); National Hospital Organization Kumamoto Medical Center, Department of Radiology, Kumamoto (Japan); Hirai, Toshinori; Yamashita, Yasuyuki [Kumamoto University Graduate School of Medical Sciences, Department of Diagnostic Radiology, Kumamoto (Japan); Yoshimatsu, Shunji [National Hospital Organization Kumamoto Medical Center, Department of Radiology, Kumamoto (Japan); Matsukawa, Tetsuya; Imuta, Masanori [Kumamoto Regional Medical Center, Department of Radiology, Kumamoto (Japan); Sagara, Katsuro [Kumamoto Regional Medical Center, Department of Internal Medicine, Kumamoto (Japan)

    2008-03-15

    We have often encountered high signal intensity (SI) of the cingulate gyrus and insula during diffusion-weighted magnetic resonance imaging (DW-MRI) on neurologically healthy adults. To date, cortical signal heterogeneity on DW images has not been investigated systematically. The purpose of our study was to determine whether there is regional signal variation in the brain cortices of neurologically healthy adults on DW-MR images. The SI of the cerebral cortices on DW-MR images at 1.5 T was evaluated in 50 neurologically healthy subjects (34 men, 16 women; age range 33-84 years; mean age 57.6 years). The cortical SI in the cingulate gyrus, insula, and temporal, occipital, and parietal lobes was graded relative to the SI of the frontal lobe. Contrast-to-noise ratios (CNRs) on DW-MR images were compared for each cortical area. Diffusion changes were analyzed by visually assessment of the differences in appearance among the cortices on apparent diffusion coefficient (ADC) maps. Increased SI was frequently seen in the cingulate gyrus and insula regardless of patient age. There were no significant gender- or laterality-related differences. The CNR was significantly higher in the cingulate gyrus and insula than in the other cortices (p <.01), and significant differences existed among the cortical regions (p <.001). There were no apparent ADC differences among the cortices on ADC maps. Regional signal variation of the brain cortices was observed on DW-MR images of healthy subjects, and the cingulate gyrus and insula frequently manifested high SI. These findings may help in the recognition of cortical signal abnormalities as visualized on DW-MR images. (orig.)

  4. Human cerebral cortices: signal variation on diffusion-weighted MR imaging

    International Nuclear Information System (INIS)

    Asao, Chiaki; Hirai, Toshinori; Yamashita, Yasuyuki; Yoshimatsu, Shunji; Matsukawa, Tetsuya; Imuta, Masanori; Sagara, Katsuro

    2008-01-01

    We have often encountered high signal intensity (SI) of the cingulate gyrus and insula during diffusion-weighted magnetic resonance imaging (DW-MRI) on neurologically healthy adults. To date, cortical signal heterogeneity on DW images has not been investigated systematically. The purpose of our study was to determine whether there is regional signal variation in the brain cortices of neurologically healthy adults on DW-MR images. The SI of the cerebral cortices on DW-MR images at 1.5 T was evaluated in 50 neurologically healthy subjects (34 men, 16 women; age range 33-84 years; mean age 57.6 years). The cortical SI in the cingulate gyrus, insula, and temporal, occipital, and parietal lobes was graded relative to the SI of the frontal lobe. Contrast-to-noise ratios (CNRs) on DW-MR images were compared for each cortical area. Diffusion changes were analyzed by visually assessment of the differences in appearance among the cortices on apparent diffusion coefficient (ADC) maps. Increased SI was frequently seen in the cingulate gyrus and insula regardless of patient age. There were no significant gender- or laterality-related differences. The CNR was significantly higher in the cingulate gyrus and insula than in the other cortices (p <.01), and significant differences existed among the cortical regions (p <.001). There were no apparent ADC differences among the cortices on ADC maps. Regional signal variation of the brain cortices was observed on DW-MR images of healthy subjects, and the cingulate gyrus and insula frequently manifested high SI. These findings may help in the recognition of cortical signal abnormalities as visualized on DW-MR images. (orig.)

  5. Neural correlates for perception of companion animal photographs.

    Science.gov (United States)

    Hayama, Sara; Chang, Linda; Gumus, Kazim; King, George R; Ernst, Thomas

    2016-05-01

    Anthrozoological neuroscience, which we propose as the use of neuroscience techniques to study human-animal interaction, may help to elucidate mechanisms underlying the associated psychological, physiological, and other purported health effects. This preliminary study investigates the neural response to animal photographs in pet owners and non-pet owners, and both attraction and attachment to companion animals as modulators of human perception of companion animal photographs. Thirty male participants, 15 "Pet Owners" (PO) and 15 "Non-Pet Owners" (NPO), viewed photographs of companion animals during functional MRI (fMRI) scans at 3 T and provided ratings of attraction to the animal species represented in the photographs. Fourteen subjects additionally submitted and viewed personal pet photographs during fMRI scans, and completed the Lexington Attachment to Pets Scale (LAPS). PO exhibited greater activation than NPO during the viewing of animal photographs in areas of the insula, and frontal and occipital cortices. Moreover, ratings of attraction to animals correlated positively with neural activation in the cingulate gyrus, precentral gyrus, inferior parietal lobule, and superior temporal gyrus during the viewing of representative photographs. For subjects with household pets, scores on the LAPS correlated positively with neural activation during the viewing of owned pet photographs in the precuneus, cuneus, and superior parietal lobule. Our preliminary findings suggest that human perception of companion animals involve the visual attention network, which may be modulated at the neural level by subjective experiences of attraction or attachment to animals. Our understanding of human-animal interactions through anthrozoological neuroscience may better direct therapeutic applications, such as animal-assisted therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. A Model of Representational Spaces in Human Cortex.

    Science.gov (United States)

    Guntupalli, J Swaroop; Hanke, Michael; Halchenko, Yaroslav O; Connolly, Andrew C; Ramadge, Peter J; Haxby, James V

    2016-06-01

    Current models of the functional architecture of human cortex emphasize areas that capture coarse-scale features of cortical topography but provide no account for population responses that encode information in fine-scale patterns of activity. Here, we present a linear model of shared representational spaces in human cortex that captures fine-scale distinctions among population responses with response-tuning basis functions that are common across brains and models cortical patterns of neural responses with individual-specific topographic basis functions. We derive a common model space for the whole cortex using a new algorithm, searchlight hyperalignment, and complex, dynamic stimuli that provide a broad sampling of visual, auditory, and social percepts. The model aligns representations across brains in occipital, temporal, parietal, and prefrontal cortices, as shown by between-subject multivariate pattern classification and intersubject correlation of representational geometry, indicating that structural principles for shared neural representations apply across widely divergent domains of information. The model provides a rigorous account for individual variability of well-known coarse-scale topographies, such as retinotopy and category selectivity, and goes further to account for fine-scale patterns that are multiplexed with coarse-scale topographies and carry finer distinctions. © The Author 2016. Published by Oxford University Press.

  7. Extensive cochleotopic mapping of human auditory cortical fields obtained with phase-encoding FMRI.

    Directory of Open Access Journals (Sweden)

    Ella Striem-Amit

    Full Text Available The primary sensory cortices are characterized by a topographical mapping of basic sensory features which is considered to deteriorate in higher-order areas in favor of complex sensory features. Recently, however, retinotopic maps were also discovered in the higher-order visual, parietal and prefrontal cortices. The discovery of these maps enabled the distinction between visual regions, clarified their function and hierarchical processing. Could such extension of topographical mapping to high-order processing regions apply to the auditory modality as well? This question has been studied previously in animal models but only sporadically in humans, whose anatomical and functional organization may differ from that of animals (e.g. unique verbal functions and Heschl's gyrus curvature. Here we applied fMRI spectral analysis to investigate the cochleotopic organization of the human cerebral cortex. We found multiple mirror-symmetric novel cochleotopic maps covering most of the core and high-order human auditory cortex, including regions considered non-cochleotopic, stretching all the way to the superior temporal sulcus. These maps suggest that topographical mapping persists well beyond the auditory core and belt, and that the mirror-symmetry of topographical preferences may be a fundamental principle across sensory modalities.

  8. The neural sociometer: brain mechanisms underlying state self-esteem.

    Science.gov (United States)

    Eisenberger, Naomi I; Inagaki, Tristen K; Muscatell, Keely A; Byrne Haltom, Kate E; Leary, Mark R

    2011-11-01

    On the basis of the importance of social connection for survival, humans may have evolved a "sociometer"-a mechanism that translates perceptions of rejection or acceptance into state self-esteem. Here, we explored the neural underpinnings of the sociometer by examining whether neural regions responsive to rejection or acceptance were associated with state self-esteem. Participants underwent fMRI while viewing feedback words ("interesting," "boring") ostensibly chosen by another individual (confederate) to describe the participant's previously recorded interview. Participants rated their state self-esteem in response to each feedback word. Results demonstrated that greater activity in rejection-related neural regions (dorsal ACC, anterior insula) and mentalizing regions was associated with lower-state self-esteem. Additionally, participants whose self-esteem decreased from prescan to postscan versus those whose self-esteem did not showed greater medial prefrontal cortical activity, previously associated with self-referential processing, in response to negative feedback. Together, the results inform our understanding of the origin and nature of our feelings about ourselves.

  9. Developing a hippocampal neural prosthetic to facilitate human memory encoding and recall

    Science.gov (United States)

    Hampson, Robert E.; Song, Dong; Robinson, Brian S.; Fetterhoff, Dustin; Dakos, Alexander S.; Roeder, Brent M.; She, Xiwei; Wicks, Robert T.; Witcher, Mark R.; Couture, Daniel E.; Laxton, Adrian W.; Munger-Clary, Heidi; Popli, Gautam; Sollman, Myriam J.; Whitlow, Christopher T.; Marmarelis, Vasilis Z.; Berger, Theodore W.; Deadwyler, Sam A.

    2018-06-01

    Objective. We demonstrate here the first successful implementation in humans of a proof-of-concept system for restoring and improving memory function via facilitation of memory encoding using the patient’s own hippocampal spatiotemporal neural codes for memory. Memory in humans is subject to disruption by drugs, disease and brain injury, yet previous attempts to restore or rescue memory function in humans typically involved only nonspecific, modulation of brain areas and neural systems related to memory retrieval. Approach. We have constructed a model of processes by which the hippocampus encodes memory items via spatiotemporal firing of neural ensembles that underlie the successful encoding of short-term memory. A nonlinear multi-input, multi-output (MIMO) model of hippocampal CA3 and CA1 neural firing is computed that predicts activation patterns of CA1 neurons during the encoding (sample) phase of a delayed match-to-sample (DMS) human short-term memory task. Main results. MIMO model-derived electrical stimulation delivered to the same CA1 locations during the sample phase of DMS trials facilitated short-term/working memory by 37% during the task. Longer term memory retention was also tested in the same human subjects with a delayed recognition (DR) task that utilized images from the DMS task, along with images that were not from the task. Across the subjects, the stimulated trials exhibited significant improvement (35%) in both short-term and long-term retention of visual information. Significance. These results demonstrate the facilitation of memory encoding which is an important feature for the construction of an implantable neural prosthetic to improve human memory.

  10. Convolutional Neural Networks for Human Activity Recognition Using Body-Worn Sensors

    Directory of Open Access Journals (Sweden)

    Fernando Moya Rueda

    2018-05-01

    Full Text Available Human activity recognition (HAR is a classification task for recognizing human movements. Methods of HAR are of great interest as they have become tools for measuring occurrences and durations of human actions, which are the basis of smart assistive technologies and manual processes analysis. Recently, deep neural networks have been deployed for HAR in the context of activities of daily living using multichannel time-series. These time-series are acquired from body-worn devices, which are composed of different types of sensors. The deep architectures process these measurements for finding basic and complex features in human corporal movements, and for classifying them into a set of human actions. As the devices are worn at different parts of the human body, we propose a novel deep neural network for HAR. This network handles sequence measurements from different body-worn devices separately. An evaluation of the architecture is performed on three datasets, the Oportunity, Pamap2, and an industrial dataset, outperforming the state-of-the-art. In addition, different network configurations will also be evaluated. We find that applying convolutions per sensor channel and per body-worn device improves the capabilities of convolutional neural network (CNNs.

  11. Remodeling sensory cortical maps implants specific behavioral memory.

    Science.gov (United States)

    Bieszczad, K M; Miasnikov, A A; Weinberger, N M

    2013-08-29

    Neural mechanisms underlying the capacity of memory to be rich in sensory detail are largely unknown. A candidate mechanism is learning-induced plasticity that remodels the adult sensory cortex. Here, expansion in the primary auditory cortical (A1) tonotopic map of rats was induced by pairing a 3.66-kHz tone with activation of the nucleus basalis, mimicking the effects of natural associative learning. Remodeling of A1 produced de novo specific behavioral memory, but neither memory nor plasticity was consistently at the frequency of the paired tone, which typically decreased in A1 representation. Rather, there was a specific match between individual subjects' area of expansion and the tone that was strongest in each animal's memory, as determined by post-training frequency generalization gradients. These findings provide the first demonstration of a match between the artificial induction of specific neural representational plasticity and artificial induction of behavioral memory. As such, together with prior and present findings for detection, correlation and mimicry of plasticity with the acquisition of memory, they satisfy a key criterion for neural substrates of memory. This demonstrates that directly remodeling sensory cortical maps is sufficient for the specificity of memory formation. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. The neural circuits that generate tics in Tourette's syndrome.

    Science.gov (United States)

    Wang, Zhishun; Maia, Tiago V; Marsh, Rachel; Colibazzi, Tiziano; Gerber, Andrew; Peterson, Bradley S

    2011-12-01

    The purpose of this study was to examine neural activity and connectivity within cortico-striato-thalamo-cortical circuits and to reveal circuit-based neural mechanisms that govern tic generation in Tourette's syndrome. Functional magnetic resonance imaging data were acquired from 13 individuals with Tourette's syndrome and 21 healthy comparison subjects during spontaneous or simulated tics. Independent component analysis with hierarchical partner matching was used to isolate neural activity within functionally distinct regions of cortico-striato-thalamo-cortical circuits. Granger causality was used to investigate causal interactions among these regions. The Tourette's syndrome group exhibited stronger neural activity and interregional causality than healthy comparison subjects throughout all portions of the motor pathway, including the sensorimotor cortex, putamen, pallidum, and substantia nigra. Activity in these areas correlated positively with the severity of tic symptoms. Activity within the Tourette's syndrome group was stronger during spontaneous tics than during voluntary tics in the somatosensory and posterior parietal cortices, putamen, and amygdala/hippocampus complex, suggesting that activity in these regions may represent features of the premonitory urges that generate spontaneous tic behaviors. In contrast, activity was weaker in the Tourette's syndrome group than in the healthy comparison group within portions of cortico-striato-thalamo-cortical circuits that exert top-down control over motor pathways (the caudate and anterior cingulate cortex), and progressively less activity in these regions accompanied more severe tic symptoms, suggesting that faulty activity in these circuits may result in their failure to control tic behaviors or the premonitory urges that generate them. Our findings, taken together, suggest that tics are caused by the combined effects of excessive activity in motor pathways and reduced activation in control portions of cortico-striato-thalamo-cortical

  13. The participation of cortical amygdala in innate, odor-driven behavior

    OpenAIRE

    Root, Cory M.; Denny, Christine A.; Hen, Ren?; Axel, Richard

    2014-01-01

    Innate behaviors are observed in na?ve animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviors are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centers have been anatomically defined 1-3 but the specific pathways responsible for innate responses to volatile odors have not been identified. We have devised genetic strategies that ...

  14. Adolescent cortical thickness pre- and post marijuana and alcohol initiation.

    Science.gov (United States)

    Jacobus, Joanna; Castro, Norma; Squeglia, Lindsay M; Meloy, M J; Brumback, Ty; Huestis, Marilyn A; Tapert, Susan F

    Cortical thickness abnormalities have been identified in youth using both alcohol and marijuana. However, limited studies have followed individuals pre- and post initiation of alcohol and marijuana use to help identify to what extent discrepancies in structural brain integrity are pre-existing or substance-related. Adolescents (N=69) were followed from ages 13 (pre-initiation of substance use, baseline) to ages 19 (post-initiation, follow-up). Three subgroups were identified, participants that initiated alcohol use (ALC, n=23, >20 alcohol use episodes), those that initiated both alcohol and marijuana use (ALC+MJ, n=23, >50 marijuana use episodes) and individuals that did not initiate either substance regularly by follow-up (CON, n=23, marijuana use episodes). All adolescents underwent neurocognitive testing, neuroimaging, and substance use and mental health interviews. Significant group by time interactions and main effects on cortical thickness estimates were identified for 18 cortical regions spanning the left and right hemisphere (pseffect, in cortical thickness by follow-up for individuals who have not initiated regular substance use or alcohol use only by age 19; modest between-group differences were identified at baseline in several cortical regions (ALC and CON>ALC+MJ). Minimal neurocognitive differences were observed in this sample. Findings suggest pre-existing neural differences prior to marijuana use may contribute to initiation of use and observed neural outcomes. Marijuana use may also interfere with thinning trajectories that contribute to morphological differences in young adulthood that are often observed in cross-sectional studies of heavy marijuana users. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. In our own image? Emotional and neural processing differences when observing human-human vs human-robot interactions.

    Science.gov (United States)

    Wang, Yin; Quadflieg, Susanne

    2015-11-01

    Notwithstanding the significant role that human-robot interactions (HRI) will play in the near future, limited research has explored the neural correlates of feeling eerie in response to social robots. To address this empirical lacuna, the current investigation examined brain activity using functional magnetic resonance imaging while a group of participants (n = 26) viewed a series of human-human interactions (HHI) and HRI. Although brain sites constituting the mentalizing network were found to respond to both types of interactions, systematic neural variation across sites signaled diverging social-cognitive strategies during HHI and HRI processing. Specifically, HHI elicited increased activity in the left temporal-parietal junction indicative of situation-specific mental state attributions, whereas HRI recruited the precuneus and the ventromedial prefrontal cortex (VMPFC) suggestive of script-based social reasoning. Activity in the VMPFC also tracked feelings of eeriness towards HRI in a parametric manner, revealing a potential neural correlate for a phenomenon known as the uncanny valley. By demonstrating how understanding social interactions depends on the kind of agents involved, this study highlights pivotal sub-routes of impression formation and identifies prominent challenges in the use of humanoid robots. © The Author (2015). Published by Oxford University Press.

  16. Intracerebral evidence of rhythm transform in the human auditory cortex.

    Science.gov (United States)

    Nozaradan, Sylvie; Mouraux, André; Jonas, Jacques; Colnat-Coulbois, Sophie; Rossion, Bruno; Maillard, Louis

    2017-07-01

    Musical entrainment is shared by all human cultures and the perception of a periodic beat is a cornerstone of this entrainment behavior. Here, we investigated whether beat perception might have its roots in the earliest stages of auditory cortical processing. Local field potentials were recorded from 8 patients implanted with depth-electrodes in Heschl's gyrus and the planum temporale (55 recording sites in total), usually considered as human primary and secondary auditory cortices. Using a frequency-tagging approach, we show that both low-frequency (30 Hz) neural activities in these structures faithfully track auditory rhythms through frequency-locking to the rhythm envelope. A selective gain in amplitude of the response frequency-locked to the beat frequency was observed for the low-frequency activities but not for the high-frequency activities, and was sharper in the planum temporale, especially for the more challenging syncopated rhythm. Hence, this gain process is not systematic in all activities produced in these areas and depends on the complexity of the rhythmic input. Moreover, this gain was disrupted when the rhythm was presented at fast speed, revealing low-pass response properties which could account for the propensity to perceive a beat only within the musical tempo range. Together, these observations show that, even though part of these neural transforms of rhythms could already take place in subcortical auditory processes, the earliest auditory cortical processes shape the neural representation of rhythmic inputs in favor of the emergence of a periodic beat.

  17. Mapping auditory core, lateral belt, and parabelt cortices in the human superior temporal gyrus

    DEFF Research Database (Denmark)

    Sweet, Robert A; Dorph-Petersen, Karl-Anton; Lewis, David A

    2005-01-01

    The goal of the present study was to determine whether the architectonic criteria used to identify the core, lateral belt, and parabelt auditory cortices in macaque monkeys (Macaca fascicularis) could be used to identify homologous regions in humans (Homo sapiens). Current evidence indicates...

  18. Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

    Science.gov (United States)

    Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark

    2017-09-01

    Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also

  19. Effects of Exercise in Immersive Virtual Environments on Cortical Neural Oscillations and Mental State

    Directory of Open Access Journals (Sweden)

    Tobias Vogt

    2015-01-01

    Full Text Available Virtual reality environments are increasingly being used to encourage individuals to exercise more regularly, including as part of treatment those with mental health or neurological disorders. The success of virtual environments likely depends on whether a sense of presence can be established, where participants become fully immersed in the virtual environment. Exposure to virtual environments is associated with physiological responses, including cortical activation changes. Whether the addition of a real exercise within a virtual environment alters sense of presence perception, or the accompanying physiological changes, is not known. In a randomized and controlled study design, moderate-intensity Exercise (i.e., self-paced cycling and No-Exercise (i.e., automatic propulsion trials were performed within three levels of virtual environment exposure. Each trial was 5 minutes in duration and was followed by posttrial assessments of heart rate, perceived sense of presence, EEG, and mental state. Changes in psychological strain and physical state were generally mirrored by neural activation patterns. Furthermore, these changes indicated that exercise augments the demands of virtual environment exposures and this likely contributed to an enhanced sense of presence.

  20. Neuregulin 3 Mediates Cortical Plate Invasion and Laminar Allocation of GABAergic Interneurons

    Directory of Open Access Journals (Sweden)

    Giorgia Bartolini

    2017-01-01

    Full Text Available Neural circuits in the cerebral cortex consist of excitatory pyramidal cells and inhibitory interneurons. These two main classes of cortical neurons follow largely different genetic programs, yet they assemble into highly specialized circuits during development following a very precise choreography. Previous studies have shown that signals produced by pyramidal cells influence the migration of cortical interneurons, but the molecular nature of these factors has remained elusive. Here, we identified Neuregulin 3 (Nrg3 as a chemoattractive factor expressed by developing pyramidal cells that guides the allocation of cortical interneurons in the developing cortical plate. Gain- and loss-of-function approaches reveal that Nrg3 modulates the migration of interneurons into the cortical plate in a process that is dependent on the tyrosine kinase receptor ErbB4. Perturbation of Nrg3 signaling in conditional mutants leads to abnormal lamination of cortical interneurons. Nrg3 is therefore a critical mediator in the assembly of cortical inhibitory circuits.

  1. Differentiation of insulin-producing cells from human neural progenitor cells.

    Directory of Open Access Journals (Sweden)

    Yuichi Hori

    2005-04-01

    Full Text Available BACKGROUND: Success in islet-transplantation-based therapies for type 1 diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Islets and neurons share features, including common developmental programs, and in some species brain neurons are the principal source of systemic insulin. METHODS AND FINDINGS: Here we show that brain-derived human neural progenitor cells, exposed to a series of signals that regulate in vivo pancreatic islet development, form clusters of glucose-responsive insulin-producing cells (IPCs. During in vitro differentiation of neural progenitor cells with this novel method, genes encoding essential known in vivo regulators of pancreatic islet development were expressed. Following transplantation into immunocompromised mice, IPCs released insulin C-peptide upon glucose challenge, remained differentiated, and did not form detectable tumors. CONCLUSION: Production of IPCs solely through extracellular factor modulation in the absence of genetic manipulations may promote strategies to derive transplantable islet-replacement tissues from human neural progenitor cells and other types of multipotent human stem cells.

  2. Cortical thickness in adolescent marijuana and alcohol users: A three-year prospective study from adolescence to young adulthood

    Directory of Open Access Journals (Sweden)

    Joanna Jacobus

    2015-12-01

    Full Text Available Studies suggest marijuana impacts gray and white matter neural tissue development, however few prospective studies have determined the relationship between cortical thickness and cannabis use spanning adolescence to young adulthood. This study aimed to understand how heavy marijuana use influences cortical thickness trajectories across adolescence. Subjects were adolescents with heavy marijuana use and concomitant alcohol use (MJ + ALC, n = 30 and controls (CON, n = 38 with limited substance use histories. Participants underwent magnetic resonance imaging and comprehensive substance use assessment at three independent time points. Repeated measures analysis of covariance was used to look at main effects of group, time, and Group × Time interactions on cortical thickness. MJ + ALC showed thicker cortical estimates across the brain (23 regions, particularly in frontal and parietal lobes (ps < .05. More cumulative marijuana use was associated with increased thickness estimates by 3-year follow-up (ps < .05. Heavy marijuana use during adolescence and into young adulthood may be associated with altered neural tissue development and interference with neuromaturation that can have neurobehavioral consequences. Continued follow-up of adolescent marijuana users will help understand ongoing neural changes that are associated with development of problematic use into adulthood, as well as potential for neural recovery with cessation of use.

  3. Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation

    OpenAIRE

    Mimi L. Phan; Kasia M. Bieszczad

    2016-01-01

    Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the ...

  4. Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation.

    Directory of Open Access Journals (Sweden)

    Katsuya Kobayashi

    Full Text Available Physiological high frequency activities (HFA are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections, or different terminal layers (layer IV vs. layer II/III affect its frequency, we, in the primary somatosensory cortex (SI, compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response and N80 (late response of somatosensory evoked potentials (HFA(SEP(N20 and HFA(SEP(N80 and compared those overriding N1 and N2 (first and second responses of cortico-cortical evoked potentials (HFA(CCEP(N1 and HFA(CCEP(N2. HFA(SEP(N20 showed the power peak in the frequency above 200 Hz, while HFA(CCEP(N1 had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA(CCEP(N1 and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.

  5. 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.

  6. Catecholaminergic consolidation of motor cortical neuroplasticity in humans.

    Science.gov (United States)

    Nitsche, Michael A; Grundey, Jessica; Liebetanz, David; Lang, Nicolas; Tergau, Frithjof; Paulus, Walter

    2004-11-01

    Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.

  7. Cortical thickness development of human primary visual cortex related to the age of blindness onset.

    Science.gov (United States)

    Li, Qiaojun; Song, Ming; Xu, Jiayuan; Qin, Wen; Yu, Chunshui; Jiang, Tianzi

    2017-08-01

    Blindness primarily induces structural alteration in the primary visual cortex (V1). Some studies have found that the early blind subjects had a thicker V1 compared to sighted controls, whereas late blind subjects showed no significant differences in the V1. This implies that the age of blindness onset may exert significant effects on the development of cortical thickness of the V1. However, no previous research used a trajectory of the age of blindness onset-related changes to investigate these effects. Here we explored this issue by mapping the cortical thickness trajectory of the V1 against the age of blindness onset using data from 99 blind individuals whose age of blindness onset ranged from birth to 34 years. We found that the cortical thickness of the V1 could be fitted well with a quadratic curve in both the left (F = 11.59, P = 3 × 10 -5 ) and right hemispheres (F = 6.54, P = 2 × 10 -3 ). Specifically, the cortical thickness of the V1 thinned rapidly during childhood and adolescence and did not change significantly thereafter. This trend was not observed in the primary auditory cortex (A1), primary motor cortex (M1), or primary somatosensory cortex (S1). These results provide evidence that an onset of blindness before adulthood significantly affects the cortical thickness of the V1 and suggest a critical period for cortical development of the human V1.

  8. 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

  9. Perceived stress is associated with increased rostral middle frontal gyrus cortical thickness: a family-based and discordant-sibling investigation.

    Science.gov (United States)

    Michalski, L J; Demers, C H; Baranger, D A A; Barch, D M; Harms, M P; Burgess, G C; Bogdan, R

    2017-11-01

    Elevated stress perception and depression commonly co-occur, suggesting that they share a common neurobiology. Cortical thickness of the rostral middle frontal gyrus (RMFG), a region critical for executive function, has been associated with depression- and stress-related phenotypes. Here, we examined whether RMFG cortical thickness is associated with these phenotypes in a large family-based community sample. RMFG cortical thickness was estimated using FreeSurfer among participants (n = 879) who completed the ongoing Human Connectome Project. Depression-related phenotypes (i.e. sadness, positive affect) and perceived stress were assessed via self-report. After accounting for sex, age, ethnicity, average whole-brain cortical thickness, twin status and familial structure, RMFG thickness was positively associated with perceived stress and sadness and negatively associated with positive affect at small effect sizes (accounting for 0.2-2.4% of variance; p-fdr: 0.0051-0.1900). Perceived stress was uniquely associated with RMFG thickness after accounting for depression-related phenotypes. Further, among siblings discordant for perceived stress, those reporting higher perceived stress had increased RMFG thickness (P = 4 × 10 -7 ). Lastly, RMFG thickness, perceived stress, depressive symptoms, and positive affect were all significantly heritable, with evidence of shared genetic and environmental contributions between self-report measures. Stress perception and depression share common genetic, environmental, and neural correlates. Variability in RMFG cortical thickness may play a role in stress-related depression, although effects may be small in magnitude. Prospective studies are required to examine whether variability in RMFG thickness may function as a risk factor for stress exposure and/or perception, and/or arises as a consequence of these phenotypes. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  10. Human neural progenitors express functional lysophospholipid receptors that regulate cell growth and morphology

    Directory of Open Access Journals (Sweden)

    Callihan Phillip

    2008-12-01

    Full Text Available Abstract Background Lysophospholipids regulate the morphology and growth of neurons, neural cell lines, and neural progenitors. A stable human neural progenitor cell line is not currently available in which to study the role of lysophospholipids in human neural development. We recently established a stable, adherent human embryonic stem cell-derived neuroepithelial (hES-NEP cell line which recapitulates morphological and phenotypic features of neural progenitor cells isolated from fetal tissue. The goal of this study was to determine if hES-NEP cells express functional lysophospholipid receptors, and if activation of these receptors mediates cellular responses critical for neural development. Results Our results demonstrate that Lysophosphatidic Acid (LPA and Sphingosine-1-phosphate (S1P receptors are functionally expressed in hES-NEP cells and are coupled to multiple cellular signaling pathways. We have shown that transcript levels for S1P1 receptor increased significantly in the transition from embryonic stem cell to hES-NEP. hES-NEP cells express LPA and S1P receptors coupled to Gi/o G-proteins that inhibit adenylyl cyclase and to Gq-like phospholipase C activity. LPA and S1P also induce p44/42 ERK MAP kinase phosphorylation in these cells and stimulate cell proliferation via Gi/o coupled receptors in an Epidermal Growth Factor Receptor (EGFR- and ERK-dependent pathway. In contrast, LPA and S1P stimulate transient cell rounding and aggregation that is independent of EGFR and ERK, but dependent on the Rho effector p160 ROCK. Conclusion Thus, lysophospholipids regulate neural progenitor growth and morphology through distinct mechanisms. These findings establish human ES cell-derived NEP cells as a model system for studying the role of lysophospholipids in neural progenitors.

  11. Development of global cortical networks in early infancy.

    Science.gov (United States)

    Homae, Fumitaka; Watanabe, Hama; Otobe, Takayuki; Nakano, Tamami; Go, Tohshin; Konishi, Yukuo; Taga, Gentaro

    2010-04-07

    Human cognition and behaviors are subserved by global networks of neural mechanisms. Although the organization of the brain is a subject of interest, the process of development of global cortical networks in early infancy has not yet been clarified. In the present study, we explored developmental changes in these networks from several days to 6 months after birth by examining spontaneous fluctuations in brain activity, using multichannel near-infrared spectroscopy. We set up 94 measurement channels over the frontal, temporal, parietal, and occipital regions of the infant brain. The obtained signals showed complex time-series properties, which were characterized as 1/f fluctuations. To reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of continuous signals between all the pairs of measurement channels. We found that the cortical network organization showed regional dependency and dynamic changes in the course of development. In the temporal, parietal, and occipital regions, connectivity increased between homologous regions in the two hemispheres and within hemispheres; in the frontal regions, it decreased progressively. Frontoposterior connectivity changed to a "U-shaped" pattern within 6 months: it decreases from the neonatal period to the age of 3 months and increases from the age of 3 months to the age of 6 months. We applied cluster analyses to the correlation coefficients and showed that the bilateral organization of the networks begins to emerge during the first 3 months of life. Our findings suggest that these developing networks, which form multiple clusters, are precursors of the functional cerebral architecture.

  12. Neural mechanisms underlying catastrophic failure in human-machine interaction during aerial navigation

    Science.gov (United States)

    Saproo, Sameer; Shih, Victor; Jangraw, David C.; Sajda, Paul

    2016-12-01

    Objective. We investigated the neural correlates of workload buildup in a fine visuomotor task called the boundary avoidance task (BAT). The BAT has been known to induce naturally occurring failures of human-machine coupling in high performance aircraft that can potentially lead to a crash—these failures are termed pilot induced oscillations (PIOs). Approach. We recorded EEG and pupillometry data from human subjects engaged in a flight BAT simulated within a virtual 3D environment. Main results. We find that workload buildup in a BAT can be successfully decoded from oscillatory features in the electroencephalogram (EEG). Information in delta, theta, alpha, beta, and gamma spectral bands of the EEG all contribute to successful decoding, however gamma band activity with a lateralized somatosensory topography has the highest contribution, while theta band activity with a fronto-central topography has the most robust contribution in terms of real-world usability. We show that the output of the spectral decoder can be used to predict PIO susceptibility. We also find that workload buildup in the task induces pupil dilation, the magnitude of which is significantly correlated with the magnitude of the decoded EEG signals. These results suggest that PIOs may result from the dysregulation of cortical networks such as the locus coeruleus (LC)—anterior cingulate cortex (ACC) circuit. Significance. Our findings may generalize to similar control failures in other cases of tight man-machine coupling where gains and latencies in the control system must be inferred and compensated for by the human operators. A closed-loop intervention using neurophysiological decoding of workload buildup that targets the LC-ACC circuit may positively impact operator performance in such situations.

  13. Intrinsic connectivity of neural networks in the awake rabbit.

    Science.gov (United States)

    Schroeder, Matthew P; Weiss, Craig; Procissi, Daniel; Disterhoft, John F; Wang, Lei

    2016-04-01

    The way in which the brain is functionally connected into different networks has emerged as an important research topic in order to understand normal neural processing and signaling. Since some experimental manipulations are difficult or unethical to perform in humans, animal models are better suited to investigate this topic. Rabbits are a species that can undergo MRI scanning in an awake and conscious state with minimal preparation and habituation. In this study, we characterized the intrinsic functional networks of the resting New Zealand White rabbit brain using BOLD fMRI data. Group independent component analysis revealed seven networks similar to those previously found in humans, non-human primates and/or rodents including the hippocampus, default mode, cerebellum, thalamus, and visual, somatosensory, and parietal cortices. For the first time, the intrinsic functional networks of the resting rabbit brain have been elucidated demonstrating the rabbit's applicability as a translational animal model. Without the confounding effects of anesthetics or sedatives, future experiments may employ rabbits to understand changes in neural connectivity and brain functioning as a result of experimental manipulation (e.g., temporary or permanent network disruption, learning-related changes, and drug administration). Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Cortical pitch regions in humans respond primarily to resolved harmonics and are located in specific tonotopic regions of anterior auditory cortex.

    Science.gov (United States)

    Norman-Haignere, Sam; Kanwisher, Nancy; McDermott, Josh H

    2013-12-11

    Pitch is a defining perceptual property of many real-world sounds, including music and speech. Classically, theories of pitch perception have differentiated between temporal and spectral cues. These cues are rendered distinct by the frequency resolution of the ear, such that some frequencies produce "resolved" peaks of excitation in the cochlea, whereas others are "unresolved," providing a pitch cue only via their temporal fluctuations. Despite longstanding interest, the neural structures that process pitch, and their relationship to these cues, have remained controversial. Here, using fMRI in humans, we report the following: (1) consistent with previous reports, all subjects exhibited pitch-sensitive cortical regions that responded substantially more to harmonic tones than frequency-matched noise; (2) the response of these regions was mainly driven by spectrally resolved harmonics, although they also exhibited a weak but consistent response to unresolved harmonics relative to noise; (3) the response of pitch-sensitive regions to a parametric manipulation of resolvability tracked psychophysical discrimination thresholds for the same stimuli; and (4) pitch-sensitive regions were localized to specific tonotopic regions of anterior auditory cortex, extending from a low-frequency region of primary auditory cortex into a more anterior and less frequency-selective region of nonprimary auditory cortex. These results demonstrate that cortical pitch responses are located in a stereotyped region of anterior auditory cortex and are predominantly driven by resolved frequency components in a way that mirrors behavior.

  15. On the homogeneity and heterogeneity of cortical thickness profiles in Homo sapiens sapiens.

    Science.gov (United States)

    Koten, Jan Willem; Schüppen, André; Morozova, Maria; Lehofer, Agnes; Koschutnig, Karl; Wood, Guilherme

    2017-12-20

    Cortical thickness has been investigated since the beginning of the 20th century, but we do not know how similar the cortical thickness profiles among humans are. In this study, the local similarity of cortical thickness profiles was investigated using sliding window methods. Here, we show that approximately 5% of the cortical thickness profiles are similarly expressed among humans while 45% of the cortical thickness profiles show a high level of heterogeneity. Therefore, heterogeneity is the rule, not the exception. Cortical thickness profiles of somatosensory homunculi and the anterior insula are consistent among humans, while the cortical thickness profiles of the motor homunculus are more variable. Cortical thickness profiles of homunculi that code for muscle position and skin stimulation are highly similar among humans despite large differences in sex, education, and age. This finding suggests that the structure of these cortices remains well preserved over a lifetime. Our observations possibly relativize opinions on cortical plasticity.

  16. Aging and Fracture of Human Cortical Bone and Tooth Dentin

    Energy Technology Data Exchange (ETDEWEB)

    Ager, Joel; Koester, Kurt J.; Ager III, Joel W.; Ritchie, Robert O.

    2008-05-07

    Mineralized tissues, such as bone and tooth dentin, serve as structural materials in the human body and, as such, have evolved to resist fracture. In assessing their quantitative fracture resistance or toughness, it is important to distinguish between intrinsic toughening mechanisms which function ahead of the crack tip, such as plasticity in metals, and extrinsic mechanisms which function primarily behind the tip, such as crack bridging in ceramics. Bone and dentin derive their resistance to fracture principally from extrinsic toughening mechanisms which have their origins in the hierarchical microstructure of these mineralized tissues. Experimentally, quantification of these toughening mechanisms requires a crack-growth resistance approach, which can be achieved by measuring the crack-driving force, e.g., the stress intensity, as a function of crack extension ("R-curve approach"). Here this methodology is used to study of the effect of aging on the fracture properties of human cortical bone and human dentin in order to discern the microstructural origins of toughness in these materials.

  17. How Visual Cortical Organization Is Altered by Ophthalmologic and Neurologic Disorders

    NARCIS (Netherlands)

    Dumoulin, Serge O; Knapen, Tomas

    2018-01-01

    Receptive fields are a core property of cortical organization. Modern neuroimaging allows routine access to visual population receptive fields (pRFs), enabling investigations of clinical disorders. Yet how the underlying neural circuitry operates is controversial. The controversy surrounds

  18. Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion.

    Science.gov (United States)

    Lee, A Moses; Hoy, Jennifer L; Bonci, Antonello; Wilbrecht, Linda; Stryker, Michael P; Niell, Cristopher M

    2014-07-16

    Sensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR's effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Somatostatin-expressing inhibitory interneurons in cortical circuits

    Directory of Open Access Journals (Sweden)

    Iryna Yavorska

    2016-09-01

    Full Text Available Cortical inhibitory neurons exhibit remarkable diversity in their morphology, connectivity, and synaptic properties. Here, we review the function of somatostatin-expressing (SOM inhibitory interneurons, focusing largely on sensory cortex. SOM neurons also comprise a number of subpopulations that can be distinguished by their morphology, input and output connectivity, laminar location, firing properties, and expression of molecular markers. Several of these classes of SOM neurons show unique dynamics and characteristics, such as facilitating synapses, specific axonal projections, intralaminar input, and top-down modulation, which suggest possible computational roles. SOM cells can be differentially modulated by behavioral state depending on their class, sensory system, and behavioral paradigm. The functional effects of such modulation have been studied with optogenetic manipulation of SOM cells, which produces effects on learning and memory, task performance, and the integration of cortical activity. Different classes of SOM cells participate in distinct disinhibitory circuits with different inhibitory partners and in different cortical layers. Through these disinhibitory circuits, SOM cells help encode the behavioral relevance of sensory stimuli by regulating the activity of cortical neurons based on subcortical and intracortical modulatory input. Associative learning leads to long-term changes in the strength of connectivity of SOM cells with other neurons, often influencing the strength of inhibitory input they receive. Thus despite their heterogeneity and variability across cortical areas, current evidence shows that SOM neurons perform unique neural computations, forming not only distinct molecular but also functional subclasses of cortical inhibitory interneurons.

  20. Lateralization of the human mirror neuron system.

    Science.gov (United States)

    Aziz-Zadeh, Lisa; Koski, Lisa; Zaidel, Eran; Mazziotta, John; Iacoboni, Marco

    2006-03-15

    A cortical network consisting of the inferior frontal, rostral inferior parietal, and posterior superior temporal cortices has been implicated in representing actions in the primate brain and is critical to imitation in humans. This neural circuitry may be an evolutionary precursor of neural systems associated with language. However, language is predominantly lateralized to the left hemisphere, whereas the degree of lateralization of the imitation circuitry in humans is unclear. We conducted a functional magnetic resonance imaging study of imitation of finger movements with lateralized stimuli and responses. During imitation, activity in the inferior frontal and rostral inferior parietal cortex, although fairly bilateral, was stronger in the hemisphere ipsilateral to the visual stimulus and response hand. This ipsilateral pattern is at variance with the typical contralateral activity of primary visual and motor areas. Reliably increased signal in the right superior temporal sulcus (STS) was observed for both left-sided and right-sided imitation tasks, although subthreshold activity was also observed in the left STS. Overall, the data indicate that visual and motor components of the human mirror system are not left-lateralized. The left hemisphere superiority for language, then, must be have been favored by other types of language precursors, perhaps auditory or multimodal action representations.

  1. The neural basis of suppression and amblyopia in strabismus.

    Science.gov (United States)

    Sengpiel, F; Blakemore, C

    1996-01-01

    The neurophysiological consequences of artificial strabismus in cats and monkeys have been studied for 30 years. However, until very recently no clear picture has emerged of neural deficits that might account for the powerful interocular suppression that strabismic humans experience, nor for the severe amblyopia that is often associated with convergent strabismus. Here we review the effects of squint on the integrative capacities of the primary visual cortex and propose a hypothesis about the relationship between suppression and amblyopia. Most neurons in the visual cortex of normal cats and monkeys can be excited through either eye and show strong facilitation during binocular stimulation with contours of similar orientation in the two eyes. But in strabismic animals, cortical neurons tend to fall into two populations of monocularly excitable cells and exhibit suppressive binocular interactions that share key properties with perceptual suppression in strabismic humans. Such interocular suppression, if prolonged and asymmetric (with input from the squinting eye habitually suppressed by that from the fixating eye), might lead to neural defects in the representation of the deviating eye and hence to amblyopia.

  2. The effect of early visual deprivation on the neural bases of multisensory processing.

    Science.gov (United States)

    Guerreiro, Maria J S; Putzar, Lisa; Röder, Brigitte

    2015-06-01

    Developmental vision is deemed to be necessary for the maturation of multisensory cortical circuits. Thus far, this has only been investigated in animal studies, which have shown that congenital visual deprivation markedly reduces the capability of neurons to integrate cross-modal inputs. The present study investigated the effect of transient congenital visual deprivation on the neural mechanisms of multisensory processing in humans. We used functional magnetic resonance imaging to compare responses of visual and auditory cortical areas to visual, auditory and audio-visual stimulation in cataract-reversal patients and normally sighted controls. The results showed that cataract-reversal patients, unlike normally sighted controls, did not exhibit multisensory integration in auditory areas. Furthermore, cataract-reversal patients, but not normally sighted controls, exhibited lower visual cortical processing within visual cortex during audio-visual stimulation than during visual stimulation. These results indicate that congenital visual deprivation affects the capability of cortical areas to integrate cross-modal inputs in humans, possibly because visual processing is suppressed during cross-modal stimulation. Arguably, the lack of vision in the first months after birth may result in a reorganization of visual cortex, including the suppression of noisy visual input from the deprived retina in order to reduce interference during auditory processing. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Altered topology of neural circuits in congenital prosopagnosia.

    Science.gov (United States)

    Rosenthal, Gideon; Tanzer, Michal; Simony, Erez; Hasson, Uri; Behrmann, Marlene; Avidan, Galia

    2017-08-21

    Using a novel, fMRI-based inter-subject functional correlation (ISFC) approach, which isolates stimulus-locked inter-regional correlation patterns, we compared the cortical topology of the neural circuit for face processing in participants with an impairment in face recognition, congenital prosopagnosia (CP), and matched controls. Whereas the anterior temporal lobe served as the major network hub for face processing in controls, this was not the case for the CPs. Instead, this group evinced hyper-connectivity in posterior regions of the visual cortex, mostly associated with the lateral occipital and the inferior temporal cortices. Moreover, the extent of this hyper-connectivity was correlated with the face recognition deficit. These results offer new insights into the perturbed cortical topology in CP, which may serve as the underlying neural basis of the behavioral deficits typical of this disorder. The approach adopted here has the potential to uncover altered topologies in other neurodevelopmental disorders, as well.

  4. Neural Correlates of Body and Face Perception Following Bilateral Destruction of the Primary Visual Cortices

    Directory of Open Access Journals (Sweden)

    Jan eVan den Stock

    2014-02-01

    Full Text Available Non-conscious visual processing of different object categories was investigated in a rare patient with bilateral destruction of the visual cortex (V1 and clinical blindness over the entire visual field. Images of biological and non-biological object categories were presented consisting of human bodies, faces, butterflies, cars, and scrambles. Behaviorally, only the body shape induced higher perceptual sensitivity, as revealed by signal detection analysis. Passive exposure to bodies and faces activated amygdala and superior temporal sulcus. In addition, bodies also activated the extrastriate body area, insula, orbitofrontal cortex (OFC and cerebellum. The results show that following bilateral damage to the primary visual cortex and ensuing complete cortical blindness, the human visual system is able to process categorical properties of human body shapes. This residual vision may be based on V1-independent input to body-selective areas along the ventral stream, in concert with areas involved in the representation of bodily states, like insula, OFC and cerebellum.

  5. Towards an optimal paradigm for simultaneously recording cortical and brainstem auditory evoked potentials.

    Science.gov (United States)

    Bidelman, Gavin M

    2015-02-15

    Simultaneous recording of brainstem and cortical event-related brain potentials (ERPs) may offer a valuable tool for understanding the early neural transcription of behaviorally relevant sounds and the hierarchy of signal processing operating at multiple levels of the auditory system. To date, dual recordings have been challenged by technological and physiological limitations including different optimal parameters necessary to elicit each class of ERP (e.g., differential adaptation/habitation effects and number of trials to obtain adequate response signal-to-noise ratio). We investigated a new stimulus paradigm for concurrent recording of the auditory brainstem frequency-following response (FFR) and cortical ERPs. The paradigm is "optimal" in that it uses a clustered stimulus presentation and variable interstimulus interval (ISI) to (i) achieve the most ideal acquisition parameters for eliciting subcortical and cortical responses, (ii) obtain an adequate number of trials to detect each class of response, and (iii) minimize neural adaptation/habituation effects. Comparison between clustered and traditional (fixed, slow ISI) stimulus paradigms revealed minimal change in amplitude or latencies of either the brainstem FFR or cortical ERP. The clustered paradigm offered over a 3× increase in recording efficiency compared to conventional (fixed ISI presentation) and thus, a more rapid protocol for obtaining dual brainstem-cortical recordings in individual listeners. We infer that faster recording of subcortical and cortical potentials might allow more complete and sensitive testing of neurophysiological function and aid in the differential assessment of auditory function. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. The artist emerges: visual art learning alters neural structure and function.

    Science.gov (United States)

    Schlegel, Alexander; Alexander, Prescott; Fogelson, Sergey V; Li, Xueting; Lu, Zhengang; Kohler, Peter J; Riley, Enrico; Tse, Peter U; Meng, Ming

    2015-01-15

    How does the brain mediate visual artistic creativity? Here we studied behavioral and neural changes in drawing and painting students compared to students who did not study art. We investigated three aspects of cognition vital to many visual artists: creative cognition, perception, and perception-to-action. We found that the art students became more creative via the reorganization of prefrontal white matter but did not find any significant changes in perceptual ability or related neural activity in the art students relative to the control group. Moreover, the art students improved in their ability to sketch human figures from observation, and multivariate patterns of cortical and cerebellar activity evoked by this drawing task became increasingly separable between art and non-art students. Our findings suggest that the emergence of visual artistic skills is supported by plasticity in neural pathways that enable creative cognition and mediate perceptuomotor integration. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Common cortical responses evoked by appearance, disappearance and change of the human face

    Directory of Open Access Journals (Sweden)

    Kida Tetsuo

    2009-04-01

    Full Text Available Abstract Background To segregate luminance-related, face-related and non-specific components involved in spatio-temporal dynamics of cortical activations to a face stimulus, we recorded cortical responses to face appearance (Onset, disappearance (Offset, and change (Change using magnetoencephalography. Results Activity in and around the primary visual cortex (V1/V2 showed luminance-dependent behavior. Any of the three events evoked activity in the middle occipital gyrus (MOG at 150 ms and temporo-parietal junction (TPJ at 250 ms after the onset of each event. Onset and Change activated the fusiform gyrus (FG, while Offset did not. This FG activation showed a triphasic waveform, consistent with results of intracranial recordings in humans. Conclusion Analysis employed in this study successfully segregated four different elements involved in the spatio-temporal dynamics of cortical activations in response to a face stimulus. The results show the responses of MOG and TPJ to be associated with non-specific processes, such as the detection of abrupt changes or exogenous attention. Activity in FG corresponds to a face-specific response recorded by intracranial studies, and that in V1/V2 is related to a change in luminance.

  8. 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 ...

  9. An anatomical and functional topography of human auditory cortical areas

    Directory of Open Access Journals (Sweden)

    Michelle eMoerel

    2014-07-01

    Full Text Available While advances in magnetic resonance imaging (MRI throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla. Importantly, we illustrate that - whereas a group-based approach to analyze functional (tonotopic maps is appropriate to highlight the main tonotopic axis - the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e. myelination as well as of functional properties (e.g. broadness of frequency tuning is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions.

  10. The Neural Circuits that Generate Tics in Gilles de la Tourette Syndrome

    Science.gov (United States)

    Wang, Zhishun; Maia, Tiago V.; Marsh, Rachel; Colibazzi, Tiziano; Gerber, Andrew; Peterson, Bradley S.

    2014-01-01

    Objective To study neural activity and connectivity within cortico-striato-thalamo-cortical circuits and to reveal circuit-based neural mechanisms that govern tic generation in Tourette syndrome. Method We acquired fMRI data from 13 participants with Tourette syndrome and 21 controls during spontaneous or simulated tics. We used independent component analysis with hierarchical partner matching to isolate neural activity within functionally distinct regions of cortico-striato-thalamo-cortical circuits. We used Granger causality to investigate causal interactions among these regions. Results We found that the Tourette group exhibited stronger neural activity and interregional causality than controls throughout all portions of the motor pathway including sensorimotor cortex, putamen, pallidum, and substania nigra. Activity in these areas correlated positively with the severity of tic symptoms. Activity within the Tourette group was stronger during spontaneous tics than during voluntary tics in somatosensory and posterior parietal cortices, putamen, and amygdala/hippocampus complex, suggesting that activity in these regions may represent features of the premonitory urges that generate spontaneous tic behaviors. In contrast, activity was weaker in the Tourette group than in controls within portions of cortico-striato-thalamo-cortical circuits that exert top-down control over motor pathways (caudate and anterior cingulate cortex), and progressively less activity in these regions accompanied more severe tic symptoms, suggesting that faulty activity in these circuits may fail to control tic behaviors or the premonitory urges that generate them. Conclusions Our findings taken together suggest that tics are caused by the combined effects of excessive activity in motor pathways and reduced activation in control portions of cortico-striato-thalamo-cortical circuits. PMID:21955933

  11. Neural fields theory and applications

    CERN Document Server

    Graben, Peter; Potthast, Roland; Wright, James

    2014-01-01

    With this book, the editors present the first comprehensive collection in neural field studies, authored by leading scientists in the field - among them are two of the founding-fathers of neural field theory. Up to now, research results in the field have been disseminated across a number of distinct journals from mathematics, computational neuroscience, biophysics, cognitive science and others. Starting with a tutorial for novices in neural field studies, the book comprises chapters on emergent patterns, their phase transitions and evolution, on stochastic approaches, cortical development, cognition, robotics and computation, large-scale numerical simulations, the coupling of neural fields to the electroencephalogram and phase transitions in anesthesia. The intended readership are students and scientists in applied mathematics, theoretical physics, theoretical biology, and computational neuroscience. Neural field theory and its applications have a long-standing tradition in the mathematical and computational ...

  12. Noise exposure alters long-term neural firing rates and synchrony in primary auditory and rostral belt cortices following bimodal stimulation.

    Science.gov (United States)

    Takacs, Joseph D; Forrest, Taylor J; Basura, Gregory J

    2017-12-01

    We previously demonstrated that bimodal stimulation (spinal trigeminal nucleus [Sp5] paired with best frequency tone) altered neural tone-evoked and spontaneous firing rates (SFRs) in primary auditory cortex (A1) 15 min after pairing in guinea pigs with and without noise-induced tinnitus. Neural responses were enhanced (+10 ms) or suppressed (0 ms) based on the bimodal pairing interval. Here we investigated whether bimodal stimulation leads to long-term (up to 2 h) changes in tone-evoked and SFRs and neural synchrony (correlate of tinnitus) and if the long-term bimodal effects are altered following noise exposure. To obviate the effects of permanent hearing loss on the results, firing rates and neural synchrony were measured three weeks following unilateral (left ear) noise exposure and a temporary threshold shift. Simultaneous extra-cellular single-unit recordings were made from contralateral (to noise) A1 and dorsal rostral belt (RB); an associative auditory cortical region thought to influence A1, before and after bimodal stimulation (pairing intervals of 0 ms; simultaneous Sp5-tone and +10 ms; Sp5 precedes tone). Sixty and 120 min after 0 ms pairing tone-evoked and SFRs were suppressed in sham A1; an effect only preserved 120 min following pairing in noise. Stimulation at +10 ms only affected SFRs 120 min after pairing in sham and noise-exposed A1. Within sham RB, pairing at 0 and +10 ms persistently suppressed tone-evoked and SFRs, while 0 ms pairing in noise markedly enhanced tone-evoked and SFRs up to 2 h. Together, these findings suggest that bimodal stimulation has long-lasting effects in A1 that also extend to the associative RB that is altered by noise and may have persistent implications for how noise damaged brains process multi-sensory information. Moreover, prior to bimodal stimulation, noise damage increased neural synchrony in A1, RB and between A1 and RB neurons. Bimodal stimulation led to persistent changes in neural synchrony in

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

    Science.gov (United States)

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

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

  14. Music-induced cortical plasticity and lateral inhibition in the human auditory cortex as foundations for tonal tinnitus treatment.

    Science.gov (United States)

    Pantev, Christo; Okamoto, Hidehiko; Teismann, Henning

    2012-01-01

    Over the past 15 years, we have studied plasticity in the human auditory cortex by means of magnetoencephalography (MEG). Two main topics nurtured our curiosity: the effects of musical training on plasticity in the auditory system, and the effects of lateral inhibition. One of our plasticity studies found that listening to notched music for 3 h inhibited the neuronal activity in the auditory cortex that corresponded to the center-frequency of the notch, suggesting suppression of neural activity by lateral inhibition. Subsequent research on this topic found that suppression was notably dependent upon the notch width employed, that the lower notch-edge induced stronger attenuation of neural activity than the higher notch-edge, and that auditory focused attention strengthened the inhibitory networks. Crucially, the overall effects of lateral inhibition on human auditory cortical activity were stronger than the habituation effects. Based on these results we developed a novel treatment strategy for tonal tinnitus-tailor-made notched music training (TMNMT). By notching the music energy spectrum around the individual tinnitus frequency, we intended to attract lateral inhibition to auditory neurons involved in tinnitus perception. So far, the training strategy has been evaluated in two studies. The results of the initial long-term controlled study (12 months) supported the validity of the treatment concept: subjective tinnitus loudness and annoyance were significantly reduced after TMNMT but not when notching spared the tinnitus frequencies. Correspondingly, tinnitus-related auditory evoked fields (AEFs) were significantly reduced after training. The subsequent short-term (5 days) training study indicated that training was more effective in the case of tinnitus frequencies ≤ 8 kHz compared to tinnitus frequencies >8 kHz, and that training should be employed over a long-term in order to induce more persistent effects. Further development and evaluation of TMNMT therapy

  15. The effect of the neural activity on topological properties of growing neural networks.

    Science.gov (United States)

    Gafarov, F M; Gafarova, V R

    2016-09-01

    The connectivity structure in cortical networks defines how information is transmitted and processed, and it is a source of the complex spatiotemporal patterns of network's development, and the process of creation and deletion of connections is continuous in the whole life of the organism. In this paper, we study how neural activity influences the growth process in neural networks. By using a two-dimensional activity-dependent growth model we demonstrated the neural network growth process from disconnected neurons to fully connected networks. For making quantitative investigation of the network's activity influence on its topological properties we compared it with the random growth network not depending on network's activity. By using the random graphs theory methods for the analysis of the network's connections structure it is shown that the growth in neural networks results in the formation of a well-known "small-world" network.

  16. Model cortical association fields account for the time course and dependence on target complexity of human contour perception.

    Directory of Open Access Journals (Sweden)

    Vadas Gintautas

    2011-10-01

    Full Text Available Can lateral connectivity in the primary visual cortex account for the time dependence and intrinsic task difficulty of human contour detection? To answer this question, we created a synthetic image set that prevents sole reliance on either low-level visual features or high-level context for the detection of target objects. Rendered images consist of smoothly varying, globally aligned contour fragments (amoebas distributed among groups of randomly rotated fragments (clutter. The time course and accuracy of amoeba detection by humans was measured using a two-alternative forced choice protocol with self-reported confidence and variable image presentation time (20-200 ms, followed by an image mask optimized so as to interrupt visual processing. Measured psychometric functions were well fit by sigmoidal functions with exponential time constants of 30-91 ms, depending on amoeba complexity. Key aspects of the psychophysical experiments were accounted for by a computational network model, in which simulated responses across retinotopic arrays of orientation-selective elements were modulated by cortical association fields, represented as multiplicative kernels computed from the differences in pairwise edge statistics between target and distractor images. Comparing the experimental and the computational results suggests that each iteration of the lateral interactions takes at least [Formula: see text] ms of cortical processing time. Our results provide evidence that cortical association fields between orientation selective elements in early visual areas can account for important temporal and task-dependent aspects of the psychometric curves characterizing human contour perception, with the remaining discrepancies postulated to arise from the influence of higher cortical areas.

  17. Human Embryonic Stem Cells: A Model for the Study of Neural Development and Neurological Diseases

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    Piya Prajumwongs

    2016-01-01

    Full Text Available Although the mechanism of neurogenesis has been well documented in other organisms, there might be fundamental differences between human and those species referring to species-specific context. Based on principles learned from other systems, it is found that the signaling pathways required for neural induction and specification of human embryonic stem cells (hESCs recapitulated those in the early embryo development in vivo at certain degree. This underscores the usefulness of hESCs in understanding early human neural development and reinforces the need to integrate the principles of developmental biology and hESC biology for an efficient neural differentiation.

  18. The neural basis of task switching changes with skill acquisition

    Directory of Open Access Journals (Sweden)

    Koji eJimura

    2014-05-01

    Full Text Available Learning novel skills involves reorganization and optimization of cognitive processing involving a broad network of brain regions. Previous work has shown asymmetric costs of switching to a well-trained task versus a poorly-trained task, but the neural basis of these differential switch costs is unclear. The current study examined the neural signature of task switching in the context of acquisition of new skill. Human participants alternated randomly between a novel visual task (mirror-reversed word reading and a highly practiced one (plain word reading, allowing the isolation of task switching and skill set maintenance. Two scan sessions were separated by two weeks, with behavioral training on the mirror reading task in between the two sessions. Broad cortical regions, including bilateral prefrontal, parietal, and extrastriate cortices, showed decreased activity associated with learning of the mirror reading skill. In contrast, learning to switch to the novel skill was associated with decreased activity in a focal subcortical region in the dorsal striatum. Switching to the highly practiced task was associated with a non-overlapping set of regions, suggesting substantial differences in the neural substrates of switching as a function of task skill. Searchlight multivariate pattern analysis also revealed that learning was associated with decreased pattern information for mirror versus plain reading tasks in fronto-parietal regions. Inferior frontal junction and posterior parietal cortex showed a joint effect of univariate activation and pattern information. These results suggest distinct learning mechanisms task performance and executive control as a function of learning.

  19. A Neural Theory of Visual Attention: Bridging Cognition and Neurophysiology

    Science.gov (United States)

    Bundesen, Claus; Habekost, Thomas; Kyllingsbaek, Soren

    2005-01-01

    A neural theory of visual attention (NTVA) is presented. NTVA is a neural interpretation of C. Bundesen's (1990) theory of visual attention (TVA). In NTVA, visual processing capacity is distributed across stimuli by dynamic remapping of receptive fields of cortical cells such that more processing resources (cells) are devoted to behaviorally…

  20. Hippocampal-cortical contributions to strategic exploration during perceptual discrimination.

    Science.gov (United States)

    Voss, Joel L; Cohen, Neal J

    2017-06-01

    The hippocampus is crucial for long-term memory; its involvement in short-term or immediate expressions of memory is more controversial. Rodent hippocampus has been implicated in an expression of memory that occurs on-line during exploration termed "vicarious trial-and-error" (VTE) behavior. VTE occurs when rodents iteratively explore options during perceptual discrimination or at choice points. It is strategic in that it accelerates learning and improves later memory. VTE has been associated with activity of rodent hippocampal neurons, and lesions of hippocampus disrupt VTE and associated learning and memory advantages. Analogous findings of VTE in humans would support the role of hippocampus in active use of short-term memory to guide strategic behavior. We therefore measured VTE using eye-movement tracking during perceptual discrimination and identified relevant neural correlates with functional magnetic resonance imaging. A difficult perceptual-discrimination task was used that required visual information to be maintained during a several second trial, but with no long-term memory component. VTE accelerated discrimination. Neural correlates of VTE included robust activity of hippocampus and activity of a network of medial prefrontal and lateral parietal regions involved in memory-guided behavior. This VTE-related activity was distinct from activity associated with simply viewing visual stimuli and making eye movements during the discrimination task, which occurred in regions frequently associated with visual processing and eye-movement control. Subjects were mostly unaware of performing VTE, thus further distancing VTE from explicit long-term memory processing. These findings bridge the rodent and human literatures on neural substrates of memory-guided behavior, and provide further support for the role of hippocampus and a hippocampal-centered network of cortical regions in the immediate use of memory in on-line processing and the guidance of behavior. © 2017

  1. Combined small-molecule inhibition accelerates the derivation of functional, early-born, cortical neurons from human pluripotent stem cells

    Science.gov (United States)

    Qi, Yuchen; Zhang, Xin-Jun; Renier, Nicolas; Wu, Zhuhao; Atkin, Talia; Sun, Ziyi; Ozair, M. Zeeshan; Tchieu, Jason; Zimmer, Bastian; Fattahi, Faranak; Ganat, Yosif; Azevedo, Ricardo; Zeltner, Nadja; Brivanlou, Ali H.; Karayiorgou, Maria; Gogos, Joseph; Tomishima, Mark; Tessier-Lavigne, Marc; Shi, Song-Hai; Studer, Lorenz

    2017-01-01

    Considerable progress has been made in converting human pluripotent stem cells (hPSCs) into functional neurons. However, the protracted timing of human neuron specification and functional maturation remains a key challenge that hampers the routine application of hPSC-derived lineages in disease modeling and regenerative medicine. Using a combinatorial small-molecule screen, we previously identified conditions for the rapid differentiation of hPSCs into peripheral sensory neurons. Here we generalize the approach to central nervous system (CNS) fates by developing a small-molecule approach for accelerated induction of early-born cortical neurons. Combinatorial application of 6 pathway inhibitors induces post-mitotic cortical neurons with functional electrophysiological properties by day 16 of differentiation, in the absence of glial cell co-culture. The resulting neurons, transplanted at 8 days of differentiation into the postnatal mouse cortex, are functional and establish long-distance projections, as shown using iDISCO whole brain imaging. Accelerated differentiation into cortical neuron fates should facilitate hPSC-based strategies for disease modeling and cell therapy in CNS disorders. PMID:28112759

  2. Neural Correlates of the Cortisol Awakening Response in Humans.

    Science.gov (United States)

    Boehringer, Andreas; Tost, Heike; Haddad, Leila; Lederbogen, Florian; Wüst, Stefan; Schwarz, Emanuel; Meyer-Lindenberg, Andreas

    2015-08-01

    The cortisol rise after awakening (cortisol awakening response, CAR) is a core biomarker of hypothalamic-pituitary-adrenal (HPA) axis regulation related to psychosocial stress and stress-related psychiatric disorders. However, the neural regulation of the CAR has not been examined in humans. Here, we studied neural regulation related to the CAR in a sample of 25 healthy human participants using an established psychosocial stress paradigm together with multimodal functional and structural (voxel-based morphometry) magnetic resonance imaging. Across subjects, a smaller CAR was associated with reduced grey matter volume and increased stress-related brain activity in the perigenual ACC, a region which inhibits HPA axis activity during stress that is implicated in risk mechanisms and pathophysiology of stress-related mental diseases. Moreover, functional connectivity between the perigenual ACC and the hypothalamus, the primary controller of HPA axis activity, was associated with the CAR. Our findings provide support for a role of the perigenual ACC in regulating the CAR in humans and may aid future research on the pathophysiology of stress-related illnesses, such as depression, and environmental risk for illnesses such as schizophrenia.

  3. Cerebellar Shaping of Motor Cortical Firing Is Correlated with Timing of Motor Actions

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    Abdulraheem Nashef

    2018-05-01

    Full Text Available Summary: In higher mammals, motor timing is considered to be dictated by cerebellar control of motor cortical activity, relayed through the cerebellar-thalamo-cortical (CTC system. Nonetheless, the way cerebellar information is integrated with motor cortical commands and affects their temporal properties remains unclear. To address this issue, we activated the CTC system in primates and found that it efficiently recruits motor cortical cells; however, the cortical response was dominated by prolonged inhibition that imposed a directional activation across the motor cortex. During task performance, cortical cells that integrated CTC information fired synchronous bursts at movement onset. These cells expressed a stronger correlation with reaction time than non-CTC cells. Thus, the excitation-inhibition interplay triggered by the CTC system facilitates transient recruitment of a cortical subnetwork at movement onset. The CTC system may shape neural firing to produce the required profile to initiate movements and thus plays a pivotal role in timing motor actions. : Nashef et al. identified a motor cortical subnetwork recruited by cerebellar volley that was transiently synchronized at movement onset. Cerebellar control of cortical firing was dominated by inhibition that shaped task-related firing of neurons and may dictate motor timing. Keywords: motor control, primates, cerebellar-thalamo-cortical, synchrony, noise correlation, reaction time

  4. Sensory cortical re-mapping following upper-limb amputation and subsequent targeted reinnervation: A case report

    Directory of Open Access Journals (Sweden)

    Jun Yao

    2015-01-01

    Full Text Available This case study demonstrates the change of sensory cortical representations of the residual parts of the arm in an individual who underwent a trans-humeral amputation and subsequent targeted reinnervation (TR. As a relatively new surgical technique, TR restores a direct neural connection from amputated sensorimotor nerves to specific target muscles. This method has been successfully applied to upper-limb and lower-limb amputees, and has shown effectiveness in regaining control signals via the newly re-innervated muscles. Correspondingly, recent study results have shown that motor representations for the missing limb move closer to their original locations following TR. Besides regaining motor control signals, TR also restores the sensation in the re-innervated skin areas. We therefore hypothesize that TR causes analogous cortical sensory remapping that may return closer to their original locations. In order to test this hypothesis, cortical activity in response to sensory-level electrical stimulation in different parts of the arm was studied longitudinally in one amputated individual before and up to 2 years after TR. Our results showed that 1 before TR, the cortical response to sensory electrical stimulation in the residual limb showed a diffuse bilateral pattern without a clear focus in either the time or spatial domain; and 2 2 years after TR, the sensory map of the reinnervated median nerve reorganized, showing predominant activity over the contralateral S1 hand area as well as moderate activity over the ipsilateral S1. Therefore, this work provides new evidence for long-term sensory cortical plasticity in the human brain after TR.

  5. Sensory cortical re-mapping following upper-limb amputation and subsequent targeted reinnervation: A case report.

    Science.gov (United States)

    Yao, Jun; Chen, Albert; Kuiken, Todd; Carmona, Carolina; Dewald, Julius

    2015-01-01

    This case study demonstrates the change of sensory cortical representations of the residual parts of the arm in an individual who underwent a trans-humeral amputation and subsequent targeted reinnervation (TR). As a relatively new surgical technique, TR restores a direct neural connection from amputated sensorimotor nerves to specific target muscles. This method has been successfully applied to upper-limb and lower-limb amputees, and has shown effectiveness in regaining control signals via the newly re-innervated muscles. Correspondingly, recent study results have shown that motor representations for the missing limb move closer to their original locations following TR. Besides regaining motor control signals, TR also restores the sensation in the re-innervated skin areas. We therefore hypothesize that TR causes analogous cortical sensory remapping that may return closer to their original locations. In order to test this hypothesis, cortical activity in response to sensory-level electrical stimulation in different parts of the arm was studied longitudinally in one amputated individual before and up to 2 years after TR. Our results showed that 1) before TR, the cortical response to sensory electrical stimulation in the residual limb showed a diffuse bilateral pattern without a clear focus in either the time or spatial domain; and 2) 2 years after TR, the sensory map of the reinnervated median nerve reorganized, showing predominant activity over the contralateral S1 hand area as well as moderate activity over the ipsilateral S1. Therefore, this work provides new evidence for long-term sensory cortical plasticity in the human brain after TR.

  6. Cortical basis of communication: local computation, coordination, attention.

    Science.gov (United States)

    Alexandre, Frederic

    2009-03-01

    Human communication emerges from cortical processing, known to be implemented on a regular repetitive neuronal substratum. The supposed genericity of cortical processing has elicited a series of modeling works in computational neuroscience that underline the information flows driven by the cortical circuitry. In the minimalist framework underlying the current theories for the embodiment of cognition, such a generic cortical processing is exploited for the coordination of poles of representation, as is reported in this paper for the case of visual attention. Interestingly, this case emphasizes how abstract internal referents are built to conform to memory requirements. This paper proposes that these referents are the basis for communication in humans, which is firstly a coordination and an attentional procedure with regard to their congeners.

  7. Basal Forebrain Gating by Somatostatin Neurons Drives Prefrontal Cortical Activity.

    Science.gov (United States)

    Espinosa, Nelson; Alonso, Alejandra; Morales, Cristian; Espinosa, Pedro; Chávez, Andrés E; Fuentealba, Pablo

    2017-11-17

    The basal forebrain provides modulatory input to the cortex regulating brain states and cognitive processing. Somatostatin-expressing neurons constitute a heterogeneous GABAergic population known to functionally inhibit basal forebrain cortically projecting cells thus favoring sleep and cortical synchronization. However, it remains unclear if somatostatin cells can regulate population activity patterns in the basal forebrain and modulate cortical dynamics. Here, we demonstrate that somatostatin neurons regulate the corticopetal synaptic output of the basal forebrain impinging on cortical activity and behavior. Optogenetic inactivation of somatostatin neurons in vivo rapidly modified neural activity in the basal forebrain, with the consequent enhancement and desynchronization of activity in the prefrontal cortex, reflected in both neuronal spiking and network oscillations. Cortical activation was partially dependent on cholinergic transmission, suppressing slow waves and potentiating gamma oscillations. In addition, recruitment dynamics was cell type-specific, with interneurons showing similar temporal profiles, but stronger responses than pyramidal cells. Finally, optogenetic stimulation of quiescent animals during resting periods prompted locomotor activity, suggesting generalized cortical activation and increased arousal. Altogether, we provide physiological and behavioral evidence indicating that somatostatin neurons are pivotal in gating the synaptic output of the basal forebrain, thus indirectly controlling cortical operations via both cholinergic and non-cholinergic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Influences of brain development and ageing on cortical interactive networks.

    Science.gov (United States)

    Zhu, Chengyu; Guo, Xiaoli; Jin, Zheng; Sun, Junfeng; Qiu, Yihong; Zhu, Yisheng; Tong, Shanbao

    2011-02-01

    To study the effect of brain development and ageing on the pattern of cortical interactive networks. By causality analysis of multichannel electroencephalograph (EEG) with partial directed coherence (PDC), we investigated the different neural networks involved in the whole cortex as well as the anterior and posterior areas in three age groups, i.e., children (0-10 years), mid-aged adults (26-38 years) and the elderly (56-80 years). By comparing the cortical interactive networks in different age groups, the following findings were concluded: (1) the cortical interactive network in the right hemisphere develops earlier than its left counterpart in the development stage; (2) the cortical interactive network of anterior cortex, especially at C3 and F3, is demonstrated to undergo far more extensive changes, compared with the posterior area during brain development and ageing; (3) the asymmetry of the cortical interactive networks declines during ageing with more loss of connectivity in the left frontal and central areas. The age-related variation of cortical interactive networks from resting EEG provides new insights into brain development and ageing. Our findings demonstrated that the PDC analysis of EEG is a powerful approach for characterizing the cortical functional connectivity during brain development and ageing. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  9. The neural basis of human social values: evidence from functional MRI.

    Science.gov (United States)

    Zahn, Roland; Moll, Jorge; Paiva, Mirella; Garrido, Griselda; Krueger, Frank; Huey, Edward D; Grafman, Jordan

    2009-02-01

    Social values are composed of social concepts (e.g., "generosity") and context-dependent moral sentiments (e.g., "pride"). The neural basis of this intricate cognitive architecture has not been investigated thus far. Here, we used functional magnetic resonance imaging while subjects imagined their own actions toward another person (self-agency) which either conformed or were counter to a social value and were associated with pride or guilt, respectively. Imagined actions of another person toward the subjects (other-agency) in accordance with or counter to a value were associated with gratitude or indignation/anger. As hypothesized, superior anterior temporal lobe (aTL) activity increased with conceptual detail in all conditions. During self-agency, activity in the anterior ventromedial prefrontal cortex correlated with pride and guilt, whereas activity in the subgenual cingulate solely correlated with guilt. In contrast, indignation/anger activated lateral orbitofrontal-insular cortices. Pride and gratitude additionally evoked mesolimbic and basal forebrain activations. Our results demonstrate that social values emerge from coactivation of stable abstract social conceptual representations in the superior aTL and context-dependent moral sentiments encoded in fronto-mesolimbic regions. This neural architecture may provide the basis of our ability to communicate about the meaning of social values across cultural contexts without limiting our flexibility to adapt their emotional interpretation.

  10. 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.

  11. Human brain basis of musical rhythm perception: common and distinct neural substrates for meter, tempo, and pattern.

    Science.gov (United States)

    Thaut, Michael H; Trimarchi, Pietro Davide; Parsons, Lawrence M

    2014-06-17

    Rhythm as the time structure of music is composed of distinct temporal components such as pattern, meter, and tempo. Each feature requires different computational processes: meter involves representing repeating cycles of strong and weak beats; pattern involves representing intervals at each local time point which vary in length across segments and are linked hierarchically; and tempo requires representing frequency rates of underlying pulse structures. We explored whether distinct rhythmic elements engage different neural mechanisms by recording brain activity of adult musicians and non-musicians with positron emission tomography (PET) as they made covert same-different discriminations of (a) pairs of rhythmic, monotonic tone sequences representing changes in pattern, tempo, and meter, and (b) pairs of isochronous melodies. Common to pattern, meter, and tempo tasks were focal activities in right, or bilateral, areas of frontal, cingulate, parietal, prefrontal, temporal, and cerebellar cortices. Meter processing alone activated areas in right prefrontal and inferior frontal cortex associated with more cognitive and abstract representations. Pattern processing alone recruited right cortical areas involved in different kinds of auditory processing. Tempo processing alone engaged mechanisms subserving somatosensory and premotor information (e.g., posterior insula, postcentral gyrus). Melody produced activity different from the rhythm conditions (e.g., right anterior insula and various cerebellar areas). These exploratory findings suggest the outlines of some distinct neural components underlying the components of rhythmic structure.

  12. Brain response to a humanoid robot in areas implicated in the perception of human emotional gestures.

    Directory of Open Access Journals (Sweden)

    Thierry Chaminade

    2010-07-01

    Full Text Available The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents.Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted.Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca's area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance.Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions.Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions.

  13. Brain response to a humanoid robot in areas implicated in the perception of human emotional gestures.

    Science.gov (United States)

    Chaminade, Thierry; Zecca, Massimiliano; Blakemore, Sarah-Jayne; Takanishi, Atsuo; Frith, Chris D; Micera, Silvestro; Dario, Paolo; Rizzolatti, Giacomo; Gallese, Vittorio; Umiltà, Maria Alessandra

    2010-07-21

    The humanoid robot WE4-RII was designed to express human emotions in order to improve human-robot interaction. We can read the emotions depicted in its gestures, yet might utilize different neural processes than those used for reading the emotions in human agents. Here, fMRI was used to assess how brain areas activated by the perception of human basic emotions (facial expression of Anger, Joy, Disgust) and silent speech respond to a humanoid robot impersonating the same emotions, while participants were instructed to attend either to the emotion or to the motion depicted. Increased responses to robot compared to human stimuli in the occipital and posterior temporal cortices suggest additional visual processing when perceiving a mechanical anthropomorphic agent. In contrast, activity in cortical areas endowed with mirror properties, like left Broca's area for the perception of speech, and in the processing of emotions like the left anterior insula for the perception of disgust and the orbitofrontal cortex for the perception of anger, is reduced for robot stimuli, suggesting lesser resonance with the mechanical agent. Finally, instructions to explicitly attend to the emotion significantly increased response to robot, but not human facial expressions in the anterior part of the left inferior frontal gyrus, a neural marker of motor resonance. Motor resonance towards a humanoid robot, but not a human, display of facial emotion is increased when attention is directed towards judging emotions. Artificial agents can be used to assess how factors like anthropomorphism affect neural response to the perception of human actions.

  14. The role of fluid intelligence and learning in analogical reasoning: How to become neurally efficient?

    Science.gov (United States)

    Dix, Annika; Wartenburger, Isabell; van der Meer, Elke

    2016-10-01

    This study on analogical reasoning evaluates the impact of fluid intelligence on adaptive changes in neural efficiency over the course of an experiment and specifies the underlying cognitive processes. Grade 10 students (N=80) solved unfamiliar geometric analogy tasks of varying difficulty. Neural efficiency was measured by the event-related desynchronization (ERD) in the alpha band, an indicator of cortical activity. Neural efficiency was defined as a low amount of cortical activity accompanying high performance during problem-solving. Students solved the tasks faster and more accurately the higher their FI was. Moreover, while high FI led to greater cortical activity in the first half of the experiment, high FI was associated with a neurally more efficient processing (i.e., better performance but same amount of cortical activity) in the second half of the experiment. Performance in difficult tasks improved over the course of the experiment for all students while neural efficiency increased for students with higher but decreased for students with lower fluid intelligence. Based on analyses of the alpha sub-bands, we argue that high fluid intelligence was associated with a stronger investment of attentional resource in the integration of information and the encoding of relations in this unfamiliar task in the first half of the experiment (lower-2 alpha band). Students with lower fluid intelligence seem to adapt their applied strategies over the course of the experiment (i.e., focusing on task-relevant information; lower-1 alpha band). Thus, the initially lower cortical activity and its increase in students with lower fluid intelligence might reflect the overcoming of mental overload that was present in the first half of the experiment. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Characterization of human neural differentiation from pluripotent stem cells using proteomics/PTMomics

    DEFF Research Database (Denmark)

    Braga, Marcella Nunes de Melo; Meyer, Morten; Zeng, Xianmin

    2015-01-01

    Stem cells are unspecialized cells capable of self-renewal and to differentiate into the large variety of cells in the body. The possibility to differentiate these cells into neural precursors and neural cells in vitro provides the opportunity to study neural development, nerve cell biology, neur...... differentiation from pluripotent stem cells. Moreover, some of the challenges in stem cell biology, differentiation, and proteomics/PTMomics that are not exclusive to neural development will be discussed.......Stem cells are unspecialized cells capable of self-renewal and to differentiate into the large variety of cells in the body. The possibility to differentiate these cells into neural precursors and neural cells in vitro provides the opportunity to study neural development, nerve cell biology...... the understanding of molecular processes in cells. Substantial advances in PTM enrichment methods and mass spectrometry has allowed the characterization of a subset of PTMs in large-scale studies. This review focuses on the current state-of-the-art of proteomic, as well as PTMomic studies related to human neural...

  16. Neural networks of human nature and nurture

    Directory of Open Access Journals (Sweden)

    Daniel S. Levine

    2009-11-01

    Full Text Available Neural network methods have facilitated the unification of several unfortunate splits in psychology, including nature versus nurture. We review the contributions of this methodology and then discuss tentative network theories of caring behavior, of uncaring behavior, and of how the frontal lobes are involved in the choices between them. The implications of our theory are optimistic about the prospects of society to encourage the human potential for caring.

  17. Heparan Sulfate Proteoglycans as Drivers of Neural Progenitors Derived From Human Mesenchymal Stem Cells.

    Science.gov (United States)

    Okolicsanyi, Rachel K; Oikari, Lotta E; Yu, Chieh; Griffiths, Lyn R; Haupt, Larisa M

    2018-01-01

    Background: Due to their relative ease of isolation and their high ex vivo and in vitro expansive potential, human mesenchymal stem cells (hMSCs) are an attractive candidate for therapeutic applications in the treatment of brain injury and neurological diseases. Heparan sulfate proteoglycans (HSPGs) are a family of ubiquitous proteins involved in a number of vital cellular processes including proliferation and stem cell lineage differentiation. Methods: Following the determination that hMSCs maintain neural potential throughout extended in vitro expansion, we examined the role of HSPGs in mediating the neural potential of hMSCs. hMSCs cultured in basal conditions (undifferentiated monolayer cultures) were found to co-express neural markers and HSPGs throughout expansion with modulation of the in vitro niche through the addition of exogenous HS influencing cellular HSPG and neural marker expression. Results: Conversion of hMSCs into hMSC Induced Neurospheres (hMSC IN) identified distinctly localized HSPG staining within the spheres along with altered gene expression of HSPG core protein and biosynthetic enzymes when compared to undifferentiated hMSCs. Conclusion: Comparison of markers of pluripotency, neural self-renewal and neural lineage specification between hMSC IN, hMSC and human neural stem cell (hNSC H9) cultures suggest that in vitro generated hMSC IN may represent an intermediary neurogenic cell type, similar to a common neural progenitor cell. In addition, this data demonstrates HSPGs and their biosynthesis machinery, are associated with hMSC IN formation. The identification of specific HSPGs driving hMSC lineage-specification will likely provide new markers to allow better use of hMSCs in therapeutic applications and improve our understanding of human neurogenesis.

  18. Dynamic decomposition of spatiotemporal neural signals.

    Directory of Open Access Journals (Sweden)

    Luca Ambrogioni

    2017-05-01

    Full Text Available Neural signals are characterized by rich temporal and spatiotemporal dynamics that reflect the organization of cortical networks. Theoretical research has shown how neural networks can operate at different dynamic ranges that correspond to specific types of information processing. Here we present a data analysis framework that uses a linearized model of these dynamic states in order to decompose the measured neural signal into a series of components that capture both rhythmic and non-rhythmic neural activity. The method is based on stochastic differential equations and Gaussian process regression. Through computer simulations and analysis of magnetoencephalographic data, we demonstrate the efficacy of the method in identifying meaningful modulations of oscillatory signals corrupted by structured temporal and spatiotemporal noise. These results suggest that the method is particularly suitable for the analysis and interpretation of complex temporal and spatiotemporal neural signals.

  19. Edentulation alters material properties of cortical bone in the human craniofacial skeleton: functional implications for craniofacial structure in primate evolution

    Science.gov (United States)

    Dechow, Paul C.; Wang, Qian; Peterson, Jill

    2011-01-01

    Skeletal adaptations to reduced function are an important source of skeletal variation and may be indicative of environmental pressures that lead to evolutionary changes. Humans serve as a model animal to investigate the effects of loss of craniofacial function through edentulation. In the human maxilla, it is known that edentulation leads to significant changes in skeletal structure such as residual ridge resorption and loss of cortical thickness. However, little is known about changes in bone tissue structure and material properties, which are also important for understanding skeletal mechanics but are often ignored. The aims of this study were to determine cortical material properties in edentulous crania and to evaluate differences with dentate crania and thus examine the effects of loss of function on craniofacial structure. Cortical bone samples from fifteen edentulous human skulls were measured for thickness and density. Elastic properties and directions of maximum stiffness were determined by using ultrasonic techniques. These data were compared to those from dentate crania reported in a previous investigation. Cortical bone from all regions of the facial skeleton of edentulous individuals is thinner than in dentate skulls. Elastic and shear moduli, and density are similar or greater in the zygoma and cranial vault of edentulous individuals, while these properties are less in the maxilla. Most cortical bone, especially in edentulous maxillae, has reduced directional orientation. The loss of significant occlusal loads following edentulation may contribute to the change in material properties and the loss of orientation over time during the normal process of bone remodeling. These results suggest that area-specific cortical microstructural changes accompany bone resorption following edentulation. They also suggest that functional forces are important for maintaining bone mass throughout the craniofacial skeleton, even in areas such as the browridges, which

  20. Major Thought Restructuring: The Roles of Different Prefrontal Cortical Regions.

    Science.gov (United States)

    Seyed-Allaei, Shima; Avanaki, Zahra Nasiri; Bahrami, Bahador; Shallice, Tim

    2017-07-01

    An important question for understanding the neural basis of problem solving is whether the regions of human prefrontal cortices play qualitatively different roles in the major cognitive restructuring required to solve difficult problems. However, investigating this question using neuroimaging faces a major dilemma: either the problems do not require major cognitive restructuring, or if they do, the restructuring typically happens once, rendering repeated measurements of the critical mental process impossible. To circumvent these problems, young adult participants were challenged with a one-dimensional Subtraction (or Nim) problem [Bouton, C. L. Nim, a game with a complete mathematical theory. The Annals of Mathematics, 3, 35-39, 1901] that can be tackled using two possible strategies. One, often used initially, is effortful, slow, and error-prone, whereas the abstract solution, once achieved, is easier, quicker, and more accurate. Behaviorally, success was strongly correlated with sex. Using voxel-based morphometry analysis controlling for sex, we found that participants who found the more abstract strategy (i.e., Solvers) had more gray matter volume in the anterior medial, ventrolateral prefrontal, and parietal cortices compared with those who never switched from the initial effortful strategy (i.e., Explorers). Removing the sex covariate showed higher gray matter volume in Solvers (vs. Explorers) in the right ventrolateral prefrontal and left parietal cortex.

  1. The use of artificial neural network to evaluate the effects of human ...

    African Journals Online (AJOL)

    The use of artificial neural network to evaluate the effects of human and physiographic factors on forest stock volume. ... stock volume and human factors in certain topography conditions and provides useful information for the acceptable amount of standing inventory using the present human population in future experiment.

  2. Familiarity Detection is an Intrinsic Property of Cortical Microcircuits with Bidirectional Synaptic Plasticity.

    Science.gov (United States)

    Zhang, Xiaoyu; Ju, Han; Penney, Trevor B; VanDongen, Antonius M J

    2017-01-01

    Humans instantly recognize a previously seen face as "familiar." To deepen our understanding of familiarity-novelty detection, we simulated biologically plausible neural network models of generic cortical microcircuits consisting of spiking neurons with random recurrent synaptic connections. NMDA receptor (NMDAR)-dependent synaptic plasticity was implemented to allow for unsupervised learning and bidirectional modifications. Network spiking activity evoked by sensory inputs consisting of face images altered synaptic efficacy, which resulted in the network responding more strongly to a previously seen face than a novel face. Network size determined how many faces could be accurately recognized as familiar. When the simulated model became sufficiently complex in structure, multiple familiarity traces could be retained in the same network by forming partially-overlapping subnetworks that differ slightly from each other, thereby resulting in a high storage capacity. Fisher's discriminant analysis was applied to identify critical neurons whose spiking activity predicted familiar input patterns. Intriguingly, as sensory exposure was prolonged, the selected critical neurons tended to appear at deeper layers of the network model, suggesting recruitment of additional circuits in the network for incremental information storage. We conclude that generic cortical microcircuits with bidirectional synaptic plasticity have an intrinsic ability to detect familiar inputs. This ability does not require a specialized wiring diagram or supervision and can therefore be expected to emerge naturally in developing cortical circuits.

  3. The psychosis-like effects of Δ(9)-tetrahydrocannabinol are associated with increased cortical noise in healthy humans.

    Science.gov (United States)

    Cortes-Briones, Jose A; Cahill, John D; Skosnik, Patrick D; Mathalon, Daniel H; Williams, Ashley; Sewell, R Andrew; Roach, Brian J; Ford, Judith M; Ranganathan, Mohini; D'Souza, Deepak Cyril

    2015-12-01

    Drugs that induce psychosis may do so by increasing the level of task-irrelevant random neural activity or neural noise. Increased levels of neural noise have been demonstrated in psychotic disorders. We tested the hypothesis that neural noise could also be involved in the psychotomimetic effects of delta-9-tetrahydrocannabinol (Δ(9)-THC), the principal active constituent of cannabis. Neural noise was indexed by measuring the level of randomness in the electroencephalogram during the prestimulus baseline period of an oddball task using Lempel-Ziv complexity, a nonlinear measure of signal randomness. The acute, dose-related effects of Δ(9)-THC on Lempel-Ziv complexity and signal power were studied in humans (n = 24) who completed 3 test days during which they received intravenous Δ(9)-THC (placebo, .015 and .03 mg/kg) in a double-blind, randomized, crossover, and counterbalanced design. Δ(9)-THC increased neural noise in a dose-related manner. Furthermore, there was a strong positive relationship between neural noise and the psychosis-like positive and disorganization symptoms induced by Δ(9)-THC, which was independent of total signal power. Instead, there was no relationship between noise and negative-like symptoms. In addition, Δ(9)-THC reduced total signal power during both active drug conditions compared with placebo, but no relationship was detected between signal power and psychosis-like symptoms. At doses that produced psychosis-like effects, Δ(9)-THC increased neural noise in humans in a dose-dependent manner. Furthermore, increases in neural noise were related with increases in Δ(9)-THC-induced psychosis-like symptoms but not negative-like symptoms. These findings suggest that increases in neural noise may contribute to the psychotomimetic effects of Δ(9)-THC. Published by Elsevier Inc.

  4. Competing sound sources reveal spatial effects in cortical processing.

    Directory of Open Access Journals (Sweden)

    Ross K Maddox

    Full Text Available Why is spatial tuning in auditory cortex weak, even though location is important to object recognition in natural settings? This question continues to vex neuroscientists focused on linking physiological results to auditory perception. Here we show that the spatial locations of simultaneous, competing sound sources dramatically influence how well neural spike trains recorded from the zebra finch field L (an analog of mammalian primary auditory cortex encode source identity. We find that the location of a birdsong played in quiet has little effect on the fidelity of the neural encoding of the song. However, when the song is presented along with a masker, spatial effects are pronounced. For each spatial configuration, a subset of neurons encodes song identity more robustly than others. As a result, competing sources from different locations dominate responses of different neural subpopulations, helping to separate neural responses into independent representations. These results help elucidate how cortical processing exploits spatial information to provide a substrate for selective spatial auditory attention.

  5. Visual Dysfunction in Posterior Cortical Atrophy

    Science.gov (United States)

    Maia da Silva, Mari N.; Millington, Rebecca S.; Bridge, Holly; James-Galton, Merle; Plant, Gordon T.

    2017-01-01

    Posterior cortical atrophy (PCA) is a syndromic diagnosis. It is characterized by progressive impairment of higher (cortical) visual function with imaging evidence of degeneration affecting the occipital, parietal, and posterior temporal lobes bilaterally. Most cases will prove to have Alzheimer pathology. The aim of this review is to summarize the development of the concept of this disorder since it was first introduced. A critical discussion of the evolving diagnostic criteria is presented and the differential diagnosis with regard to the underlying pathology is reviewed. Emphasis is given to the visual dysfunction that defines the disorder, and the classical deficits, such as simultanagnosia and visual agnosia, as well as the more recently recognized visual field defects, are reviewed, along with the evidence on their neural correlates. The latest developments on the imaging of PCA are summarized, with special attention to its role on the differential diagnosis with related conditions. PMID:28861031

  6. Visual Dysfunction in Posterior Cortical Atrophy

    Directory of Open Access Journals (Sweden)

    Mari N. Maia da Silva

    2017-08-01

    Full Text Available Posterior cortical atrophy (PCA is a syndromic diagnosis. It is characterized by progressive impairment of higher (cortical visual function with imaging evidence of degeneration affecting the occipital, parietal, and posterior temporal lobes bilaterally. Most cases will prove to have Alzheimer pathology. The aim of this review is to summarize the development of the concept of this disorder since it was first introduced. A critical discussion of the evolving diagnostic criteria is presented and the differential diagnosis with regard to the underlying pathology is reviewed. Emphasis is given to the visual dysfunction that defines the disorder, and the classical deficits, such as simultanagnosia and visual agnosia, as well as the more recently recognized visual field defects, are reviewed, along with the evidence on their neural correlates. The latest developments on the imaging of PCA are summarized, with special attention to its role on the differential diagnosis with related conditions.

  7. Membrane potential dynamics of populations of cortical neurons during auditory streaming

    Science.gov (United States)

    Farley, Brandon J.

    2015-01-01

    How a mixture of acoustic sources is perceptually organized into discrete auditory objects remains unclear. One current hypothesis postulates that perceptual segregation of different sources is related to the spatiotemporal separation of cortical responses induced by each acoustic source or stream. In the present study, the dynamics of subthreshold membrane potential activity were measured across the entire tonotopic axis of the rodent primary auditory cortex during the auditory streaming paradigm using voltage-sensitive dye imaging. Consistent with the proposed hypothesis, we observed enhanced spatiotemporal segregation of cortical responses to alternating tone sequences as their frequency separation or presentation rate was increased, both manipulations known to promote stream segregation. However, across most streaming paradigm conditions tested, a substantial cortical region maintaining a response to both tones coexisted with more peripheral cortical regions responding more selectively to one of them. We propose that these coexisting subthreshold representation types could provide neural substrates to support the flexible switching between the integrated and segregated streaming percepts. PMID:26269558

  8. Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus.

    Science.gov (United States)

    Khodagholy, Dion; Gelinas, Jennifer N; Buzsáki, György

    2017-10-20

    Consolidation of declarative memories requires hippocampal-neocortical communication. Although experimental evidence supports the role of sharp-wave ripples in transferring hippocampal information to the neocortex, the exact cortical destinations and the physiological mechanisms of such transfer are not known. We used a conducting polymer-based conformable microelectrode array (NeuroGrid) to record local field potentials and neural spiking across the dorsal cortical surface of the rat brain, combined with silicon probe recordings in the hippocampus, to identify candidate physiological patterns. Parietal, midline, and prefrontal, but not primary cortical areas, displayed localized ripple (100 to 150 hertz) oscillations during sleep, concurrent with hippocampal ripples. Coupling between hippocampal and neocortical ripples was strengthened during sleep following learning. These findings suggest that ripple-ripple coupling supports hippocampal-association cortical transfer of memory traces. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  9. Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons.

    Science.gov (United States)

    Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew Cn; Swindale, Nicholas V; Murphy, Timothy H

    2017-02-04

    Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps.

  10. Cortical plasticity induced by spike-triggered microstimulation in primate somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Weiguo Song

    Full Text Available Electrical stimulation of the nervous system for therapeutic purposes, such as deep brain stimulation in the treatment of Parkinson's disease, has been used for decades. Recently, increased attention has focused on using microstimulation to restore functions as diverse as somatosensation and memory. However, how microstimulation changes the neural substrate is still not fully understood. Microstimulation may cause cortical changes that could either compete with or complement natural neural processes, and could result in neuroplastic changes rendering the region dysfunctional or even epileptic. As part of our efforts to produce neuroprosthetic devices and to further study the effects of microstimulation on the cortex, we stimulated and recorded from microelectrode arrays in the hand area of the primary somatosensory cortex (area 1 in two awake macaque monkeys. We applied a simple neuroprosthetic microstimulation protocol to a pair of electrodes in the area 1 array, using either random pulses or pulses time-locked to the recorded spiking activity of a reference neuron. This setup was replicated using a computer model of the thalamocortical system, which consisted of 1980 spiking neurons distributed among six cortical layers and two thalamic nuclei. Experimentally, we found that spike-triggered microstimulation induced cortical plasticity, as shown by increased unit-pair mutual information, while random microstimulation did not. In addition, there was an increased response to touch following spike-triggered microstimulation, along with decreased neural variability. The computer model successfully reproduced both qualitative and quantitative aspects of the experimental findings. The physiological findings of this study suggest that even simple microstimulation protocols can be used to increase somatosensory information flow.

  11. Probabilistic inference under time pressure leads to a cortical-to-subcortical shift in decision evidence integration.

    Science.gov (United States)

    Oh-Descher, Hanna; Beck, Jeffrey M; Ferrari, Silvia; Sommer, Marc A; Egner, Tobias

    2017-11-15

    Real-life decision-making often involves combining multiple probabilistic sources of information under finite time and cognitive resources. To mitigate these pressures, people "satisfice", foregoing a full evaluation of all available evidence to focus on a subset of cues that allow for fast and "good-enough" decisions. Although this form of decision-making likely mediates many of our everyday choices, very little is known about the way in which the neural encoding of cue information changes when we satisfice under time pressure. Here, we combined human functional magnetic resonance imaging (fMRI) with a probabilistic classification task to characterize neural substrates of multi-cue decision-making under low (1500 ms) and high (500 ms) time pressure. Using variational Bayesian inference, we analyzed participants' choices to track and quantify cue usage under each experimental condition, which was then applied to model the fMRI data. Under low time pressure, participants performed near-optimally, appropriately integrating all available cues to guide choices. Both cortical (prefrontal and parietal cortex) and subcortical (hippocampal and striatal) regions encoded individual cue weights, and activity linearly tracked trial-by-trial variations in the amount of evidence and decision uncertainty. Under increased time pressure, participants adaptively shifted to using a satisficing strategy by discounting the least informative cue in their decision process. This strategic change in decision-making was associated with an increased involvement of the dopaminergic midbrain, striatum, thalamus, and cerebellum in representing and integrating cue values. We conclude that satisficing the probabilistic inference process under time pressure leads to a cortical-to-subcortical shift in the neural drivers of decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The spiritual brain: selective cortical lesions modulate human self-transcendence.

    Science.gov (United States)

    Urgesi, Cosimo; Aglioti, Salvatore M; Skrap, Miran; Fabbro, Franco

    2010-02-11

    The predisposition of human beings toward spiritual feeling, thinking, and behaviors is measured by a supposedly stable personality trait called self-transcendence. Although a few neuroimaging studies suggest that neural activation of a large fronto-parieto-temporal network may underpin a variety of spiritual experiences, information on the causative link between such a network and spirituality is lacking. Combining pre- and post-neurosurgery personality assessment with advanced brain-lesion mapping techniques, we found that selective damage to left and right inferior posterior parietal regions induced a specific increase of self-transcendence. Therefore, modifications of neural activity in temporoparietal areas may induce unusually fast modulations of a stable personality trait related to transcendental self-referential awareness. These results hint at the active, crucial role of left and right parietal systems in determining self-transcendence and cast new light on the neurobiological bases of altered spiritual and religious attitudes and behaviors in neurological and mental disorders. Copyright 2010 Elsevier Inc. All rights reserved.

  13. Neural systems for preparatory control of imitation.

    Science.gov (United States)

    Cross, Katy A; Iacoboni, Marco

    2014-01-01

    Humans have an automatic tendency to imitate others. Previous studies on how we control these tendencies have focused on reactive mechanisms, where inhibition of imitation is implemented after seeing an action. This work suggests that reactive control of imitation draws on at least partially specialized mechanisms. Here, we examine preparatory imitation control, where advance information allows control processes to be employed before an action is observed. Drawing on dual route models from the spatial compatibility literature, we compare control processes using biological and non-biological stimuli to determine whether preparatory imitation control recruits specialized neural systems that are similar to those observed in reactive imitation control. Results indicate that preparatory control involves anterior prefrontal, dorsolateral prefrontal, posterior parietal and early visual cortices regardless of whether automatic responses are evoked by biological (imitative) or non-biological stimuli. These results indicate both that preparatory control of imitation uses general mechanisms, and that preparatory control of imitation draws on different neural systems from reactive imitation control. Based on the regions involved, we hypothesize that preparatory control is implemented through top-down attentional biasing of visual processing.

  14. Generation and properties of a new human ventral mesencephalic neural stem cell line

    DEFF Research Database (Denmark)

    Villa, Ana; Liste, Isabel; Courtois, Elise T

    2009-01-01

    . Here we report the generation of a new stable cell line of human neural stem cells derived from ventral mesencephalon (hVM1) based on v-myc immortalization. The cells expressed neural stem cell and radial glia markers like nestin, vimentin and 3CB2 under proliferation conditions. After withdrawal......Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to cell therapy in neurodegenerative diseases like Parkinson's disease. Several epigenetic and genetic strategies have been tested for long-term maintenance and expansion of these cells in vitro...... derivatives may constitute good candidates for the study of development and physiology of human dopaminergic neurons in vitro, and to develop tools for Parkinson's disease cell replacement preclinical research and drug testing....

  15. A Chronically Implantable Bidirectional Neural Interface for Non-human Primates

    Directory of Open Access Journals (Sweden)

    Misako Komatsu

    2017-09-01

    Full Text Available Optogenetics has potential applications in the study of epilepsy and neuroprostheses, and for studies on neural circuit dynamics. However, to achieve translation to clinical usage, optogenetic interfaces that are capable of chronic stimulation and monitoring with minimal brain trauma are required. We aimed to develop a chronically implantable device for photostimulation of the brain of non-human primates. We used a micro-light-emitting diode (LED array with a flexible polyimide film. The array was combined with a whole-cortex electrocorticographic (ECoG electrode array for simultaneous photostimulation and recording. Channelrhodopsin-2 (ChR2 was virally transduced into the cerebral cortex of common marmosets, and then the device was epidurally implanted into their brains. We recorded the neural activity during photostimulation of the awake monkeys for 4 months. The neural responses gradually increased after the virus injection for ~8 weeks and remained constant for another 8 weeks. The micro-LED and ECoG arrays allowed semi-invasive simultaneous stimulation and recording during long-term implantation in the brains of non-human primates. The development of this device represents substantial progress in the field of optogenetic applications.

  16. Functional evolution of new and expanded attention networks in humans.

    Science.gov (United States)

    Patel, Gaurav H; Yang, Danica; Jamerson, Emery C; Snyder, Lawrence H; Corbetta, Maurizio; Ferrera, Vincent P

    2015-07-28

    Macaques are often used as a model system for invasive investigations of the neural substrates of cognition. However, 25 million years of evolution separate humans and macaques from their last common ancestor, and this has likely substantially impacted the function of the cortical networks underlying cognitive processes, such as attention. We examined the homology of frontoparietal networks underlying attention by comparing functional MRI data from macaques and humans performing the same visual search task. Although there are broad similarities, we found fundamental differences between the species. First, humans have more dorsal attention network areas than macaques, indicating that in the course of evolution the human attention system has expanded compared with macaques. Second, potentially homologous areas in the dorsal attention network have markedly different biases toward representing the contralateral hemifield, indicating that the underlying neural architecture of these areas may differ in the most basic of properties, such as receptive field distribution. Third, despite clear evidence of the temporoparietal junction node of the ventral attention network in humans as elicited by this visual search task, we did not find functional evidence of a temporoparietal junction in macaques. None of these differences were the result of differences in training, experimental power, or anatomical variability between the two species. The results of this study indicate that macaque data should be applied to human models of cognition cautiously, and demonstrate how evolution may shape cortical networks.

  17. Cortical plasticity as a mechanism for storing Bayesian priors in sensory perception.

    Science.gov (United States)

    Köver, Hania; Bao, Shaowen

    2010-05-05

    Human perception of ambiguous sensory signals is biased by prior experiences. It is not known how such prior information is encoded, retrieved and combined with sensory information by neurons. Previous authors have suggested dynamic encoding mechanisms for prior information, whereby top-down modulation of firing patterns on a trial-by-trial basis creates short-term representations of priors. Although such a mechanism may well account for perceptual bias arising in the short-term, it does not account for the often irreversible and robust changes in perception that result from long-term, developmental experience. Based on the finding that more frequently experienced stimuli gain greater representations in sensory cortices during development, we reasoned that prior information could be stored in the size of cortical sensory representations. For the case of auditory perception, we use a computational model to show that prior information about sound frequency distributions may be stored in the size of primary auditory cortex frequency representations, read-out by elevated baseline activity in all neurons and combined with sensory-evoked activity to generate a perception that conforms to Bayesian integration theory. Our results suggest an alternative neural mechanism for experience-induced long-term perceptual bias in the context of auditory perception. They make the testable prediction that the extent of such perceptual prior bias is modulated by both the degree of cortical reorganization and the magnitude of spontaneous activity in primary auditory cortex. Given that cortical over-representation of frequently experienced stimuli, as well as perceptual bias towards such stimuli is a common phenomenon across sensory modalities, our model may generalize to sensory perception, rather than being specific to auditory perception.

  18. Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.

    Science.gov (United States)

    Mardinly, A R; Spiegel, I; Patrizi, A; Centofante, E; Bazinet, J E; Tzeng, C P; Mandel-Brehm, C; Harmin, D A; Adesnik, H; Fagiolini, M; Greenberg, M E

    2016-03-17

    Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.

  19. Dendritic nonlinearities are tuned for efficient spike-based computations in cortical circuits.

    Science.gov (United States)

    Ujfalussy, Balázs B; Makara, Judit K; Branco, Tiago; Lengyel, Máté

    2015-12-24

    Cortical neurons integrate thousands of synaptic inputs in their dendrites in highly nonlinear ways. It is unknown how these dendritic nonlinearities in individual cells contribute to computations at the level of neural circuits. Here, we show that dendritic nonlinearities are critical for the efficient integration of synaptic inputs in circuits performing analog computations with spiking neurons. We developed a theory that formalizes how a neuron's dendritic nonlinearity that is optimal for integrating synaptic inputs depends on the statistics of its presynaptic activity patterns. Based on their in vivo preynaptic population statistics (firing rates, membrane potential fluctuations, and correlations due to ensemble dynamics), our theory accurately predicted the responses of two different types of cortical pyramidal cells to patterned stimulation by two-photon glutamate uncaging. These results reveal a new computational principle underlying dendritic integration in cortical neurons by suggesting a functional link between cellular and systems--level properties of cortical circuits.

  20. How Tough is Human Cortical Bone? In-Situ Measurements on Realistically Short Cracks

    Energy Technology Data Exchange (ETDEWEB)

    Ritchie, Robert O; Koester, K. J.; Ager III, J. W.; Ritchie, R.O.

    2008-05-10

    Bone is more difficult to break than to split. Although this is well known, and many studies exist on the behavior of long cracks in bone, there is a need for data on the orientation-dependent crack-growth resistance behavior of human cortical bone which accurately assesses its toughness at appropriate size-scales. Here we use in-situ mechanical testing in the scanning electron microscope and x-ray computed tomography to examine how physiologically-pertinent short (<600 mu m) cracks propagate in both the transverse and longitudinal orientations in cortical bone, using both crack-deflection/twist mechanics and nonlinear-elastic fracture mechanics to determine crack-resistance curves. We find that after only 500 mu m of cracking, the driving force for crack propagation was more than five times higher in the transverse (breaking) direction than in the longitudinal (splitting) direction due to major crack deflections/twists principally at cement sheathes. Indeed, our results show that the true transverse toughness of cortical bone is far higher than previously reported. However, the toughness in the longitudinal orientation, where cracks tend to follow the cement lines, is quite low at these small crack sizes; it is only when cracks become several millimeters in length that bridging mechanisms can develop leading to the (larger-crack) toughnesses generally quoted for bone.

  1. An overview of neural function and feedback control in human communication.

    Science.gov (United States)

    Hood, L J

    1998-01-01

    The speech and hearing mechanisms depend on accurate sensory information and intact feedback mechanisms to facilitate communication. This article provides a brief overview of some components of the nervous system important for human communication and some electrophysiological methods used to measure cortical function in humans. An overview of automatic control and feedback mechanisms in general and as they pertain to the speech motor system and control of the hearing periphery is also presented, along with a discussion of how the speech and auditory systems interact.

  2. Cortical drive to breathe in amyotrophic lateral sclerosis: a dyspnoea-worsening defence?

    Science.gov (United States)

    Georges, Marjolaine; Morawiec, Elise; Raux, Mathieu; Gonzalez-Bermejo, Jésus; Pradat, Pierre-François; Similowski, Thomas; Morélot-Panzini, Capucine

    2016-06-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing diaphragm weakness that can be partially compensated by inspiratory neck muscle recruitment. This disappears during sleep, which is compatible with a cortical contribution to the drive to breathe. We hypothesised that ALS patients with respiratory failure exhibit respiratory-related cortical activity, relieved by noninvasive ventilation (NIV) and related to dyspnoea.We studied 14 ALS patients with respiratory failure. Electroencephalographic recordings (EEGs) and electromyographic recordings of inspiratory neck muscles were performed during spontaneous breathing and NIV. Dyspnoea was evaluated using the Multidimensional Dyspnea Profile.Eight patients exhibited slow EEG negativities preceding inspiration (pre-inspiratory potentials) during spontaneous breathing. Pre-inspiratory potentials were attenuated during NIV (p=0.04). Patients without pre-inspiratory potentials presented more advanced forms of ALS and more severe respiratory impairment, but less severe dyspnoea. Patients with pre-inspiratory potentials had stronger inspiratory neck muscle activation and more severe dyspnoea during spontaneous breathing.ALS-related diaphragm weakness can engage cortical resources to augment the neural drive to breathe. This might reflect a compensatory mechanism, with the intensity of dyspnoea a negative consequence. Disease progression and the corresponding neural loss could abolish this phenomenon. A putative cognitive cost should be investigated. Copyright ©ERS 2016.

  3. A Mechanistic Link from GABA to Cortical Architecture and Perception.

    Science.gov (United States)

    Kolasinski, James; Logan, John P; Hinson, Emily L; Manners, Daniel; Divanbeighi Zand, Amir P; Makin, Tamar R; Emir, Uzay E; Stagg, Charlotte J

    2017-06-05

    Understanding both the organization of the human cortex and its relation to the performance of distinct functions is fundamental in neuroscience. The primary sensory cortices display topographic organization, whereby receptive fields follow a characteristic pattern, from tonotopy to retinotopy to somatotopy [1]. GABAergic signaling is vital to the maintenance of cortical receptive fields [2]; however, it is unclear how this fine-grain inhibition relates to measurable patterns of perception [3, 4]. Based on perceptual changes following perturbation of the GABAergic system, it is conceivable that the resting level of cortical GABAergic tone directly relates to the spatial specificity of activation in response to a given input [5-7]. The specificity of cortical activation can be considered in terms of cortical tuning: greater cortical tuning yields more localized recruitment of cortical territory in response to a given input. We applied a combination of fMRI, MR spectroscopy, and psychophysics to substantiate the link between the cortical neurochemical milieu, the tuning of cortical activity, and variability in perceptual acuity, using human somatosensory cortex as a model. We provide data that explain human perceptual acuity in terms of both the underlying cellular and metabolic processes. Specifically, higher concentrations of sensorimotor GABA are associated with more selective cortical tuning, which in turn is associated with enhanced perception. These results show anatomical and neurochemical specificity and are replicated in an independent cohort. The mechanistic link from neurochemistry to perception provides a vital step in understanding population variability in sensory behavior, informing metabolic therapeutic interventions to restore perceptual abilities clinically. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  4. Cortical and spinal excitability during and after lengthening contractions of the human plantar flexor muscles performed with maximal voluntary effort.

    Directory of Open Access Journals (Sweden)

    Daniel Hahn

    Full Text Available This study was designed to investigate the sites of potential specific modulations in the neural control of lengthening and subsequent isometric maximal voluntary contractions (MVCs versus purely isometric MVCs of the plantar flexor muscles, when there is enhanced torque during and following stretch. Ankle joint torque during maximum voluntary plantar flexion was measured by a dynamometer when subjects (n = 10 lay prone on a bench with the right ankle tightly strapped to a foot-plate. Neural control was analysed by comparing soleus motor responses to electrical nerve stimulation (M-wave, V-wave, electrical stimulation of the cervicomedullary junction (CMEP and transcranial magnetic stimulation of the motor cortex (MEP. Enhanced torque of 17 ± 8% and 9 ± 8% was found during and 2.5-3 s after lengthening MVCs, respectively. Cortical and spinal responsiveness was similar to that in isometric conditions during the lengthening MVCs, as shown by unchanged MEPs, CMEPs and V-waves, suggesting that the major voluntary motor pathways are not subject to substantial inhibition. Following the lengthening MVCs, enhanced torque was accompanied by larger MEPs (p ≤ 0.05 and a trend to greater V-waves (p ≤ 0.1. In combination with stable CMEPs, increased MEPs suggest an increase in cortical excitability, and enlarged V-waves indicate greater motoneuronal output or increased stretch reflex excitability. The new results illustrate that neuromotor pathways are altered after lengthening MVCs suggesting that the underlying mechanisms of the enhanced torque are not purely mechanical in nature.

  5. Infant joint attention, neural networks and social cognition.

    Science.gov (United States)

    Mundy, Peter; Jarrold, William

    2010-01-01

    Neural network models of attention can provide a unifying approach to the study of human cognitive and emotional development (Posner & Rothbart, 2007). In this paper we argue that a neural network approach to the infant development of joint attention can inform our understanding of the nature of human social learning, symbolic thought process and social cognition. At its most basic, joint attention involves the capacity to coordinate one's own visual attention with that of another person. We propose that joint attention development involves increments in the capacity to engage in simultaneous or parallel processing of information about one's own attention and the attention of other people. Infant practice with joint attention is both a consequence and an organizer of the development of a distributed and integrated brain network involving frontal and parietal cortical systems. This executive distributed network first serves to regulate the capacity of infants to respond to and direct the overt behavior of other people in order to share experience with others through the social coordination of visual attention. In this paper we describe this parallel and distributed neural network model of joint attention development and discuss two hypotheses that stem from this model. One is that activation of this distributed network during coordinated attention enhances the depth of information processing and encoding beginning in the first year of life. We also propose that with development, joint attention becomes internalized as the capacity to socially coordinate mental attention to internal representations. As this occurs the executive joint attention network makes vital contributions to the development of human symbolic thinking and social cognition. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Human cortical activity related to unilateral movements. A high resolution EEG study.

    Science.gov (United States)

    Urbano, A; Babiloni, C; Onorati, P; Babiloni, F

    1996-12-20

    In the present study a modern high resolution electroencephalography (EEG) technique was used to investigate the dynamic functional topography of human cortical activity related to simple unilateral internally triggered finger movements. The sensorimotor area (M1-S1) contralateral to the movement as well as the supplementary motor area (SMA) and to a lesser extent the ipsilateral M1-S1 were active during the preparation and execution of these movements. These findings suggest that both hemispheres may cooperate in both planning and production of simple unilateral volitional acts.

  7. Short-term synaptic plasticity and heterogeneity in neural systems

    Science.gov (United States)

    Mejias, J. F.; Kappen, H. J.; Longtin, A.; Torres, J. J.

    2013-01-01

    We review some recent results on neural dynamics and information processing which arise when considering several biophysical factors of interest, in particular, short-term synaptic plasticity and neural heterogeneity. The inclusion of short-term synaptic plasticity leads to enhanced long-term memory capacities, a higher robustness of memory to noise, and irregularity in the duration of the so-called up cortical states. On the other hand, considering some level of neural heterogeneity in neuron models allows neural systems to optimize information transmission in rate coding and temporal coding, two strategies commonly used by neurons to codify information in many brain areas. In all these studies, analytical approximations can be made to explain the underlying dynamics of these neural systems.

  8. In vitro characterization of a human neural progenitor cell coexpressing SSEA4 and CD133

    DEFF Research Database (Denmark)

    Barraud, Perrine; Stott, Simon; Møllgård, Kjeld

    2007-01-01

    The stage-specific embryonic antigen 4 (SSEA4) is commonly used as a cell surface marker to identify the pluripotent human embryonic stem (ES) cells. Immunohistochemistry on human embryonic central nervous system revealed that SSEA4 is detectable in the early neuroepithelium, and its expression....... Therefore, we propose that SSEA4 associated with CD133 can be used for both the positive selection and the enrichment of neural stem/progenitor cells from human embryonic forebrain....... decreases as development proceeds. Flow cytometry analysis of forebrain-derived cells demonstrated that the SSEA4-expressing cells are enriched in the neural stem/progenitor cell fraction (CD133(+)), but are rarely codetected with the neural stem cell (NSC) marker CD15. Using a sphere-forming assay, we...

  9. A Grey Wolf Optimizer for Modular Granular Neural Networks for Human Recognition

    Directory of Open Access Journals (Sweden)

    Daniela Sánchez

    2017-01-01

    Full Text Available A grey wolf optimizer for modular neural network (MNN with a granular approach is proposed. The proposed method performs optimal granulation of data and design of modular neural networks architectures to perform human recognition, and to prove its effectiveness benchmark databases of ear, iris, and face biometric measures are used to perform tests and comparisons against other works. The design of a modular granular neural network (MGNN consists in finding optimal parameters of its architecture; these parameters are the number of subgranules, percentage of data for the training phase, learning algorithm, goal error, number of hidden layers, and their number of neurons. Nowadays, there is a great variety of approaches and new techniques within the evolutionary computing area, and these approaches and techniques have emerged to help find optimal solutions to problems or models and bioinspired algorithms are part of this area. In this work a grey wolf optimizer is proposed for the design of modular granular neural networks, and the results are compared against a genetic algorithm and a firefly algorithm in order to know which of these techniques provides better results when applied to human recognition.

  10. Altered Regional Brain Cortical Thickness in Pediatric Obstructive Sleep Apnea

    Directory of Open Access Journals (Sweden)

    Paul M. Macey

    2018-01-01

    Full Text Available RationaleObstructive sleep apnea (OSA affects 2–5% of all children and is associated with cognitive and behavioral deficits, resulting in poor school performance. These psychological deficits may arise from brain injury, as seen in preliminary findings of lower gray matter volume among pediatric OSA patients. However, the psychological deficits in OSA are closely related to functions in the cortex, and such brain areas have not been specifically assessed. The objective was to determine whether cortical thickness, a marker of possible brain injury, is altered in children with OSA.MethodsWe examined regional brain cortical thicknesses using high-resolution T1-weighted magnetic resonance images in 16 pediatric OSA patients (8 males; mean age ± SD = 8.4 ± 1.2 years; mean apnea/hypopnea index ± SD = 11 ± 6 events/h and 138 controls (8.3 ± 1.1 years; 62 male; 138 subjects from the NIH Pediatric MRI database to identify cortical thickness differences in pediatric OSA subjects.ResultsCortical thinning occurred in multiple regions including the superior frontal, ventral medial prefrontal, and superior parietal cortices. The left side showed greater thinning in the superior frontal cortex. Cortical thickening was observed in bilateral precentral gyrus, mid-to-posterior insular cortices, and left central gyrus, as well as right anterior insula cortex.ConclusionChanges in cortical thickness are present in children with OSA and likely indicate disruption to neural developmental processes, including maturational patterns of cortical volume increases and synaptic pruning. Regions with thicker cortices may reflect inflammation or astrocyte activation. Both the thinning and thickening associated with OSA in children may contribute to the cognitive and behavioral dysfunction frequently found in the condition.

  11. Cortical Response Variability as a Developmental Index of Selective Auditory Attention

    Science.gov (United States)

    Strait, Dana L.; Slater, Jessica; Abecassis, Victor; Kraus, Nina

    2014-01-01

    Attention induces synchronicity in neuronal firing for the encoding of a given stimulus at the exclusion of others. Recently, we reported decreased variability in scalp-recorded cortical evoked potentials to attended compared with ignored speech in adults. Here we aimed to determine the developmental time course for this neural index of auditory…

  12. The maturation of cortical sleep rhythms and networks over early development

    OpenAIRE

    Chu, Catherine Jean; Leahy, J.; Pathmanathan, Jay Sriram; Kramer, M.A.; Cash, Sydney S.

    2014-01-01

    Objective: Although neuronal activity drives all aspects of cortical development, how human brain rhythms spontaneously mature remains an active area of research. We sought to systematically evaluate the emergence of human brain rhythms and functional cortical networks over early development. Methods: We examined cortical rhythms and coupling patterns from birth through adolescence in a large cohort of healthy children (n=384) using scalp electroencephalogram (EEG) in the sleep state. ...

  13. A compact and realistic cerebral cortical layout derived from prewhitened resting-state fMRI time series: Cherniak's adjacency rule, size law, and metamodule grouping upheld.

    Science.gov (United States)

    Lewis, Scott M; Christova, Peka; Jerde, Trenton A; Georgopoulos, Apostolos P

    2012-01-01

    We used hierarchical tree clustering to derive a functional organizational chart of 52 human cortical areas (26 per hemisphere) from zero-lag correlations calculated between single-voxel, prewhitened, resting-state BOLD fMRI time series in 18 subjects. No special "resting-state networks" were identified. There were four major features in the resulting tree (dendrogram). First, there was a strong clustering of homotopic, left-right hemispheric areas. Second, cortical areas were concatenated in multiple, partially overlapping clusters. Third, the arrangement of the areas revealed a layout that closely resembled the actual layout of the cerebral cortex, namely an orderly progression from anterior to posterior. And fourth, the layout of the cortical areas in the tree conformed to principles of efficient, compact layout of components proposed by Cherniak. Since the tree was derived on the basis of the strength of neural correlations, these results document an orderly relation between functional interactions and layout, i.e., between structure and function.

  14. A compact and realistic cerebral cortical layout derived from prewhitened resting-state fMRI time series: Cherniak's adjacency rule, size law, and metamodule grouping upheld

    Science.gov (United States)

    Lewis, Scott M.; Christova, Peka; Jerde, Trenton A.; Georgopoulos, Apostolos P.

    2012-01-01

    We used hierarchical tree clustering to derive a functional organizational chart of 52 human cortical areas (26 per hemisphere) from zero-lag correlations calculated between single-voxel, prewhitened, resting-state BOLD fMRI time series in 18 subjects. No special “resting-state networks” were identified. There were four major features in the resulting tree (dendrogram). First, there was a strong clustering of homotopic, left-right hemispheric areas. Second, cortical areas were concatenated in multiple, partially overlapping clusters. Third, the arrangement of the areas revealed a layout that closely resembled the actual layout of the cerebral cortex, namely an orderly progression from anterior to posterior. And fourth, the layout of the cortical areas in the tree conformed to principles of efficient, compact layout of components proposed by Cherniak. Since the tree was derived on the basis of the strength of neural correlations, these results document an orderly relation between functional interactions and layout, i.e., between structure and function. PMID:22973198

  15. Shindigs, brunches, and rodeos: the neural basis of event words.

    Science.gov (United States)

    Bedny, Marina; Dravida, Swethasri; Saxe, Rebecca

    2014-09-01

    Events (e.g., "running" or "eating") constitute a basic type within human cognition and human language. We asked whether thinking about events, as compared to other conceptual categories, depends on partially independent neural circuits. Indirect evidence for this hypothesis comes from previous studies showing elevated posterior temporal responses to verbs, which typically label events. Neural responses to verbs could, however, be driven either by their grammatical or by their semantic properties. In the present experiment, we separated the effects of grammatical class (verb vs. noun) and semantic category (event vs. object) by measuring neural responses to event nouns (e.g., "the hurricane"). Participants rated the semantic relatedness of event nouns, as well as of two categories of object nouns-animals (e.g., "the alligator") and plants (e.g., "the acorn")-and three categories of verbs-manner of motion (e.g., "to roll"), emission (e.g., "to sparkle"), and perception (e.g., "to gaze"). As has previously been observed, we found larger responses to verbs than to object nouns in the left posterior middle (LMTG) and superior (LSTG) temporal gyri. Crucially, we also found that the LMTG responds more to event than to object nouns. These data suggest that part of the posterior lateral temporal response to verbs is driven by their semantic properties. By contrast, a more superior region, at the junction of the temporal and parietal cortices, responded more to verbs than to all nouns, irrespective of their semantic category. We concluded that the neural mechanisms engaged when thinking about event and object categories are partially dissociable.

  16. Generation of Oligodendrogenic Spinal Neural Progenitor Cells From Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Khazaei, Mohamad; Ahuja, Christopher S; Fehlings, Michael G

    2017-08-14

    This unit describes protocols for the efficient generation of oligodendrogenic neural progenitor cells (o-NPCs) from human induced pluripotent stem cells (hiPSCs). Specifically, detailed methods are provided for the maintenance and differentiation of hiPSCs, human induced pluripotent stem cell-derived neural progenitor cells (hiPS-NPCs), and human induced pluripotent stem cell-oligodendrogenic neural progenitor cells (hiPSC-o-NPCs) with the final products being suitable for in vitro experimentation or in vivo transplantation. Throughout, cell exposure to growth factors and patterning morphogens has been optimized for both concentration and timing, based on the literature and empirical experience, resulting in a robust and highly efficient protocol. Using this derivation procedure, it is possible to obtain millions of oligodendrogenic-NPCs within 40 days of initial cell plating which is substantially shorter than other protocols for similar cell types. This protocol has also been optimized to use translationally relevant human iPSCs as the parent cell line. The resultant cells have been extensively characterized both in vitro and in vivo and express key markers of an oligodendrogenic lineage. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley and Sons, Inc.

  17. Direct Neural Conversion from Human Fibroblasts Using Self-Regulating and Nonintegrating Viral Vectors

    Directory of Open Access Journals (Sweden)

    Shong Lau

    2014-12-01

    Full Text Available Summary: Recent findings show that human fibroblasts can be directly programmed into functional neurons without passing via a proliferative stem cell intermediate. These findings open up the possibility of generating subtype-specific neurons of human origin for therapeutic use from fetal cell, from patients themselves, or from matched donors. In this study, we present an improved system for direct neural conversion of human fibroblasts. The neural reprogramming genes are regulated by the neuron-specific microRNA, miR-124, such that each cell turns off expression of the reprogramming genes once the cell has reached a stable neuronal fate. The regulated system can be combined with integrase-deficient vectors, providing a nonintegrative and self-regulated conversion system that rids problems associated with the integration of viral transgenes into the host genome. These modifications make the system suitable for clinical use and therefore represent a major step forward in the development of induced neurons for cell therapy. : Lau et al. now use miRNA targeting to build a self-regulating neural conversion system. Combined with nonintegrating vectors, this system can efficiently drive conversion of human fibroblasts into functional induced neurons (iNs suitable for clinical applications.

  18. Cortical morphometry in frontoparietal and default mode networks in math-gifted adolescents.

    Science.gov (United States)

    Navas-Sánchez, Francisco J; Carmona, Susana; Alemán-Gómez, Yasser; Sánchez-González, Javier; Guzmán-de-Villoria, Juan; Franco, Carolina; Robles, Olalla; Arango, Celso; Desco, Manuel

    2016-05-01

    Math-gifted subjects are characterized by above-age performance in intelligence tests, exceptional creativity, and high task commitment. Neuroimaging studies reveal enhanced functional brain organization and white matter microstructure in the frontoparietal executive network of math-gifted individuals. However, the cortical morphometry of these subjects remains largely unknown. The main goal of this study was to compare the cortical morphometry of math-gifted adolescents with that of an age- and IQ-matched control group. We used surface-based methods to perform a vertex-wise analysis of cortical thickness and surface area. Our results show that math-gifted adolescents present a thinner cortex and a larger surface area in key regions of the frontoparietal and default mode networks, which are involved in executive processing and creative thinking, respectively. The combination of reduced cortical thickness and larger surface area suggests above-age neural maturation of these networks in math-gifted individuals. Hum Brain Mapp 37:1893-1902, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Responses of single cells in cat visual cortex to prolonged stimulus movement: neural correlates of visual aftereffects.

    Science.gov (United States)

    Vautin, R G; Berkley, M A

    1977-09-01

    1. The activity of single cortical cells in area 17 of anesthetized and unanesthetized cats was recorded in response to prolonged stimulation with moving stimuli. 2. Under the appropriate conditions, all cells observed showed a progressive response decrement during the stimulation period, regardless of cell classification, i.e., simple, complex, or hypercomplex. 3. The observed response decrement was shown to be largely cortical in origin and could be adequately described with an exponential function of the form R = Rf +(R1-Rf)e-t/T. Time constants derived from such calculations yielded values ranging from 1.92 to 12.45 s under conditions of optimal-stimulation. 4. Most cells showed poststimulation effects, usually a brief period of reduced responsiveness that recovered exponentially. Recovery was essentially complete in about 5-35 s. 5. The degree to which stimuli were effective at inducing response was shown to have significant effects on the magnitude of the response decrement. 6. Several cells showed neural patterns of response and recovery that suggested the operation of intracortical inhibitory mechanisms. 7. A simple two-process model that adequately describes the behavior of all the studied cells is presented. 8. Because the properties of the cells studied correlate well with human psychophysical measures of contour and movement adaptation and recovery, a causal relationship to similar neural mechanisms in humans is suggested.

  20. Higher O-GlcNAc Levels Are Associated with Defects in Progenitor Proliferation and Premature Neuronal Differentiation during in-Vitro Human Embryonic Cortical Neurogenesis

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    Shama Parween

    2017-12-01

    Full Text Available The nutrient responsive O-GlcNAcylation is a dynamic post-translational protein modification found on several nucleocytoplasmic proteins. Previous studies have suggested that hyperglycemia induces the levels of total O-GlcNAcylation inside the cells. Hyperglycemia mediated increase in protein O-GlcNAcylation has been shown to be responsible for various pathologies including insulin resistance and Alzheimer's disease. Since maternal hyperglycemia during pregnancy is associated with adverse neurodevelopmental outcomes in the offspring, it is intriguing to identify the effect of increased protein O-GlcNAcylation on embryonic neurogenesis. Herein using human embryonic stem cells (hESCs as model, we show that increased levels of total O-GlcNAc is associated with decreased neural progenitor proliferation and premature differentiation of cortical neurons, reduced AKT phosphorylation, increased apoptosis and defects in the expression of various regulators of embryonic corticogenesis. As defects in proliferation and differentiation during neurodevelopment are common features of various neurodevelopmental disorders, increased O-GlcNAcylation could be one mechanism responsible for defective neurodevelopmental outcomes in metabolically compromised pregnancies such as diabetes.

  1. A model for integrating elementary neural functions into delayed-response behavior.

    Directory of Open Access Journals (Sweden)

    Thomas Gisiger

    2006-04-01

    Full Text Available It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning, and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task, or recalling from this image another one that has been associated with it during training (delayed-pair association task. The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

  2. A model for integrating elementary neural functions into delayed-response behavior.

    Science.gov (United States)

    Gisiger, Thomas; Kerszberg, Michel

    2006-04-01

    It is well established that various cortical regions can implement a wide array of neural processes, yet the mechanisms which integrate these processes into behavior-producing, brain-scale activity remain elusive. We propose that an important role in this respect might be played by executive structures controlling the traffic of information between the cortical regions involved. To illustrate this hypothesis, we present a neural network model comprising a set of interconnected structures harboring stimulus-related activity (visual representation, working memory, and planning), and a group of executive units with task-related activity patterns that manage the information flowing between them. The resulting dynamics allows the network to perform the dual task of either retaining an image during a delay (delayed-matching to sample task), or recalling from this image another one that has been associated with it during training (delayed-pair association task). The model reproduces behavioral and electrophysiological data gathered on the inferior temporal and prefrontal cortices of primates performing these same tasks. It also makes predictions on how neural activity coding for the recall of the image associated with the sample emerges and becomes prospective during the training phase. The network dynamics proves to be very stable against perturbations, and it exhibits signs of scale-invariant organization and cooperativity. The present network represents a possible neural implementation for active, top-down, prospective memory retrieval in primates. The model suggests that brain activity leading to performance of cognitive tasks might be organized in modular fashion, simple neural functions becoming integrated into more complex behavior by executive structures harbored in prefrontal cortex and/or basal ganglia.

  3. Neural mechanisms of memory retrieval: role of the prefrontal cortex.

    Science.gov (United States)

    Hasegawa, I

    2000-01-01

    In the primate brain, long-term memory is stored in the neocortical association area which is also engaged in sensory perception. The coded representation of memory is retrieved via interactions of hierarchically different cortical areas along bottom-up and top-down anatomical connections. The functional significance of the fronto-cortical top-down neuronal projections has been relevantly assessed in a new experimental paradigm using posterior-split-brain monkeys. When the splenium of the corpus callosum and the anterior commissure were selectively split, the bottom-up visual signal originating from the unilateral striate cortex could not reach the contralateral visual cortical areas. In this preparation, long-term memory acquired through visual stimulus-stimulus association learning was prevented from transferring across hemispheres. Nonetheless, following the presentation of a visual cue to one hemisphere, the prefrontal cortex could instruct the contralateral hemisphere to retrieve the correct stimulus specified by the cue. These results support the hypothesis that the prefrontal cortex can regulate memory recall in the absence of bottom-up sensory input. In humans, functional neuroimaging studies have revealed activation of a distributed neural network, including the prefrontal cortex, during memory retrieval tasks. Thus, the prefrontal cortex is consistently involved in retrieval of long-term memory in primates.

  4. Differential patterns of cortical activation as a function of fluid reasoning complexity.

    Science.gov (United States)

    Perfetti, Bernardo; Saggino, Aristide; Ferretti, Antonio; Caulo, Massimo; Romani, Gian Luca; Onofrj, Marco

    2009-02-01

    Fluid intelligence (gf) refers to abstract reasoning and problem solving abilities. It is considered a human higher cognitive factor central to general intelligence (g). The regions of the cortex supporting gf have been revealed by recent bioimaging studies and valuable hypothesis on the neural correlates of individual differences have been proposed. However, little is known about the interaction between individual variability in gf and variation in cortical activity following task complexity increase. To further investigate this, two samples of participants (high-IQ, N = 8; low-IQ, N = 10) with significant differences in gf underwent two reasoning (moderate and complex) tasks and a control task adapted from the Raven progressive matrices. Functional magnetic resonance was used and the recorded signal analyzed between and within the groups. The present study revealed two opposite patterns of neural activity variation which were probably a reflection of the overall differences in cognitive resource modulation: when complexity increased, high-IQ subjects showed a signal enhancement in some frontal and parietal regions, whereas low-IQ subjects revealed a decreased activity in the same areas. Moreover, a direct comparison between the groups' activation patterns revealed a greater neural activity in the low-IQ sample when conducting moderate task, with a strong involvement of medial and lateral frontal regions thus suggesting that the recruitment of executive functioning might be different between the groups. This study provides evidence for neural differences in facing reasoning complexity among subjects with different gf level that are mediated by specific patterns of activation of the underlying fronto-parietal network.

  5. Efficient decoding with steady-state Kalman filter in neural interface systems.

    Science.gov (United States)

    Malik, Wasim Q; Truccolo, Wilson; Brown, Emery N; Hochberg, Leigh R

    2011-02-01

    The Kalman filter is commonly used in neural interface systems to decode neural activity and estimate the desired movement kinematics. We analyze a low-complexity Kalman filter implementation in which the filter gain is approximated by its steady-state form, computed offline before real-time decoding commences. We evaluate its performance using human motor cortical spike train data obtained from an intracortical recording array as part of an ongoing pilot clinical trial. We demonstrate that the standard Kalman filter gain converges to within 95% of the steady-state filter gain in 1.5±0.5 s (mean ±s.d.). The difference in the intended movement velocity decoded by the two filters vanishes within 5 s, with a correlation coefficient of 0.99 between the two decoded velocities over the session length. We also find that the steady-state Kalman filter reduces the computational load (algorithm execution time) for decoding the firing rates of 25±3 single units by a factor of 7.0±0.9. We expect that the gain in computational efficiency will be much higher in systems with larger neural ensembles. The steady-state filter can thus provide substantial runtime efficiency at little cost in terms of estimation accuracy. This far more efficient neural decoding approach will facilitate the practical implementation of future large-dimensional, multisignal neural interface systems.

  6. Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

    Directory of Open Access Journals (Sweden)

    Hui-Fang Chang

    Full Text Available We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz. The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

  7. Pulsed DC Electric Field-Induced Differentiation of Cortical Neural Precursor Cells.

    Science.gov (United States)

    Chang, Hui-Fang; Lee, Ying-Shan; Tang, Tang K; Cheng, Ji-Yen

    2016-01-01

    We report the differentiation of neural stem and progenitor cells solely induced by direct current (DC) pulses stimulation. Neural stem and progenitor cells in the adult mammalian brain are promising candidates for the development of therapeutic neuroregeneration strategies. The differentiation of neural stem and progenitor cells depends on various in vivo environmental factors, such as nerve growth factor and endogenous EF. In this study, we demonstrated that the morphologic and phenotypic changes of mouse neural stem and progenitor cells (mNPCs) could be induced solely by exposure to square-wave DC pulses (magnitude 300 mV/mm at frequency of 100-Hz). The DC pulse stimulation was conducted for 48 h, and the morphologic changes of mNPCs were monitored continuously. The length of primary processes and the amount of branching significantly increased after stimulation by DC pulses for 48 h. After DC pulse treatment, the mNPCs differentiated into neurons, astrocytes, and oligodendrocytes simultaneously in stem cell maintenance medium. Our results suggest that simple DC pulse treatment could control the fate of NPCs. With further studies, DC pulses may be applied to manipulate NPC differentiation and may be used for the development of therapeutic strategies that employ NPCs to treat nervous system disorders.

  8. Attention enhances multi-voxel representation of novel objects in frontal, parietal and visual cortices.

    Science.gov (United States)

    Woolgar, Alexandra; Williams, Mark A; Rich, Anina N

    2015-04-01

    Selective attention is fundamental for human activity, but the details of its neural implementation remain elusive. One influential theory, the adaptive coding hypothesis (Duncan, 2001, An adaptive coding model of neural function in prefrontal cortex, Nature Reviews Neuroscience 2:820-829), proposes that single neurons in certain frontal and parietal regions dynamically adjust their responses to selectively encode relevant information. This selective representation may in turn support selective processing in more specialized brain regions such as the visual cortices. Here, we use multi-voxel decoding of functional magnetic resonance images to demonstrate selective representation of attended--and not distractor--objects in frontal, parietal, and visual cortices. In addition, we highlight a critical role for task demands in determining which brain regions exhibit selective coding. Strikingly, representation of attended objects in frontoparietal cortex was highest under conditions of high perceptual demand, when stimuli were hard to perceive and coding in early visual cortex was weak. Coding in early visual cortex varied as a function of attention and perceptual demand, while coding in higher visual areas was sensitive to the allocation of attention but robust to changes in perceptual difficulty. Consistent with high-profile reports, peripherally presented objects could also be decoded from activity at the occipital pole, a region which corresponds to the fovea. Our results emphasize the flexibility of frontoparietal and visual systems. They support the hypothesis that attention enhances the multi-voxel representation of information in the brain, and suggest that the engagement of this attentional mechanism depends critically on current task demands. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Neural representations of kinematic laws of motion: evidence for action-perception coupling.

    Science.gov (United States)

    Dayan, Eran; Casile, Antonino; Levit-Binnun, Nava; Giese, Martin A; Hendler, Talma; Flash, Tamar

    2007-12-18

    Behavioral and modeling studies have established that curved and drawing human hand movements obey the 2/3 power law, which dictates a strong coupling between movement curvature and velocity. Human motion perception seems to reflect this constraint. The functional MRI study reported here demonstrates that the brain's response to this law of motion is much stronger and more widespread than to other types of motion. Compliance with this law is reflected in the activation of a large network of brain areas subserving motor production, visual motion processing, and action observation functions. Hence, these results strongly support the notion of similar neural coding for motion perception and production. These findings suggest that cortical motion representations are optimally tuned to the kinematic and geometrical invariants characterizing biological actions.

  10. 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.

  11. Subcortical and cortical correlates of pitch discrimination: Evidence for two levels of neuroplasticity in musicians

    DEFF Research Database (Denmark)

    Bianchi, Federica; Hjortkjær, Jens; Santurette, Sébastien

    2017-01-01

    superior temporal gyrus, Heschl's gyrus, insular cortex, inferior frontal gyrus, and in the inferior colliculus. Both subcortical and cortical neural responses predicted the individual pitch-discrimination performance. However, functional activity in the inferior colliculus correlated with differences...

  12. Human umbilical cord blood cells restore brain damage induced changes in rat somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Maren Geissler

    Full Text Available Intraperitoneal transplantation of human umbilical cord blood (hUCB cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury.

  13. The significance of crack-resistance curves to the mixed-mode fracture toughness of human cortical bone

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, Elizabeth A.; Launey, Maximilien E.; Ritchie, Robert O.

    2010-03-25

    The majority of fracture mechanics studies on the toughness of bone have been performed under tensile loading. However, it has recently been shown that the toughness of human cortical bone in the transverse (breaking) orientation is actually much lower in shear (mode II) than in tension (mode I); a fact that is physiologically relevant as in vivo bone is invariably loaded multiaxially. Since bone is a material that derives its fracture resistance primarily during crack growth through extrinsic toughening mechanisms, such as crack deflection and bridging, evaluation of its toughness is best achieved through measurements of the crack-resistance or R-curve, which describes the fracture toughness as a function of crack extension. Accordingly, in this study, we attempt to measure for the first time the R-curve fracture toughness of human cortical bone under physiologically relevant mixed-mode loading conditions. We show that the resulting mixed-mode (mode I + II) toughness depends strongly on the crack trajectory and is the result of the competition between the paths of maximum mechanical driving force and 'weakest' microstructural resistance.

  14. Wnt/Yes-Associated Protein Interactions During Neural Tissue Patterning of Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Bejoy, Julie; Song, Liqing; Zhou, Yi; Li, Yan

    2018-04-01

    Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain-like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests. However, the interactions between Wnt and YAP expression for neural lineage commitment of hiPSCs remain poorly explored. The objective of this study is to investigate the effects of Wnt signaling and YAP expression on the cellular population in three-dimensional (3D) neural spheroids derived from hiPSCs. In this study, Wnt signaling was activated using CHIR99021 for 3D neural spheroids derived from human iPSK3 cells through embryoid body formation. Our results indicate that Wnt activation induces nuclear localization of YAP and upregulates the expression of HOXB4, the marker for hindbrain/spinal cord. By contrast, the cells exhibit more rostral forebrain neural identity (expression of TBR1) without Wnt activation. Cytochalasin D was then used to induce cytoplasmic YAP and the results showed the decreased HOXB4 expression. In addition, the incorporation of microparticles in the neural spheroids was investigated for the perturbation of neural patterning. This study may indicate the bidirectional interactions of Wnt signaling and YAP expression during neural tissue patterning, which have the significance in neurological disease modeling, drug screening, and neural tissue regeneration.

  15. Neural representations of social status hierarchy in human inferior parietal cortex.

    Science.gov (United States)

    Chiao, Joan Y; Harada, Tokiko; Oby, Emily R; Li, Zhang; Parrish, Todd; Bridge, Donna J

    2009-01-01

    Mental representations of social status hierarchy share properties with that of numbers. Previous neuroimaging studies have shown that the neural representation of numerical magnitude lies within a network of regions within inferior parietal cortex. However the neural basis of social status hierarchy remains unknown. Using fMRI, we studied subjects while they compared social status magnitude of people, objects and symbols, as well as numerical magnitude. Both social status and number comparisons recruited bilateral intraparietal sulci. We also observed a semantic distance effect whereby neural activity within bilateral intraparietal sulci increased for semantically close relative to far numerical and social status comparisons. These results demonstrate that social status and number comparisons recruit distinct and overlapping neuronal representations within human inferior parietal cortex.

  16. Populations of auditory cortical neurons can accurately encode acoustic space across stimulus intensity.

    Science.gov (United States)

    Miller, Lee M; Recanzone, Gregg H

    2009-04-07

    The auditory cortex is critical for perceiving a sound's location. However, there is no topographic representation of acoustic space, and individual auditory cortical neurons are often broadly tuned to stimulus location. It thus remains unclear how acoustic space is represented in the mammalian cerebral cortex and how it could contribute to sound localization. This report tests whether the firing rates of populations of neurons in different auditory cortical fields in the macaque monkey carry sufficient information to account for horizontal sound localization ability. We applied an optimal neural decoding technique, based on maximum likelihood estimation, to populations of neurons from 6 different cortical fields encompassing core and belt areas. We found that the firing rate of neurons in the caudolateral area contain enough information to account for sound localization ability, but neurons in other tested core and belt cortical areas do not. These results provide a detailed and plausible population model of how acoustic space could be represented in the primate cerebral cortex and support a dual stream processing model of auditory cortical processing.

  17. Spatial interactions reveal inhibitory cortical networks in human amblyopia.

    Science.gov (United States)

    Wong, Erwin H; Levi, Dennis M; McGraw, Paul V

    2005-10-01

    Humans with amblyopia have a well-documented loss of sensitivity for first-order, or luminance defined, visual information. Recent studies show that they also display a specific loss of sensitivity for second-order, or contrast defined, visual information; a type of image structure encoded by neurons found predominantly in visual area A18/V2. In the present study, we investigate whether amblyopia disrupts the normal architecture of spatial interactions in V2 by determining the contrast detection threshold of a second-order target in the presence of second-order flanking stimuli. Adjacent flanks facilitated second-order detectability in normal observers. However, in marked contrast, they suppressed detection in each eye of the majority of amblyopic observers. Furthermore, strabismic observers with no loss of visual acuity show a similar pattern of detection suppression. We speculate that amblyopia results in predominantly inhibitory cortical interactions between second-order neurons.

  18. Neuroanatomical correlates of tinnitus revealed by cortical thickness analysis and diffusion tensor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Aldhafeeri, Faten M [The University of Liverpool, Department of Medical Imaging, School of Health Sciences, Liverpool (United Kingdom); King Khalid General Hospital, Ministry of Health, Radiology Department, Hafral-batin (Saudi Arabia); Mackenzie, Ian; Kay, Tony [Aintree University Hospitals NHS Foundation Trust, Liverpool (United Kingdom); Alghamdi, Jamaan [The University of Liverpool, Department of Medical Imaging, School of Health Sciences, Liverpool (United Kingdom); King Abdul Aziz University, Physics Department, Faculty of Sciences, Jeddah (Saudi Arabia); Sluming, Vanessa [The University of Liverpool, Department of Medical Imaging, School of Health Sciences, Liverpool (United Kingdom); Magnetic Resonance and Image Analysis Research Centre, Liverpool (United Kingdom)

    2012-08-15

    Tinnitus is a poorly understood auditory perception of sound in the absence of external stimuli. Convergent evidence proposes that tinnitus perception involves brain structural alterations as part of its pathophysiology. The aim of this study is to investigate the structural brain changes that might be associated with tinnitus-related stress and negative emotions. Using high-resolution magnetic resonance imaging and diffusion tensor imaging, we investigated grey matter and white matter (WM) alterations by estimating cortical thickness measures, fractional anisotropy and mean diffusivity in 14 tinnitus subjects and 14 age- and sex-matched non-tinnitus subjects. Significant cortical thickness reductions were found in the prefrontal cortex (PFC), temporal lobe and limbic system in tinnitus subjects compared to non-tinnitus subjects. Tinnitus sufferers were found to have disrupted WM integrity in tracts involving connectivity of the PFC, temporal lobe, thalamus and limbic system. Our results suggest that such neural changes may represent neural origins for tinnitus or consequences of tinnitus and its associations. (orig.)

  19. Neuroanatomical correlates of tinnitus revealed by cortical thickness analysis and diffusion tensor imaging

    International Nuclear Information System (INIS)

    Aldhafeeri, Faten M.; Mackenzie, Ian; Kay, Tony; Alghamdi, Jamaan; Sluming, Vanessa

    2012-01-01

    Tinnitus is a poorly understood auditory perception of sound in the absence of external stimuli. Convergent evidence proposes that tinnitus perception involves brain structural alterations as part of its pathophysiology. The aim of this study is to investigate the structural brain changes that might be associated with tinnitus-related stress and negative emotions. Using high-resolution magnetic resonance imaging and diffusion tensor imaging, we investigated grey matter and white matter (WM) alterations by estimating cortical thickness measures, fractional anisotropy and mean diffusivity in 14 tinnitus subjects and 14 age- and sex-matched non-tinnitus subjects. Significant cortical thickness reductions were found in the prefrontal cortex (PFC), temporal lobe and limbic system in tinnitus subjects compared to non-tinnitus subjects. Tinnitus sufferers were found to have disrupted WM integrity in tracts involving connectivity of the PFC, temporal lobe, thalamus and limbic system. Our results suggest that such neural changes may represent neural origins for tinnitus or consequences of tinnitus and its associations. (orig.)

  20. A cortical network model of cognitive and emotional influences in human decision making.

    Science.gov (United States)

    Nazir, Azadeh Hassannejad; Liljenström, Hans

    2015-10-01

    Decision making (DM)(2) is a complex process that appears to involve several brain structures. In particular, amygdala, orbitofrontal cortex (OFC) and lateral prefrontal cortex (LPFC) seem to be essential in human decision making, where both emotional and cognitive aspects are taken into account. In this paper, we present a computational network model representing the neural information processing of DM, from perception to behavior. We model the population dynamics of the three neural structures (amygdala, OFC and LPFC), as well as their interaction. In our model, the neurodynamic activity of amygdala and OFC represents the neural correlates of secondary emotion, while the activity of certain neural populations in OFC alone represents the outcome expectancy of different options. The cognitive/rational aspect of DM is associated with LPFC. Our model is intended to give insights on the emotional and cognitive processes involved in DM under various internal and external contexts. Different options for actions are represented by the oscillatory activity of cell assemblies, which may change due to experience and learning. Knowledge and experience of the outcome of our decisions and actions can eventually result in changes in our neural structures, attitudes and behaviors. Simulation results may have implications for how we make decisions for our individual actions, as well as for societal choices, where we take examples from transport and its impact on CO2 emissions and climate change. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Electro-acupuncture exerts beneficial effects against cerebral ischemia and promotes the proliferation of neural progenitor cells in the cortical peri-infarct area through the Wnt/β-catenin signaling pathway

    Science.gov (United States)

    CHEN, BIN; TAO, JING; LIN, YUKUN; LIN, RUHUI; LIU, WEILIN; CHEN, LIDIAN

    2015-01-01

    Electro-acupuncture (EA) is a novel therapy based on combining traditional acupuncture with modern electrotherapy, and it is currently being investigated as a treatment for ischemic stroke. In the present study, we aimed to investigate the mechanisms through which EA regulates the proliferation of neural progenitor cells (NPCs) in the cortical peri-infarct area after stroke. The neuroprotective effects of EA on ischemic rats were evaluated by determining the neurological deficit scores and cerebral infarct volumes. The proliferation of the NPCs and the activation of the Wnt/β-catenin signaling pathway in the cortical peri-infarct area were examined. Our results revealed that EA significantly alleviated neurological deficits, reduced the infarct volume and enhanced NPC proliferation [nestin/glial fibrillary acidic protein (GFAP)-double positive] in the cortex of rats subjected to middle cerebral artery occlusion (MCAO). Moreover, the Wnt1 and β-catenin mRNA and protein levels were increased, while glycogen synthase kinase-3 (GSK3) transcription was suppressed by EA. These results suggest that the upregulatory effects of EA on the Wnt/β-catenin signaling pathway may promote NPC proliferation in the cortical peri-infarct area after stroke, consequently providing a therapeutic effect against cerebral ischemia. PMID:26329606

  2. Connectivities and synchronous firing in cortical neuronal networks

    International Nuclear Information System (INIS)

    Jia, L.C.; Sano, M.; Lai, P.-Y.; Chan, C.K.

    2004-01-01

    Network connectivities (k-bar) of cortical neural cultures are studied by synchronized firing and determined from measured correlations between fluorescence intensities of firing neurons. The bursting frequency (f) during synchronized firing of the networks is found to be an increasing function of k-bar. With f taken to be proportional to k-bar, a simple random model with a k-bar dependent connection probability p(k-bar) has been constructed to explain our experimental findings successfully

  3. Distinct pathways of neural coupling for different basic emotions.

    Science.gov (United States)

    Tettamanti, Marco; Rognoni, Elena; Cafiero, Riccardo; Costa, Tommaso; Galati, Dario; Perani, Daniela

    2012-01-16

    Emotions are complex events recruiting distributed cortical and subcortical cerebral structures, where the functional integration dynamics within the involved neural circuits in relation to the nature of the different emotions are still unknown. Using fMRI, we measured the neural responses elicited by films representing basic emotions (fear, disgust, sadness, happiness). The amygdala and the associative cortex were conjointly activated by all basic emotions. Furthermore, distinct arrays of cortical and subcortical brain regions were additionally activated by each emotion, with the exception of sadness. Such findings informed the definition of three effective connectivity models, testing for the functional integration of visual cortex and amygdala, as regions processing all emotions, with domain-specific regions, namely: i) for fear, the frontoparietal system involved in preparing adaptive motor responses; ii) for disgust, the somatosensory system, reflecting protective responses against contaminating stimuli; iii) for happiness: medial prefrontal and temporoparietal cortices involved in understanding joyful interactions. Consistently with these domain-specific models, the results of the effective connectivity analysis indicate that the amygdala is involved in distinct functional integration effects with cortical networks processing sensorimotor, somatosensory, or cognitive aspects of basic emotions. The resulting effective connectivity networks may serve to regulate motor and cognitive behavior based on the quality of the induced emotional experience. Copyright © 2011. Published by Elsevier Inc.

  4. Response variance in functional maps: neural darwinism revisited.

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    Hirokazu Takahashi

    Full Text Available The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population.

  5. Response variance in functional maps: neural darwinism revisited.

    Science.gov (United States)

    Takahashi, Hirokazu; Yokota, Ryo; Kanzaki, Ryohei

    2013-01-01

    The mechanisms by which functional maps and map plasticity contribute to cortical computation remain controversial. Recent studies have revisited the theory of neural Darwinism to interpret the learning-induced map plasticity and neuronal heterogeneity observed in the cortex. Here, we hypothesize that the Darwinian principle provides a substrate to explain the relationship between neuron heterogeneity and cortical functional maps. We demonstrate in the rat auditory cortex that the degree of response variance is closely correlated with the size of its representational area. Further, we show that the response variance within a given population is altered through training. These results suggest that larger representational areas may help to accommodate heterogeneous populations of neurons. Thus, functional maps and map plasticity are likely to play essential roles in Darwinian computation, serving as effective, but not absolutely necessary, structures to generate diverse response properties within a neural population.

  6. Human Inspired Self-developmental Model of Neural Network (HIM): Introducing Content/Form Computing

    Science.gov (United States)

    Krajíček, Jiří

    This paper presents cross-disciplinary research between medical/psychological evidence on human abilities and informatics needs to update current models in computer science to support alternative methods for computation and communication. In [10] we have already proposed hypothesis introducing concept of human information model (HIM) as cooperative system. Here we continue on HIM design in detail. In our design, first we introduce Content/Form computing system which is new principle of present methods in evolutionary computing (genetic algorithms, genetic programming). Then we apply this system on HIM (type of artificial neural network) model as basic network self-developmental paradigm. Main inspiration of our natural/human design comes from well known concept of artificial neural networks, medical/psychological evidence and Sheldrake theory of "Nature as Alive" [22].

  7. Directed cortical information flow during human object recognition: analyzing induced EEG gamma-band responses in brain's source space.

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    Gernot G Supp

    Full Text Available The increase of induced gamma-band responses (iGBRs; oscillations >30 Hz elicited by familiar (meaningful objects is well established in electroencephalogram (EEG research. This frequency-specific change at distinct locations is thought to indicate the dynamic formation of local neuronal assemblies during the activation of cortical object representations. As analytically power increase is just a property of a single location, phase-synchrony was introduced to investigate the formation of large-scale networks between spatially distant brain sites. However, classical phase-synchrony reveals symmetric, pair-wise correlations and is not suited to uncover the directionality of interactions. Here, we investigated the neural mechanism of visual object processing by means of directional coupling analysis going beyond recording sites, but rather assessing the directionality of oscillatory interactions between brain areas directly. This study is the first to identify the directionality of oscillatory brain interactions in source space during human object recognition and suggests that familiar, but not unfamiliar, objects engage widespread reciprocal information flow. Directionality of cortical information-flow was calculated based upon an established Granger-Causality coupling-measure (partial-directed coherence; PDC using autoregressive modeling. To enable comparison with previous coupling studies lacking directional information, phase-locking analysis was applied, using wavelet-based signal decompositions. Both, autoregressive modeling and wavelet analysis, revealed an augmentation of iGBRs during the presentation of familiar objects relative to unfamiliar controls, which was localized to inferior-temporal, superior-parietal and frontal brain areas by means of distributed source reconstruction. The multivariate analysis of PDC evaluated each possible direction of brain interaction and revealed widespread reciprocal information-transfer during familiar

  8. Tactile spatial working memory activates the dorsal extrastriate cortical pathway in congenitally blind individuals.

    Science.gov (United States)

    Bonino, D; Ricciardi, E; Sani, L; Gentili, C; Vanello, N; Guazzelli, M; Vecchi, T; Pietrini, P

    2008-09-01

    In sighted individuals, both the visual and tactile version of the same spatial working memory task elicited neural responses in the dorsal "where" cortical pathway (Ricciardi et al., 2006). Whether the neural response during the tactile working memory task is due to visually-based spatial imagery or rather reflects a more abstract, supramodal organization of the dorsal cortical pathway remains to be determined. To understand the role of visual experience on the functional organization of the dorsal cortical stream, using functional magnetic resonance imaging (fMRI) here we examined brain response in four individuals with congenital or early blindness and no visual recollection, while they performed the same tactile spatial working memory task, a one-back recognition of 2D and 3D matrices. The blind subjects showed a significant activation in bilateral posterior parietal cortex, dorsolateral and inferior prefrontal areas, precuneus, lateral occipital cortex, and cerebellum. Thus, dorsal occipito-parietal areas are involved in mental imagery dealing with spatial components in subjects without prior visual experience and in response to a non-visual task. These data indicate that recruitment of the dorsal cortical pathway in response to the tactile spatial working memory task is not mediated by visually-based imagery and that visual experience is not a prerequisite for the development of a more abstract functional organization of the dorsal stream. These findings, along with previous data indicating a similar supramodal functional organization within the ventral cortical pathway and the motion processing brain regions, may contribute to explain how individuals who are born deprived of sight are able to interact effectively with the surrounding world.

  9. Visuotactile motion congruence enhances gamma-band activity in visual and somatosensory cortices.

    Science.gov (United States)

    Krebber, Martin; Harwood, James; Spitzer, Bernhard; Keil, Julian; Senkowski, Daniel

    2015-08-15

    When touching and viewing a moving surface our visual and somatosensory systems receive congruent spatiotemporal input. Behavioral studies have shown that motion congruence facilitates interplay between visual and tactile stimuli, but the neural mechanisms underlying this interplay are not well understood. Neural oscillations play a role in motion processing and multisensory integration. They may also be crucial for visuotactile motion processing. In this electroencephalography study, we applied linear beamforming to examine the impact of visuotactile motion congruence on beta and gamma band activity (GBA) in visual and somatosensory cortices. Visual and tactile inputs comprised of gratings that moved either in the same or different directions. Participants performed a target detection task that was unrelated to motion congruence. While there were no effects in the beta band (13-21Hz), the power of GBA (50-80Hz) in visual and somatosensory cortices was larger for congruent compared with incongruent motion stimuli. This suggests enhanced bottom-up multisensory processing when visual and tactile gratings moved in the same direction. Supporting its behavioral relevance, GBA was correlated with shorter reaction times in the target detection task. We conclude that motion congruence plays an important role for the integrative processing of visuotactile stimuli in sensory cortices, as reflected by oscillatory responses in the gamma band. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Hearing with Two Ears: Evidence for Cortical Binaural Interaction during Auditory Processing.

    Science.gov (United States)

    Henkin, Yael; Yaar-Soffer, Yifat; Givon, Lihi; Hildesheimer, Minka

    2015-04-01

    Integration of information presented to the two ears has been shown to manifest in binaural interaction components (BICs) that occur along the ascending auditory pathways. In humans, BICs have been studied predominantly at the brainstem and thalamocortical levels; however, understanding of higher cortically driven mechanisms of binaural hearing is limited. To explore whether BICs are evident in auditory event-related potentials (AERPs) during the advanced perceptual and postperceptual stages of cortical processing. The AERPs N1, P3, and a late negative component (LNC) were recorded from multiple site electrodes while participants performed an oddball discrimination task that consisted of natural speech syllables (/ka/ vs. /ta/) that differed by place-of-articulation. Participants were instructed to respond to the target stimulus (/ta/) while performing the task in three listening conditions: monaural right, monaural left, and binaural. Fifteen (21-32 yr) young adults (6 females) with normal hearing sensitivity. By subtracting the response to target stimuli elicited in the binaural condition from the sum of responses elicited in the monaural right and left conditions, the BIC waveform was derived and the latencies and amplitudes of the components were measured. The maximal interaction was calculated by dividing BIC amplitude by the summed right and left response amplitudes. In addition, the latencies and amplitudes of the AERPs to target stimuli elicited in the monaural right, monaural left, and binaural listening conditions were measured and subjected to analysis of variance with repeated measures testing the effect of listening condition and laterality. Three consecutive BICs were identified at a mean latency of 129, 406, and 554 msec, and were labeled N1-BIC, P3-BIC, and LNC-BIC, respectively. Maximal interaction increased significantly with progression of auditory processing from perceptual to postperceptual stages and amounted to 51%, 55%, and 75% of the sum of

  11. Investigations of the human visual system using functional magnetic resonance imaging (FMRI)

    International Nuclear Information System (INIS)

    Kollias, Spyros S.

    2004-01-01

    The application of functional magnetic resonance imaging (fMRI) in studies of the visual system provided significant advancement in our understanding of the organization and functional properties of visual areas in the human cortex. Recent technological and methodological improvements allowed studies to correlate neuronal activity with visual perception and demonstrated the ability of fMRI to observe distributed neural systems and to explore modulation of neural activity during higher cognitive processes. Preliminary applications in patients with visual impairments suggest that this method provides a powerful tool for the assessment and management of brain pathologies. Recent research focuses on obtaining new information about the spatial localization, organization, functional specialization and participation in higher cognitive functions of visual cortical areas in the living human brain and in further establishment of the method as a useful clinical tool of diagnostic and prognostic significance for various pathologic processes affecting the integrity of the visual system. It is anticipated that the combined neuroimaging approach in patients with lesions and healthy controls will provide new insight on the topography and functional specialization of cortical visual areas and will further establish the clinical value of the method for improving diagnostic accuracy and treatment planning

  12. Deep Recurrent Neural Networks for Human Activity Recognition

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    Abdulmajid Murad

    2017-11-01

    Full Text Available Adopting deep learning methods for human activity recognition has been effective in extracting discriminative features from raw input sequences acquired from body-worn sensors. Although human movements are encoded in a sequence of successive samples in time, typical machine learning methods perform recognition tasks without exploiting the temporal correlations between input data samples. Convolutional neural networks (CNNs address this issue by using convolutions across a one-dimensional temporal sequence to capture dependencies among input data. However, the size of convolutional kernels restricts the captured range of dependencies between data samples. As a result, typical models are unadaptable to a wide range of activity-recognition configurations and require fixed-length input windows. In this paper, we propose the use of deep recurrent neural networks (DRNNs for building recognition models that are capable of capturing long-range dependencies in variable-length input sequences. We present unidirectional, bidirectional, and cascaded architectures based on long short-term memory (LSTM DRNNs and evaluate their effectiveness on miscellaneous benchmark datasets. Experimental results show that our proposed models outperform methods employing conventional machine learning, such as support vector machine (SVM and k-nearest neighbors (KNN. Additionally, the proposed models yield better performance than other deep learning techniques, such as deep believe networks (DBNs and CNNs.

  13. Deep Recurrent Neural Networks for Human Activity Recognition.

    Science.gov (United States)

    Murad, Abdulmajid; Pyun, Jae-Young

    2017-11-06

    Adopting deep learning methods for human activity recognition has been effective in extracting discriminative features from raw input sequences acquired from body-worn sensors. Although human movements are encoded in a sequence of successive samples in time, typical machine learning methods perform recognition tasks without exploiting the temporal correlations between input data samples. Convolutional neural networks (CNNs) address this issue by using convolutions across a one-dimensional temporal sequence to capture dependencies among input data. However, the size of convolutional kernels restricts the captured range of dependencies between data samples. As a result, typical models are unadaptable to a wide range of activity-recognition configurations and require fixed-length input windows. In this paper, we propose the use of deep recurrent neural networks (DRNNs) for building recognition models that are capable of capturing long-range dependencies in variable-length input sequences. We present unidirectional, bidirectional, and cascaded architectures based on long short-term memory (LSTM) DRNNs and evaluate their effectiveness on miscellaneous benchmark datasets. Experimental results show that our proposed models outperform methods employing conventional machine learning, such as support vector machine (SVM) and k-nearest neighbors (KNN). Additionally, the proposed models yield better performance than other deep learning techniques, such as deep believe networks (DBNs) and CNNs.

  14. Integrated mechanisms of anticipation and rate-of-change computations in cortical circuits.

    Directory of Open Access Journals (Sweden)

    Gabriel D Puccini

    2007-05-01

    Full Text Available Local neocortical circuits are characterized by stereotypical physiological and structural features that subserve generic computational operations. These basic computations of the cortical microcircuit emerge through the interplay of neuronal connectivity, cellular intrinsic properties, and synaptic plasticity dynamics. How these interacting mechanisms generate specific computational operations in the cortical circuit remains largely unknown. Here, we identify the neurophysiological basis of both the rate of change and anticipation computations on synaptic inputs in a cortical circuit. Through biophysically realistic computer simulations and neuronal recordings, we show that the rate-of-change computation is operated robustly in cortical networks through the combination of two ubiquitous brain mechanisms: short-term synaptic depression and spike-frequency adaptation. We then show how this rate-of-change circuit can be embedded in a convergently connected network to anticipate temporally incoming synaptic inputs, in quantitative agreement with experimental findings on anticipatory responses to moving stimuli in the primary visual cortex. Given the robustness of the mechanism and the widespread nature of the physiological machinery involved, we suggest that rate-of-change computation and temporal anticipation are principal, hard-wired functions of neural information processing in the cortical microcircuit.

  15. Intralaminar and medial thalamic influence on cortical synchrony, information transmission and cognition

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    Yuri B Saalmann

    2014-05-01

    Full Text Available The intralaminar and medial thalamic nuclei are part of the higher-order thalamus, which receives little sensory input, and instead forms extensive cortico-thalamo-cortical pathways. The large mediodorsal thalamic nucleus predominantly connects with the prefrontal cortex, the adjacent intralaminar nuclei connect with fronto-parietal cortex, and the midline thalamic nuclei connect with medial prefrontal cortex and medial temporal lobe. Taking into account this connectivity pattern, it is not surprising that the intralaminar and medial thalamus has been implicated in a variety of cognitive functions, including memory processing, attention and orienting, as well as reward-based behavior. This review addresses how the intralaminar and medial thalamus may regulate information transmission in cortical circuits. A key neural mechanism may involve intralaminar and medial thalamic neurons modulating the degree of synchrony between different groups of cortical neurons according to behavioral demands. Such a thalamic-mediated synchronization mechanism may give rise to large-scale integration of information across multiple cortical circuits, consequently influencing the level of arousal and consciousness. Overall, the growing evidence supports a general role for the higher-order thalamus in the control of cortical information transmission and cognitive processing.

  16. Cortical Activation during Action Observation, Action Execution, and Interpersonal Synchrony in Adults: A functional Near-Infrared Spectroscopy (fNIRS Study

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    Anjana N. Bhat

    2017-09-01

    Full Text Available Introduction: Humans engage in Interpersonal Synchrony (IPS as they synchronize their own actions with that of a social partner over time. When humans engage in imitation/IPS behaviors, multiple regions in the frontal, temporal, and parietal cortices are activated including the putative Mirror Neuron Systems (Iacoboni, 2005; Buxbaum et al., 2014. In the present study, we compared fNIRS-based cortical activation patterns across three conditions of action observation (“Watch” partner, action execution (“Do” on your own, and IPS (move “Together”.Methods: Fifteen typically developing adults completed a reach and cleanup task with the right arm while cortical activation was examined using a 24-channel, Hitachi fNIRS system. Each adult completed 8 trials across three conditions (Watch, Do, and Together. For each fNIRS channel, we obtained oxy hemoglobin (HbO2 and deoxy hemoglobin (HHb profiles. Spatial registration methods were applied to localize the cortical regions underneath each channel and to define six regions of interest (ROIs, right and left supero-anterior (SA or pre/post-central gyri, infero-posterior (IP or angular/supramarginal gyri, and infero-anterior (IA or superior/middle temporal gyri regions.Results: In terms of task-related differences, the majority of the ROIs were more active during Do and Together compared to Watch. Only the right/ipsilateral fronto-parietal and inferior parietal cortices had greater activation during Together compared to Do.Conclusions: The similarities in cortical activation between action execution and IPS suggest that neural control of IPS is more similar to its execution than observational aspects. To be clear, the more complex the actions performed, the more difficult the IPS behaviors. Secondly, IPS behaviors required slightly more right-sided activation (vs. execution/observation suggesting that IPS is a higher-order process involving more bilateral activation compared to its sub

  17. Dense neuron clustering explains connectivity statistics in cortical microcircuits.

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    Vladimir V Klinshov

    Full Text Available Local cortical circuits appear highly non-random, but the underlying connectivity rule remains elusive. Here, we analyze experimental data observed in layer 5 of rat neocortex and suggest a model for connectivity from which emerge essential observed non-random features of both wiring and weighting. These features include lognormal distributions of synaptic connection strength, anatomical clustering, and strong correlations between clustering and connection strength. Our model predicts that cortical microcircuits contain large groups of densely connected neurons which we call clusters. We show that such a cluster contains about one fifth of all excitatory neurons of a circuit which are very densely connected with stronger than average synapses. We demonstrate that such clustering plays an important role in the network dynamics, namely, it creates bistable neural spiking in small cortical circuits. Furthermore, introducing local clustering in large-scale networks leads to the emergence of various patterns of persistent local activity in an ongoing network activity. Thus, our results may bridge a gap between anatomical structure and persistent activity observed during working memory and other cognitive processes.

  18. Spatial integration and cortical dynamics.

    Science.gov (United States)

    Gilbert, C D; Das, A; Ito, M; Kapadia, M; Westheimer, G

    1996-01-23

    Cells in adult primary visual cortex are capable of integrating information over much larger portions of the visual field than was originally thought. Moreover, their receptive field properties can be altered by the context within which local features are presented and by changes in visual experience. The substrate for both spatial integration and cortical plasticity is likely to be found in a plexus of long-range horizontal connections, formed by cortical pyramidal cells, which link cells within each cortical area over distances of 6-8 mm. The relationship between horizontal connections and cortical functional architecture suggests a role in visual segmentation and spatial integration. The distribution of lateral interactions within striate cortex was visualized with optical recording, and their functional consequences were explored by using comparable stimuli in human psychophysical experiments and in recordings from alert monkeys. They may represent the substrate for perceptual phenomena such as illusory contours, surface fill-in, and contour saliency. The dynamic nature of receptive field properties and cortical architecture has been seen over time scales ranging from seconds to months. One can induce a remapping of the topography of visual cortex by making focal binocular retinal lesions. Shorter-term plasticity of cortical receptive fields was observed following brief periods of visual stimulation. The mechanisms involved entailed, for the short-term changes, altering the effectiveness of existing cortical connections, and for the long-term changes, sprouting of axon collaterals and synaptogenesis. The mutability of cortical function implies a continual process of calibration and normalization of the perception of visual attributes that is dependent on sensory experience throughout adulthood and might further represent the mechanism of perceptual learning.

  19. Learning in AN Oscillatory Cortical Model

    Science.gov (United States)

    Scarpetta, Silvia; Li, Zhaoping; Hertz, John

    We study a model of generalized-Hebbian learning in asymmetric oscillatory neural networks modeling cortical areas such as hippocampus and olfactory cortex. The learning rule is based on the synaptic plasticity observed experimentally, in particular long-term potentiation and long-term depression of the synaptic efficacies depending on the relative timing of the pre- and postsynaptic activities during learning. The learned memory or representational states can be encoded by both the amplitude and the phase patterns of the oscillating neural populations, enabling more efficient and robust information coding than in conventional models of associative memory or input representation. Depending on the class of nonlinearity of the activation function, the model can function as an associative memory for oscillatory patterns (nonlinearity of class II) or can generalize from or interpolate between the learned states, appropriate for the function of input representation (nonlinearity of class I). In the former case, simulations of the model exhibits a first order transition between the "disordered state" and the "ordered" memory state.

  20. Gender effects and sexual-orientation impact on androstadienone-evoked behavior and neural processing

    Directory of Open Access Journals (Sweden)

    Jacqueline eKrajnik

    2014-07-01

    Full Text Available In humans, the most established and investigated substance acting as a chemosignal, i.e., a substance that is excreted from the body, is 4,16-androstadien-3-one (AND. AND, which is found in sweat and saliva, is known to be responsible for influencing several variables, such as psychophysiological status, behavior, as well as cortical processing. The aim of the present review is to give insight into the variety of AND effects, with special regard to specific cross-sexual characteristics of this putative human chemosignal, emphasizing the neural activation patterns and factors such as contextual conditions. This review highlights the importance of including those contributing factors into the analysis of behavioral as well as brain-related studies.

  1. Markers of Pluripotency in Human Amniotic Epithelial Cells and Their Differentiation to Progenitor of Cortical Neurons

    Science.gov (United States)

    García-Castro, Irma Lydia; García-López, Guadalupe; Ávila-González, Daniela; Flores-Herrera, Héctor; Molina-Hernández, Anayansi; Portillo, Wendy; Ramón-Gallegos, Eva; Díaz, Néstor Fabián

    2015-01-01

    Human pluripotent stem cells (hPSC) have promise for regenerative medicine due to their auto-renovation and differentiation capacities. Nevertheless, there are several ethical and methodological issues about these cells that have not been resolved. Human amniotic epithelial cells (hAEC) have been proposed as source of pluripotent stem cells. Several groups have studied hAEC but have reported inconsistencies about their pluripotency properties. The aim of the present study was the in vitro characterization of hAEC collected from a Mexican population in order to identify transcription factors involved in the pluripotency circuitry and to determine their epigenetic state. Finally, we evaluated if these cells differentiate to cortical progenitors. We analyzed qualitatively and quantitatively the expression of the transcription factors of pluripotency (OCT4, SOX2, NANOG, KLF4 and REX1) by RT-PCR and RT-qPCR in hAEC. Also, we determined the presence of OCT4, SOX2, NANOG, SSEA3, SSEA4, TRA-1-60, E-cadherin, KLF4, TFE3 as well as the proliferation and epigenetic state by immunocytochemistry of the cells. Finally, hAEC were differentiated towards cortical progenitors using a protocol of two stages. Here we show that hAEC, obtained from a Mexican population and cultured in vitro (P0-P3), maintained the expression of several markers strongly involved in pluripotency maintenance (OCT4, SOX2, NANOG, TFE3, KLF4, SSEA3, SSEA4, TRA-1-60 and E-cadherin). Finally, when hAEC were treated with growth factors and small molecules, they expressed markers characteristic of cortical progenitors (TBR2, OTX2, NeuN and β-III-tubulin). Our results demonstrated that hAEC express naïve pluripotent markers (KLF4, REX1 and TFE3) as well as the cortical neuron phenotype after differentiation. This highlights the need for further investigation of hAEC as a possible source of hPSC. PMID:26720151

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

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    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.

  3. Recapitulating cortical development with organoid culture in vitro and modeling abnormal spindle-like (ASPM related primary) microcephaly disease

    Institute of Scientific and Technical Information of China (English)

    Rui Li; Le Sun; Ai Fang; Peng Li; Qian Wu; Xiaoqun Wang

    2017-01-01

    The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex.Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases.Several previous efforts have shown to grow neural organoid in culture dishes successfully,however we demonstrate a new paradigm that recapitulates neocortical development process with VZ,OSVZ formation and the lamination organization of cortical layer structure.In addition,using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient,we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids,suggesting a new strategy to study human developmental diseases in central nerve system.

  4. Right-frontal cortical asymmetry predicts increased proneness to nostalgia.

    Science.gov (United States)

    Tullett, Alexa M; Wildschut, Tim; Sedikides, Constantine; Inzlicht, Michael

    2015-08-01

    Nostalgia is often triggered by feelings-such as sadness, loneliness, or meaninglessness-that are typically associated with withdrawal motivation. Here, we examined whether a trait tendency to experience withdrawal motivation is associated with nostalgia proneness. Past work indicates that baseline right-frontal cortical asymmetry is a neural correlate of withdrawal-related motivation. We therefore hypothesized that higher baseline levels of right-frontal asymmetry would predict increased proneness to nostalgia. We assessed participants' baseline levels of frontal cortical activity using EEG. Results supported the hypothesis and demonstrated that the association between relative right-frontal asymmetry and increased nostalgia remained significant when controlling for the Big Five personality traits. Overall, these findings indicate that individuals with a stronger dispositional tendency to experience withdrawal-related motivation are more prone to nostalgia. © 2015 Society for Psychophysiological Research.

  5. Neural Correlates of Attitude Change Following Positive and Negative Advertisements

    Science.gov (United States)

    Kato, Junko; Ide, Hiroko; Kabashima, Ikuo; Kadota, Hiroshi; Takano, Kouji; Kansaku, Kenji

    2009-01-01

    Understanding changes in attitudes towards others is critical to understanding human behaviour. Neuropolitical studies have found that the activation of emotion-related areas in the brain is linked to resilient political preferences, and neuroeconomic research has analysed the neural correlates of social preferences that favour or oppose consideration of intrinsic rewards. This study aims to identify the neural correlates in the prefrontal cortices of changes in political attitudes toward others that are linked to social cognition. Functional magnetic resonance imaging (fMRI) experiments have presented videos from previous electoral campaigns and television commercials for major cola brands and then used the subjects' self-rated affinity toward political candidates as behavioural indicators. After viewing negative campaign videos, subjects showing stronger fMRI activation in the dorsolateral prefrontal cortex lowered their ratings of the candidate they originally supported more than did those with smaller fMRI signal changes in the same region. Subjects showing stronger activation in the medial prefrontal cortex tended to increase their ratings more than did those with less activation. The same regions were not activated by viewing negative advertisements for cola. Correlations between the self-rated values and the neural signal changes underscore the metric representation of observed decisions (i.e., whether to support or not) in the brain. This indicates that neurometric analysis may contribute to the exploration of the neural correlates of daily social behaviour. PMID:19503749

  6. Organization of Anti-Phase Synchronization Pattern in Neural Networks: What are the Key Factors?

    Science.gov (United States)

    Li, Dong; Zhou, Changsong

    2011-01-01

    Anti-phase oscillation has been widely observed in cortical neural network. Elucidating the mechanism underlying the organization of anti-phase pattern is of significance for better understanding more complicated pattern formations in brain networks. In dynamical systems theory, the organization of anti-phase oscillation pattern has usually been considered to relate to time delay in coupling. This is consistent to conduction delays in real neural networks in the brain due to finite propagation velocity of action potentials. However, other structural factors in cortical neural network, such as modular organization (connection density) and the coupling types (excitatory or inhibitory), could also play an important role. In this work, we investigate the anti-phase oscillation pattern organized on a two-module network of either neuronal cell model or neural mass model, and analyze the impact of the conduction delay times, the connection densities, and coupling types. Our results show that delay times and coupling types can play key roles in this organization. The connection densities may have an influence on the stability if an anti-phase pattern exists due to the other factors. Furthermore, we show that anti-phase synchronization of slow oscillations can be achieved with small delay times if there is interaction between slow and fast oscillations. These results are significant for further understanding more realistic spatiotemporal dynamics of cortico-cortical communications. PMID:22232576

  7. The Complexity of Dynamics in Small Neural Circuits.

    Directory of Open Access Journals (Sweden)

    Diego Fasoli

    2016-08-01

    Full Text Available Mean-field approximations are a powerful tool for studying large neural networks. However, they do not describe well the behavior of networks composed of a small number of neurons. In this case, major differences between the mean-field approximation and the real behavior of the network can arise. Yet, many interesting problems in neuroscience involve the study of mesoscopic networks composed of a few tens of neurons. Nonetheless, mathematical methods that correctly describe networks of small size are still rare, and this prevents us to make progress in understanding neural dynamics at these intermediate scales. Here we develop a novel systematic analysis of the dynamics of arbitrarily small networks composed of homogeneous populations of excitatory and inhibitory firing-rate neurons. We study the local bifurcations of their neural activity with an approach that is largely analytically tractable, and we numerically determine the global bifurcations. We find that for strong inhibition these networks give rise to very complex dynamics, caused by the formation of multiple branching solutions of the neural dynamics equations that emerge through spontaneous symmetry-breaking. This qualitative change of the neural dynamics is a finite-size effect of the network, that reveals qualitative and previously unexplored differences between mesoscopic cortical circuits and their mean-field approximation. The most important consequence of spontaneous symmetry-breaking is the ability of mesoscopic networks to regulate their degree of functional heterogeneity, which is thought to help reducing the detrimental effect of noise correlations on cortical information processing.

  8. State-dependent, bidirectional modulation of neural network activity by endocannabinoids.

    Science.gov (United States)

    Piet, Richard; Garenne, André; Farrugia, Fanny; Le Masson, Gwendal; Marsicano, Giovanni; Chavis, Pascale; Manzoni, Olivier J

    2011-11-16

    The endocannabinoid (eCB) system and the cannabinoid CB1 receptor (CB1R) play key roles in the modulation of brain functions. Although actions of eCBs and CB1Rs are well described at the synaptic level, little is known of their modulation of neural activity at the network level. Using microelectrode arrays, we have examined the role of CB1R activation in the modulation of the electrical activity of rat and mice cortical neural networks in vitro. We find that exogenous activation of CB1Rs expressed on glutamatergic neurons decreases the spontaneous activity of cortical neural networks. Moreover, we observe that the net effect of the CB1R antagonist AM251 inversely correlates with the initial level of activity in the network: blocking CB1Rs increases network activity when basal network activity is low, whereas it depresses spontaneous activity when its initial level is high. Our results reveal a complex role of CB1Rs in shaping spontaneous network activity, and suggest that the outcome of endogenous neuromodulation on network function might be state dependent.

  9. Neural Global Pattern Similarity Underlies True and False Memories.

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    Ye, Zhifang; Zhu, Bi; Zhuang, Liping; Lu, Zhonglin; Chen, Chuansheng; Xue, Gui

    2016-06-22

    The neural processes giving rise to human memory strength signals remain poorly understood. Inspired by formal computational models that posit a central role of global matching in memory strength, we tested a novel hypothesis that the strengths of both true and false memories arise from the global similarity of an item's neural activation pattern during retrieval to that of all the studied items during encoding (i.e., the encoding-retrieval neural global pattern similarity [ER-nGPS]). We revealed multiple ER-nGPS signals that carried distinct information and contributed differentially to true and false memories: Whereas the ER-nGPS in the parietal regions reflected semantic similarity and was scaled with the recognition strengths of both true and false memories, ER-nGPS in the visual cortex contributed solely to true memory. Moreover, ER-nGPS differences between the parietal and visual cortices were correlated with frontal monitoring processes. By combining computational and neuroimaging approaches, our results advance a mechanistic understanding of memory strength in recognition. What neural processes give rise to memory strength signals, and lead to our conscious feelings of familiarity? Using fMRI, we found that the memory strength of a given item depends not only on how it was encoded during learning, but also on the similarity of its neural representation with other studied items. The global neural matching signal, mainly in the parietal lobule, could account for the memory strengths of both studied and unstudied items. Interestingly, a different global matching signal, originated from the visual cortex, could distinguish true from false memories. The findings reveal multiple neural mechanisms underlying the memory strengths of events registered in the brain. Copyright © 2016 the authors 0270-6474/16/366792-11$15.00/0.

  10. Periventricular Heterotopia: Shuttling of Proteins through Vesicles and Actin in Cortical Development and Disease

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    Volney L. Sheen

    2012-01-01

    Full Text Available During cortical development, proliferating neural progenitors exhibit polarized apical and basolateral membranes that are maintained by tightly controlled and membrane-specific vesicular trafficking pathways. Disruption of polarity through impaired delivery of proteins can alter cell fate decisions and consequent expansion of the progenitor pool, as well as impact the integrity of the neuroependymal lining. Loss of neuroependymal integrity disrupts radial glial scaffolding and alters initial neuronal migration from the ventricular zone. Vesicle trafficking is also required for maintenance of lipid and protein cycling within the leading and trailing edge of migratory neurons, as well as dendrites and synapses of mature neurons. Defects in this transport machinery disrupt neuronal identity, migration, and connectivity and give rise to a malformation of cortical development termed as periventricular heterotopia (PH. PH is characterized by a reduction in brain size, ectopic clusters of neurons localized along the lateral ventricle, and epilepsy and dyslexia. These anatomical anomalies correlate with developmental impairments in neural progenitor proliferation and specification, migration from loss of neuroependymal integrity and neuronal motility, and aberrant neuronal process extension. Genes causal for PH regulate vesicle-mediated endocytosis along an actin cytoskeletal network. This paper explores the role of these dynamic processes in cortical development and disease.

  11. Hierarchical graphical-based human pose estimation via local multi-resolution convolutional neural network

    Science.gov (United States)

    Zhu, Aichun; Wang, Tian; Snoussi, Hichem

    2018-03-01

    This paper addresses the problems of the graphical-based human pose estimation in still images, including the diversity of appearances and confounding background clutter. We present a new architecture for estimating human pose using a Convolutional Neural Network (CNN). Firstly, a Relative Mixture Deformable Model (RMDM) is defined by each pair of connected parts to compute the relative spatial information in the graphical model. Secondly, a Local Multi-Resolution Convolutional Neural Network (LMR-CNN) is proposed to train and learn the multi-scale representation of each body parts by combining different levels of part context. Thirdly, a LMR-CNN based hierarchical model is defined to explore the context information of limb parts. Finally, the experimental results demonstrate the effectiveness of the proposed deep learning approach for human pose estimation.

  12. Hierarchical graphical-based human pose estimation via local multi-resolution convolutional neural network

    Directory of Open Access Journals (Sweden)

    Aichun Zhu

    2018-03-01

    Full Text Available This paper addresses the problems of the graphical-based human pose estimation in still images, including the diversity of appearances and confounding background clutter. We present a new architecture for estimating human pose using a Convolutional Neural Network (CNN. Firstly, a Relative Mixture Deformable Model (RMDM is defined by each pair of connected parts to compute the relative spatial information in the graphical model. Secondly, a Local Multi-Resolution Convolutional Neural Network (LMR-CNN is proposed to train and learn the multi-scale representation of each body parts by combining different levels of part context. Thirdly, a LMR-CNN based hierarchical model is defined to explore the context information of limb parts. Finally, the experimental results demonstrate the effectiveness of the proposed deep learning approach for human pose estimation.

  13. Spike-timing-dependent plasticity in the human dorso-lateral prefrontal cortex.

    Science.gov (United States)

    Casula, Elias Paolo; Pellicciari, Maria Concetta; Picazio, Silvia; Caltagirone, Carlo; Koch, Giacomo

    2016-12-01

    Changes in the synaptic strength of neural connections are induced by repeated coupling of activity of interconnected neurons with precise timing, a phenomenon known as spike-timing-dependent plasticity (STDP). It is debated if this mechanism exists in large-scale cortical networks in humans. We combined transcranial magnetic stimulation (TMS) with concurrent electroencephalography (EEG) to directly investigate the effects of two paired associative stimulation (PAS) protocols (fronto-parietal and parieto-frontal) of pre and post-synaptic inputs within the human fronto-parietal network. We found evidence that the dorsolateral prefrontal cortex (DLPFC) has the potential to form robust STDP. Long-term potentiation/depression of TMS-evoked cortical activity is prompted after that DLPFC stimulation is followed/preceded by posterior parietal stimulation. Such bidirectional changes are paralleled by sustained increase/decrease of high-frequency oscillatory activity, likely reflecting STDP responsivity. The current findings could be important to drive plasticity of damaged cortical circuits in patients with cognitive or psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. In vitro differentiation of neural cells from human adipose tissue derived stromal cells.

    Science.gov (United States)

    Dave, Shruti D; Patel, Chetan N; Vanikar, Aruna V; Trivedi, Hargovind L

    2018-01-01

    Stem cells, including neural stem cells (NSCs), are endowed with self-renewal capability and hence hold great opportunity for the institution of replacement/protective therapy. We propose a method for in vitro generation of stromal cells from human adipose tissue and their differentiation into neural cells. Ten grams of donor adipose tissue was surgically resected from the abdominal wall of the human donor after the participants' informed consents. The resected adipose tissue was minced and incubated for 1 hour in the presence of an enzyme (collagenase-type I) at 37 0 C followed by its centrifugation. After centrifugation, the supernatant and pellets were separated and cultured in a medium for proliferation at 37 0 C with 5% CO2 for 9-10 days in separate tissue culture dishes for generation of mesenchymal stromal cells (MSC). At the end of the culture, MSC were harvested and analyzed. The harvested MSC were subjected for further culture for their differentiation into neural cells for 5-7 days using differentiation medium mainly comprising of neurobasal medium. At the end of the procedure, culture cells were isolated and studied for expression of transcriptional factor proteins: orthodenticle homolog-2 (OTX-2), beta-III-tubulin (β3-Tubulin), glial-fibrillary acid protein (GFAP) and synaptophysin-β2. In total, 50 neural cells-lines were generated. In vitro generated MSC differentiated neural cells' mean quantum was 5.4 ± 6.9 ml with the mean cell count being, 5.27 ± 2.65 × 10 3/ μl. All of them showed the presence of OTX-2, β3-Tubulin, GFAP, synaptophysin-β2. Neural cells can be differentiated in vitro from MSC safely and effectively. In vitro generated neural cells represent a potential therapy for recovery from spinal cord injuries and neurodegenerative disease.

  15. Neural Integration of Information Specifying Human Structure from Form, Motion, and Depth

    Science.gov (United States)

    Jackson, Stuart; Blake, Randolph

    2010-01-01

    Recent computational models of biological motion perception operate on ambiguous two-dimensional representations of the body (e.g., snapshots, posture templates) and contain no explicit means for disambiguating the three-dimensional orientation of a perceived human figure. Are there neural mechanisms in the visual system that represent a moving human figure’s orientation in three dimensions? To isolate and characterize the neural mechanisms mediating perception of biological motion, we used an adaptation paradigm together with bistable point-light (PL) animations whose perceived direction of heading fluctuates over time. After exposure to a PL walker with a particular stereoscopically defined heading direction, observers experienced a consistent aftereffect: a bistable PL walker, which could be perceived in the adapted orientation or reversed in depth, was perceived predominantly reversed in depth. A phase-scrambled adaptor produced no aftereffect, yet when adapting and test walkers differed in size or appeared on opposite sides of fixation aftereffects did occur. Thus, this heading direction aftereffect cannot be explained by local, disparity-specific motion adaptation, and the properties of scale and position invariance imply higher-level origins of neural adaptation. Nor is disparity essential for producing adaptation: when suspended on top of a stereoscopically defined, rotating globe, a context-disambiguated “globetrotter” was sufficient to bias the bistable walker’s direction, as were full-body adaptors. In sum, these results imply that the neural signals supporting biomotion perception integrate information on the form, motion, and three-dimensional depth orientation of the moving human figure. Models of biomotion perception should incorporate mechanisms to disambiguate depth ambiguities in two-dimensional body representations. PMID:20089892

  16. Prior Knowledge about Objects Determines Neural Color Representation in Human Visual Cortex.

    Science.gov (United States)

    Vandenbroucke, A R E; Fahrenfort, J J; Meuwese, J D I; Scholte, H S; Lamme, V A F

    2016-04-01

    To create subjective experience, our brain must translate physical stimulus input by incorporating prior knowledge and expectations. For example, we perceive color and not wavelength information, and this in part depends on our past experience with colored objects ( Hansen et al. 2006; Mitterer and de Ruiter 2008). Here, we investigated the influence of object knowledge on the neural substrates underlying subjective color vision. In a functional magnetic resonance imaging experiment, human subjects viewed a color that lay midway between red and green (ambiguous with respect to its distance from red and green) presented on either typical red (e.g., tomato), typical green (e.g., clover), or semantically meaningless (nonsense) objects. Using decoding techniques, we could predict whether subjects viewed the ambiguous color on typical red or typical green objects based on the neural response of veridical red and green. This shift of neural response for the ambiguous color did not occur for nonsense objects. The modulation of neural responses was observed in visual areas (V3, V4, VO1, lateral occipital complex) involved in color and object processing, as well as frontal areas. This demonstrates that object memory influences wavelength information relatively early in the human visual system to produce subjective color vision. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. CD133 (Prominin negative human neural stem cells are clonogenic and tripotent.

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    Yirui Sun

    Full Text Available CD133 (Prominin is widely used as a marker for the identification and isolation of neural precursor cells from normal brain or tumor tissue. However, the assumption that CD133 is expressed constitutively in neural precursor cells has not been examined.In this study, we demonstrate that CD133 and a second marker CD15 are expressed heterogeneously in uniformly undifferentiated human neural stem (NS cell cultures. After fractionation by flow cytometry, clonogenic tripotent cells are found in populations negative or positive for either marker. We further show that CD133 is down-regulated at the mRNA level in cells lacking CD133 immunoreactivity. Cell cycle profiling reveals that CD133 negative cells largely reside in G1/G0, while CD133 positive cells are predominantly in S, G2, or M phase. A similar pattern is apparent in mouse NS cell lines. Compared to mouse NS cells, however, human NS cell cultures harbour an increased proportion of CD133 negative cells and display a longer doubling time. This may in part reflect a sub-population of slow- or non-cycling cells amongst human NS cells because we find that around 5% of cells do not take up BrdU over a 14-day labelling period. Non-proliferating NS cells remain undifferentiated and at least some of them are capable of re-entry into the cell cycle and subsequent continuous expansion.The finding that a significant fraction of clonogenic neural stem cells lack the established markers CD133 and CD15, and that some of these cells may be dormant or slow-cycling, has implications for approaches to identify and isolate neural stem cells and brain cancer stem cells. Our data also suggest the possibility that CD133 may be specifically down-regulated during G0/G1, and this should be considered when this marker is used to identify and isolate other tissue and cancer stem cells.

  18. Efficient and Fast Differentiation of Human Neural Stem Cells from Human Embryonic Stem Cells for Cell Therapy

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    Xinxin Han

    2017-01-01

    Full Text Available Stem cell-based therapies have been used for repairing damaged brain tissue and helping functional recovery after brain injury. Aberrance neurogenesis is related with brain injury, and multipotential neural stem cells from human embryonic stem (hES cells provide a great promise for cell replacement therapies. Optimized protocols for neural differentiation are necessary to produce functional human neural stem cells (hNSCs for cell therapy. However, the qualified procedure is scarce and detailed features of hNSCs originated from hES cells are still unclear. In this study, we developed a method to obtain hNSCs from hES cells, by which we could harvest abundant hNSCs in a relatively short time. Then, we examined the expression of pluripotent and multipotent marker genes through immunostaining and confirmed differentiation potential of the differentiated hNSCs. Furthermore, we analyzed the mitotic activity of these hNSCs. In this report, we provided comprehensive features of hNSCs and delivered the knowledge about how to obtain more high-quality hNSCs from hES cells which may help to accelerate the NSC-based therapies in brain injury treatment.

  19. Neural sources of visual working memory maintenance in human parietal and ventral extrastriate visual cortex.

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    Becke, Andreas; Müller, Notger; Vellage, Anne; Schoenfeld, Mircea Ariel; Hopf, Jens-Max

    2015-04-15

    Maintaining information in visual working memory is reliably indexed by the contralateral delay activity (CDA) - a sustained modulation of the event-related potential (ERP) with a topographical maximum over posterior scalp regions contralateral to the memorized input. Based on scalp topography, it is hypothesized that the CDA reflects neural activity in the parietal cortex, but the precise cortical origin of underlying electric activity was never determined. Here we combine ERP recordings with magnetoencephalography based source localization to characterize the cortical current sources generating the CDA. Observers performed a cued delayed match to sample task where either the color or the relative position of colored dots had to be maintained in memory. A detailed source-localization analysis of the magnetic activity in the retention interval revealed that the magnetic analog of the CDA (mCDA) is generated by current sources in the parietal cortex. Importantly, we find that the mCDA also receives contribution from current sources in the ventral extrastriate cortex that display a time-course similar to the parietal sources. On the basis of the magnetic responses, forward modeling of ERP data reveals that the ventral sources have non-optimal projections and that these sources are therefore concealed in the ERP by overlapping fields with parietal projections. The present observations indicate that visual working memory maintenance, as indexed by the CDA, involves the parietal cortical regions as well as the ventral extrastriate regions, which code the sensory representation of the memorized content. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Characterization of energy and neurotransmitter metabolism in cortical glutamatergic neurons derived from human induced pluripotent stem cells: A novel approach to study metabolism in human neurons.

    Science.gov (United States)

    Aldana, Blanca I; Zhang, Yu; Lihme, Maria Fog; Bak, Lasse K; Nielsen, Jørgen E; Holst, Bjørn; Hyttel, Poul; Freude, Kristine K; Waagepetersen, Helle S

    2017-06-01

    Alterations in the cellular metabolic machinery of the brain are associated with neurodegenerative disorders such as Alzheimer's disease. Novel human cellular disease models are essential in order to study underlying disease mechanisms. In the present study, we characterized major metabolic pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U- 13 C]glucose, [U- 13 C]glutamate or [U- 13 C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass spectrometry, and cellular amino acid content was quantified by high-performance liquid chromatography. Additionally, we evaluated mitochondrial function using real-time assessment of oxygen consumption via the Seahorse XF e 96 Analyzer. Moreover, in order to validate the hiPSC-derived neurons as a model system, a metabolic profiling was performed in parallel in primary neuronal cultures of mouse cerebral cortex and cerebellum. These serve as well-established models of GABAergic and glutamatergic neurons, respectively. The hiPSC-derived neurons were previously characterized as being forebrain-specific cortical glutamatergic neurons. However, a comparable preparation of predominantly mouse cortical glutamatergic neurons is not available. We found a higher glycolytic capacity in hiPSC-derived neurons compared to mouse neurons and a substantial oxidative metabolism through the mitochondrial tricarboxylic acid (TCA) cycle. This finding is supported by the extracellular acidification and oxygen consumption rates measured in the cultured human neurons. [U- 13 C]Glutamate and [U- 13 C]glutamine were found to be efficient energy substrates for the neuronal cultures originating from both mice and humans. Interestingly, isotopic labeling in metabolites from [U- 13 C]glutamate was higher than that from [U- 13 C]glutamine. Although the metabolic profile of hiPSC-derived neurons in vitro was

  1. Regulator of G protein signaling 5 (RGS5) inhibits sonic hedgehog function in mouse cortical neurons.

    Science.gov (United States)

    Liu, Chuanliang; Hu, Qiongqiong; Jing, Jia; Zhang, Yun; Jin, Jing; Zhang, Liulei; Mu, Lili; Liu, Yumei; Sun, Bo; Zhang, Tongshuai; Kong, Qingfei; Wang, Guangyou; Wang, Dandan; Zhang, Yao; Liu, Xijun; Zhao, Wei; Wang, Jinghua; Feng, Tao; Li, Hulun

    2017-09-01

    Regulator of G protein signaling 5 (RGS5) acts as a GTPase-activating protein (GAP) for the Gαi subunit and negatively regulates G protein-coupled receptor signaling. However, its presence and function in postmitotic differentiated primary neurons remains largely uncharacterized. During neural development, sonic hedgehog (Shh) signaling is involved in cell signaling pathways via Gαi activity. In particular, Shh signaling is essential for embryonic neural tube patterning, which has been implicated in neuronal polarization involving neurite outgrowth. Here, we examined whether RGS5 regulates Shh signaling in neurons. RGS5 transcripts were found to be expressed in cortical neurons and their expression gradually declined in a time-dependent manner in culture system. When an adenovirus expressing RGS5 was introduced into an in vitro cell culture model of cortical neurons, RGS5 overexpression significantly reduced neurite outgrowth and FM4-64 uptake, while cAMP-PKA signaling was also affected. These findings suggest that RGS5 inhibits Shh function during neurite outgrowth and the presynaptic terminals of primary cortical neurons mature via modulation of cAMP. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A cortical–hippocampal–cortical loop of information processing during memory consolidation

    Science.gov (United States)

    Rothschild, Gideon; Eban, Elad; Frank, Loren M

    2018-01-01

    Hippocampal replay during sharp-wave ripple events (SWRs) is thought to drive memory consolidation in hippocampal and cortical circuits. Changes in neocortical activity can precede SWR events, but whether and how these changes influence the content of replay remains unknown. Here we show that during sleep there is a rapid cortical–hippocampal–cortical loop of information flow around the times of SWRs. We recorded neural activity in auditory cortex (AC) and hippocampus of rats as they learned a sound-guided task and during sleep. We found that patterned activation in AC precedes and predicts the subsequent content of hippocampal activity during SWRs, while hippocampal patterns during SWRs predict subsequent AC activity. Delivering sounds during sleep biased AC activity patterns, and sound-biased AC patterns predicted subsequent hippocampal activity. These findings suggest that activation of specific cortical representations during sleep influences the identity of the memories that are consolidated into long-term stores. PMID:27941790

  3. Information flow between interacting human brains: Identification, validation, and relationship to social expertise.

    Science.gov (United States)

    Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

    2015-04-21

    Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender's and receiver's temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions.

  4. Neural Markers of Performance States in an Olympic Athlete: An EEG Case Study in Air-Pistol Shooting.

    Science.gov (United States)

    di Fronso, Selenia; Robazza, Claudio; Filho, Edson; Bortoli, Laura; Comani, Silvia; Bertollo, Maurizio

    2016-06-01

    This study focused on identifying the neural markers underlying optimal and suboptimal performance experiences of an elite air-pistol shooter, based on the tenets of the multi-action plan (MAP) model. According to the MAP model's assumptions, skilled athletes' cortical patterns are expected to differ among optimal/automatic (Type 1), optimal/controlled (Type 2), suboptimal/controlled (Type 3), and suboptimal/automatic (Type 4) performance experiences. We collected performance (target pistol shots), cognitive-affective (perceived control, accuracy, and hedonic tone), and cortical activity data (32-channel EEG) of an elite shooter. Idiosyncratic descriptive analyses revealed differences in perceived accuracy in regard to optimal and suboptimal performance states. Event-Related Desynchronization/Synchronization analysis supported the notion that optimal-automatic performance experiences (Type 1) were characterized by a global synchronization of cortical arousal associated with the shooting task, whereas suboptimal controlled states (Type 3) were underpinned by high cortical activity levels in the attentional brain network. Results are addressed in light of the neural efficiency hypothesis and reinvestment theory. Perceptual training recommendations aimed at restoring optimal performance levels are discussed. Key pointsWe investigated the neural markers underlying optimal and suboptimal performance experiences of an elite air-pistol shooter.Optimal/automatic performance is characterized by a global synchronization of cortical activity associated with the shooting task.Suboptimal controlled performance is characterized by high cortical arousal levels in the attentional brain networks.Focused Event Related Desynchronization activity during Type 1 performance in frontal midline theta was found, with a clear distribution of Event Related Synchronization in the frontal and central areas just prior to shot release.Event Related Desynchronization patterns in low Alpha band

  5. Glycation of human cortical and cancellous bone captures differences in the formation of Maillard reaction products between glucose and ribose.

    Directory of Open Access Journals (Sweden)

    Grażyna E Sroga

    Full Text Available To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs at the levels that corresponded to approx. 25-30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation or ribose (ribosylation. Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women. More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples. Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar

  6. Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells

    Science.gov (United States)

    Katsura, Mari; Cyou-Nakamine, Hiromasa; Zen, Qin; Zen, Yang; Nansai, Hiroko; Amagasa, Shota; Kanki, Yasuharu; Inoue, Tsuyoshi; Kaneki, Kiyomi; Taguchi, Akashi; Kobayashi, Mika; Kaji, Toshiyuki; Kodama, Tatsuhiko; Miyagawa, Kiyoshi; Wada, Youichiro; Akimitsu, Nobuyoshi; Sone, Hideko

    2016-01-01

    The effects of chronic low-dose radiation on human health have not been well established. Recent studies have revealed that neural progenitor cells are present not only in the fetal brain but also in the adult brain. Since immature cells are generally more radiosensitive, here we investigated the effects of chronic low-dose radiation on cultured human neural progenitor cells (hNPCs) derived from embryonic stem cells. Radiation at low doses of 31, 124 and 496 mGy per 72 h was administered to hNPCs. The effects were estimated by gene expression profiling with microarray analysis as well as morphological analysis. Gene expression was dose-dependently changed by radiation. By thirty-one mGy of radiation, inflammatory pathways involving interferon signaling and cell junctions were altered. DNA repair and cell adhesion molecules were affected by 124 mGy of radiation while DNA synthesis, apoptosis, metabolism, and neural differentiation were all affected by 496 mGy of radiation. These in vitro results suggest that 496 mGy radiation affects the development of neuronal progenitor cells while altered gene expression was observed at a radiation dose lower than 100 mGy. This study would contribute to the elucidation of the clinical and subclinical phenotypes of impaired neuronal development induced by chronic low-dose radiation.

  7. Neural mechanisms of selective attention in the somatosensory system.

    Science.gov (United States)

    Gomez-Ramirez, Manuel; Hysaj, Kristjana; Niebur, Ernst

    2016-09-01

    Selective attention allows organisms to extract behaviorally relevant information while ignoring distracting stimuli that compete for the limited resources of their central nervous systems. Attention is highly flexible, and it can be harnessed to select information based on sensory modality, within-modality feature(s), spatial location, object identity, and/or temporal properties. In this review, we discuss the body of work devoted to understanding mechanisms of selective attention in the somatosensory system. In particular, we describe the effects of attention on tactile behavior and corresponding neural activity in somatosensory cortex. Our focus is on neural mechanisms that select tactile stimuli based on their location on the body (somatotopic-based attention) or their sensory feature (feature-based attention). We highlight parallels between selection mechanisms in touch and other sensory systems and discuss several putative neural coding schemes employed by cortical populations to signal the behavioral relevance of sensory inputs. Specifically, we contrast the advantages and disadvantages of using a gain vs. spike-spike correlation code for representing attended sensory stimuli. We favor a neural network model of tactile attention that is composed of frontal, parietal, and subcortical areas that controls somatosensory cells encoding the relevant stimulus features to enable preferential processing throughout the somatosensory hierarchy. Our review is based on data from noninvasive electrophysiological and imaging data in humans as well as single-unit recordings in nonhuman primates. Copyright © 2016 the American Physiological Society.

  8. Primary cortical folding in the human newborn: an early marker of later functional development

    Science.gov (United States)

    Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Ha-Vinh Leuchter, R.; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Hüppi, P. S.

    2008-01-01

    In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26–36 weeks of gestational age), and defined early ‘endophenotypes’ of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants’ outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB). PMID:18587151

  9. Cell reprogramming by 3D bioprinting of human fibroblasts in polyurethane hydrogel for fabrication of neural-like constructs.

    Science.gov (United States)

    Ho, Lin; Hsu, Shan-Hui

    2018-04-01

    3D bioprinting is a technique which enables the direct printing of biodegradable materials with cells into 3D tissue. So far there is no cell reprogramming in situ performed with the 3D bioprinting process. Forkhead box D3 (FoxD3) is a transcription factor and neural crest marker, which was reported to reprogram human fibroblasts into neural crest stem-like cells. In this study, we synthesized a new biodegradable thermo-responsive waterborne polyurethane (PU) gel as a bioink. FoxD3 plasmids and human fibroblasts were co-extruded with the PU hydrogel through the syringe needle tip for cell reprogramming. The rheological properties of the PU hydrogel including the modulus, gelation time, and shear thinning were optimized for the transfection effect of FoxD3 in situ. The corresponding shear rate and shear stress were examined. Results showed that human fibroblasts could be reprogrammed into neural crest stem-like cells with high cell viability during the extrusion process under an average shear stress ∼190 Pa. We further translated the method to the extrusion-based 3D bioprinting, and demonstrated that human fibroblasts co-printed with FoxD3 in the thermo-responsive PU hydrogel could be reprogrammed and differentiated into a neural-tissue like construct at 14 days after induction. The neural-like tissue construct produced by 3D bioprinting from human fibroblasts may be applied to personalized drug screening or neuroregeneration. There is no study so far on cell reprogramming in situ with 3D bioprinting. In this manuscript, a new thermoresponsive polyurethane bioink was developed and employed to deliver FoxD3 plasmid into human fibroblasts by the extrusion-based bioprinting. When the polyurethane gel was extruded through the syringe tip, the shear stress generated may have caused the transient membrane permeability for transfection. The shear stress was optimized for transfection in situ by 3D bioprinting. We demonstrated that human fibroblasts could be

  10. High Definition Transcranial Direct Current Stimulation Induces Both Acute and Persistent Changes in Broadband Cortical Synchronization: a Simultaneous tDCS-EEG Study

    Science.gov (United States)

    Roy, Abhrajeet; Baxter, Bryan

    2014-01-01

    The goal of this study was to develop methods for simultaneously acquiring electrophysiological data during high definition transcranial direct current stimulation (tDCS) using high resolution electroencephalography (EEG). Previous studies have pointed to the after effects of tDCS on both motor and cognitive performance, and there appears to be potential for using tDCS in a variety of clinical applications. However, little is known about the real-time effects of tDCS on rhythmic cortical activity in humans due to the technical challenges of simultaneously obtaining electrophysiological data during ongoing stimulation. Furthermore, the mechanisms of action of tDCS in humans are not well understood. We have conducted a simultaneous tDCS-EEG study in a group of healthy human subjects. Significant acute and persistent changes in spontaneous neural activity and event related synchronization (ERS) were observed during and after the application of high definition tDCS over the left sensorimotor cortex. Both anodal and cathodal stimulation resulted in acute global changes in broadband cortical activity which were significantly different than the changes observed in response to sham stimulation. For the group of 8 subjects studied, broadband individual changes in spontaneous activity during stimulation were apparent both locally and globally. In addition, we found that high definition tDCS of the left sensorimotor cortex can induce significant ipsilateral and contralateral changes in event related desynchronization (ERD) and ERS during motor imagination following the end of the stimulation period. Overall, our results demonstrate the feasibility of acquiring high resolution EEG during high definition tDCS and provide evidence that tDCS in humans directly modulates rhythmic cortical synchronization during and after its administration. PMID:24956615

  11. Generation of Regionally Specified Neural Progenitors and Functional Neurons from Human Embryonic Stem Cells under Defined Conditions

    Directory of Open Access Journals (Sweden)

    Agnete Kirkeby

    2012-06-01

    Full Text Available To model human neural-cell-fate specification and to provide cells for regenerative therapies, we have developed a method to generate human neural progenitors and neurons from human embryonic stem cells, which recapitulates human fetal brain development. Through the addition of a small molecule that activates canonical WNT signaling, we induced rapid and efficient dose-dependent specification of regionally defined neural progenitors ranging from telencephalic forebrain to posterior hindbrain fates. Ten days after initiation of differentiation, the progenitors could be transplanted to the adult rat striatum, where they formed neuron-rich and tumor-free grafts with maintained regional specification. Cells patterned toward a ventral midbrain (VM identity generated a high proportion of authentic dopaminergic neurons after transplantation. The dopamine neurons showed morphology, projection pattern, and protein expression identical to that of human fetal VM cells grafted in parallel. VM-patterned but not forebrain-patterned neurons released dopamine and reversed motor deficits in an animal model of Parkinson's disease.

  12. Neural mechanisms underlying melodic perception and memory for pitch.

    Science.gov (United States)

    Zatorre, R J; Evans, A C; Meyer, E

    1994-04-01

    The neural correlates of music perception were studied by measuring cerebral blood flow (CBF) changes with positron emission tomography (PET). Twelve volunteers were scanned using the bolus water method under four separate conditions: (1) listening to a sequence of noise bursts, (2) listening to unfamiliar tonal melodies, (3) comparing the pitch of the first two notes of the same set of melodies, and (4) comparing the pitch of the first and last notes of the melodies. The latter two conditions were designed to investigate short-term pitch retention under low or high memory load, respectively. Subtraction of the obtained PET images, superimposed on matched MRI scans, provides anatomical localization of CBF changes associated with specific cognitive functions. Listening to melodies, relative to acoustically matched noise sequences, resulted in CBF increases in the right superior temporal and right occipital cortices. Pitch judgments of the first two notes of each melody, relative to passive listening to the same stimuli, resulted in right frontal-lobe activation. Analysis of the high memory load condition relative to passive listening revealed the participation of a number of cortical and subcortical regions, notably in the right frontal and right temporal lobes, as well as in parietal and insular cortex. Both pitch judgment conditions also revealed CBF decreases within the left primary auditory cortex. We conclude that specialized neural systems in the right superior temporal cortex participate in perceptual analysis of melodies; pitch comparisons are effected via a neural network that includes right prefrontal cortex, but active retention of pitch involves the interaction of right temporal and frontal cortices.

  13. Neural modeling of prefrontal executive function

    Energy Technology Data Exchange (ETDEWEB)

    Levine, D.S. [Univ. of Texas, Arlington, TX (United States)

    1996-12-31

    Brain executive function is based in a distributed system whereby prefrontal cortex is interconnected with other cortical. and subcortical loci. Executive function is divided roughly into three interacting parts: affective guidance of responses; linkage among working memory representations; and forming complex behavioral schemata. Neural network models of each of these parts are reviewed and fit into a preliminary theoretical framework.

  14. Slow cortical potentials and "inner time consciousness" - A neuro-phenomenal hypothesis about the "width of present".

    Science.gov (United States)

    Northoff, Georg

    2016-05-01

    William James postulated a "stream of consciousness" that presupposes temporal continuity. The neuronal mechanisms underlying the construction of such temporal continuity remain unclear, however, in my contribution, I propose a neuro-phenomenal hypothesis that is based on slow cortical potentials and their extension of the present moment as described in the phenomenal term of "width of present". More specifically, I focus on the way the brain's neural activity needs to be encoded in order to make possible the "stream of consciousness." This leads us again to the low-frequency fluctuations of the brain's neural activity and more specifically to slow cortical potentials (SCPs). Due to their long phase duration as low-frequency fluctuations, SCPs can integrate different stimuli and their associated neural activity from different regions in one converging region. Such integration may be central for consciousness to occur, as it was recently postulated by He and Raichle. They leave open, however, the question of the exact neuronal mechanisms, like the encoding strategy, that make possible the association of the otherwise purely neuronal SCP with consciousness and its phenomenal features. I hypothesize that SCPs allow for linking and connecting different discrete points in physical time by encoding their statistically based temporal differences rather than the single discrete time points by themselves. This presupposes difference-based coding rather than stimulus-based coding. The encoding of such statistically based temporal differences makes it possible to "go beyond" the merely physical features of the stimuli; that is, their single discrete time points and their conduction delays (as related to their neural processing in the brain). This, in turn, makes possible the constitution of "local temporal continuity" of neural activity in one particular region. The concept of "local temporal continuity" signifies the linkage and integration of different discrete time points

  15. Is cortical bone hip? What determines cortical bone properties?

    Science.gov (United States)

    Epstein, Sol

    2007-07-01

    Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal

  16. Statistical mechanics of attractor neural network models with synaptic depression

    International Nuclear Information System (INIS)

    Igarashi, Yasuhiko; Oizumi, Masafumi; Otsubo, Yosuke; Nagata, Kenji; Okada, Masato

    2009-01-01

    Synaptic depression is known to control gain for presynaptic inputs. Since cortical neurons receive thousands of presynaptic inputs, and their outputs are fed into thousands of other neurons, the synaptic depression should influence macroscopic properties of neural networks. We employ simple neural network models to explore the macroscopic effects of synaptic depression. Systems with the synaptic depression cannot be analyzed due to asymmetry of connections with the conventional equilibrium statistical-mechanical approach. Thus, we first propose a microscopic dynamical mean field theory. Next, we derive macroscopic steady state equations and discuss the stabilities of steady states for various types of neural network models.

  17. Genes expressed in specific areas of the human fetal cerebral cortex display distinct patterns of evolution.

    Directory of Open Access Journals (Sweden)

    Nelle Lambert

    2011-03-01

    Full Text Available The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive Broca and Wernicke language areas, as well as surrounding associative areas. We identified hundreds of genes displaying differential expression between the two regions, but no significant difference in gene expression between left and right hemispheres. Validation by qRTPCR and in situ hybridization confirmed the robustness of our approach and revealed novel patterns of area- and layer-specific expression throughout the developing cortex. Genes differentially expressed between cortical areas were significantly associated with fast-evolving non-coding sequences harboring human-specific substitutions that could lead to divergence in their repertoires of transcription factor binding sites. Strikingly, while some of these sequences were accelerated in the human lineage only, many others were accelerated in chimpanzee and/or mouse lineages, indicating that genes important for cortical development may be particularly prone to changes in transcriptional regulation across mammals. Genes differentially expressed between cortical regions were also enriched for transcriptional targets of FoxP2, a key gene for the acquisition of language abilities in humans. Our findings point to a subset of genes with a unique combination of cortical areal expression and evolutionary patterns, suggesting that they play important roles in the transcriptional network underlying human-specific neural traits.

  18. Molecular annotation of integrative feeding neural circuits.

    Science.gov (United States)

    Pérez, Cristian A; Stanley, Sarah A; Wysocki, Robert W; Havranova, Jana; Ahrens-Nicklas, Rebecca; Onyimba, Frances; Friedman, Jeffrey M

    2011-02-02

    The identity of higher-order neurons and circuits playing an associative role to control feeding is unknown. We injected pseudorabies virus, a retrograde tracer, into masseter muscle, salivary gland, and tongue of BAC-transgenic mice expressing GFP in specific neural populations and identified several CNS regions that project multisynaptically to the periphery. MCH and orexin neurons were identified in the lateral hypothalamus, and Nurr1 and Cnr1 in the amygdala and insular/rhinal cortices. Cholera toxin β tracing showed that insular Nurr1(+) and Cnr1(+) neurons project to the amygdala or lateral hypothalamus, respectively. Finally, we show that cortical Cnr1(+) neurons show increased Cnr1 mRNA and c-Fos expression after fasting, consistent with a possible role for Cnr1(+) neurons in feeding. Overall, these studies define a general approach for identifying specific molecular markers for neurons in complex neural circuits. These markers now provide a means for functional studies of specific neuronal populations in feeding or other complex behaviors. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. The human cerebral cortex is neither one nor many: Neuronal distribution reveals two quantitatively different zones in the grey matter, three in the white matter, and explains local variations in cortical folding

    Directory of Open Access Journals (Sweden)

    Pedro F. M. Ribeiro

    2013-09-01

    Full Text Available The human prefrontal cortex has been considered different in several aspects and relatively enlarged compared to the rest of the cortical areas. Here we determine whether the white and gray matter of the prefrontal portion of the human cerebral cortex have similar or different cellular compositions relative to the rest of the cortical regions by applying the Isotropic Fractionator to analyze the distribution of neurons along the entire anteroposterior axis of the cortex, and its relationship with the degree of gyrification, number of neurons under the cortical surface, and other parameters. The prefrontal region shares with the remainder of the cerebral cortex (except for occipital cortex the same relationship between cortical volume and number of neurons. In contrast, both occipital and prefrontal areas vary from other cortical areas in their connectivity through the white matter, with a systematic reduction of cortical connectivity through the white matter and an increase of the mean axon caliber along the anteroposterior axis. These two parameters explain local differences in the distribution of neurons underneath the cortical surface. We also show that local variations in cortical folding are neither a function of local numbers of neurons nor of cortical thickness, but correlate with properties of the white matter, and are best explained by the folding of the white matter surface. Our results suggest that the human cerebral cortex is divided in two zones (occipital and non-occipital that differ in how neurons distributed across their grey matter volume and in three zones (prefrontal, occipital, and non-occipital that differ in how neurons are connected through the white matter. Thus, the human prefrontal cortex has the largest fraction of neuronal connectivity through the white matter and the smallest average axonal caliber in the white matter within the cortex, although its neuronal composition fits the pattern found for other, non

  20. Triadic (ecological, neural, cognitive) niche construction: a scenario of human brain evolution extrapolating tool use and language from the control of reaching actions.

    Science.gov (United States)

    Iriki, Atsushi; Taoka, Miki

    2012-01-12

    Hominin evolution has involved a continuous process of addition of new kinds of cognitive capacity, including those relating to manufacture and use of tools and to the establishment of linguistic faculties. The dramatic expansion of the brain that accompanied additions of new functional areas would have supported such continuous evolution. Extended brain functions would have driven rapid and drastic changes in the hominin ecological niche, which in turn demanded further brain resources to adapt to it. In this way, humans have constructed a novel niche in each of the ecological, cognitive and neural domains, whose interactions accelerated their individual evolution through a process of triadic niche construction. Human higher cognitive activity can therefore be viewed holistically as one component in a terrestrial ecosystem. The brain's functional characteristics seem to play a key role in this triadic interaction. We advance a speculative argument about the origins of its neurobiological mechanisms, as an extension (with wider scope) of the evolutionary principles of adaptive function in the animal nervous system. The brain mechanisms that subserve tool use may bridge the gap between gesture and language--the site of such integration seems to be the parietal and extending opercular cortices.

  1. The Bat as a New Model of Cortical Development.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Ariza, Jeanelle; Rogers, Hailee; Horton-Sparks, Kayla; Kreutz, Anna; Behringer, Richard; Rasweiler, John J; Noctor, Stephen C

    2017-11-09

    The organization of the mammalian cerebral cortex shares fundamental features across species. However, while the radial thickness of grey matter varies within one order of magnitude, the tangential spread of the cortical sheet varies by orders of magnitude across species. A broader sample of model species may provide additional clues for understanding mechanisms that drive cortical expansion. Here, we introduce the bat Carollia perspicillata as a new model species. The brain of C. perspicillata is similar in size to that of mouse but has a cortical neurogenic period at least 5 times longer than mouse, and nearly as long as that of the rhesus macaque, whose brain is 100 times larger. We describe the development of laminar and regional structures, neural precursor cell identity and distribution, immune cell distribution, and a novel population of Tbr2+ cells in the caudal ganglionic eminence of the developing neocortex of C. perspicillata. Our data indicate that unique mechanisms guide bat cortical development, particularly concerning cell cycle length. The bat model provides new perspective on the evolution of developmental programs that regulate neurogenesis in mammalian cerebral cortex, and offers insight into mechanisms that contribute to tangential expansion and gyri formation in the cerebral cortex. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation

    Science.gov (United States)

    Phan, Mimi L.; Bieszczad, Kasia M.

    2016-01-01

    Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded. PMID:26881129

  3. Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation.

    Science.gov (United States)

    Phan, Mimi L; Bieszczad, Kasia M

    2016-01-01

    Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded.

  4. Sensory Cortical Plasticity Participates in the Epigenetic Regulation of Robust Memory Formation

    Directory of Open Access Journals (Sweden)

    Mimi L. Phan

    2016-01-01

    Full Text Available Neuroplasticity remodels sensory cortex across the lifespan. A function of adult sensory cortical plasticity may be capturing available information during perception for memory formation. The degree of experience-dependent remodeling in sensory cortex appears to determine memory strength and specificity for important sensory signals. A key open question is how plasticity is engaged to induce different degrees of sensory cortical remodeling. Neural plasticity for long-term memory requires the expression of genes underlying stable changes in neuronal function, structure, connectivity, and, ultimately, behavior. Lasting changes in transcriptional activity may depend on epigenetic mechanisms; some of the best studied in behavioral neuroscience are DNA methylation and histone acetylation and deacetylation, which, respectively, promote and repress gene expression. One purpose of this review is to propose epigenetic regulation of sensory cortical remodeling as a mechanism enabling the transformation of significant information from experiences into content-rich memories of those experiences. Recent evidence suggests how epigenetic mechanisms regulate highly specific reorganization of sensory cortical representations that establish a widespread network for memory. Thus, epigenetic mechanisms could initiate events to establish exceptionally persistent and robust memories at a systems-wide level by engaging sensory cortical plasticity for gating what and how much information becomes encoded.

  5. Modeling the effects of transcranial magnetic stimulation on cortical circuits.

    Science.gov (United States)

    Esser, Steve K; Hill, Sean L; Tononi, Giulio

    2005-07-01

    Transcranial magnetic stimulation (TMS) is commonly used to activate or inactivate specific cortical areas in a noninvasive manner. Because of technical constraints, the precise effects of TMS on cortical circuits are difficult to assess experimentally. Here, this issue is investigated by constructing a detailed model of a portion of the thalamocortical system and examining the effects of the simulated delivery of a TMS pulse. The model, which incorporates a large number of physiological and anatomical constraints, includes 33,000 spiking neurons arranged in a 3-layered motor cortex and over 5 million intra- and interlayer synaptic connections. The model was validated by reproducing several results from the experimental literature. These include the frequency, timing, dose response, and pharmacological modulation of epidurally recorded responses to TMS (the so-called I-waves), as well as paired-pulse response curves consistent with data from several experimental studies. The modeled responses to simulated TMS pulses in different experimental paradigms provide a detailed, self-consistent account of the neural and synaptic activities evoked by TMS within prototypical cortical circuits.

  6. 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.

  7. Learning to Produce Syllabic Speech Sounds via Reward-Modulated Neural Plasticity

    Science.gov (United States)

    Warlaumont, Anne S.; Finnegan, Megan K.

    2016-01-01

    At around 7 months of age, human infants begin to reliably produce well-formed syllables containing both consonants and vowels, a behavior called canonical babbling. Over subsequent months, the frequency of canonical babbling continues to increase. How the infant’s nervous system supports the acquisition of this ability is unknown. Here we present a computational model that combines a spiking neural network, reinforcement-modulated spike-timing-dependent plasticity, and a human-like vocal tract to simulate the acquisition of canonical babbling. Like human infants, the model’s frequency of canonical babbling gradually increases. The model is rewarded when it produces a sound that is more auditorily salient than sounds it has previously produced. This is consistent with data from human infants indicating that contingent adult responses shape infant behavior and with data from deaf and tracheostomized infants indicating that hearing, including hearing one’s own vocalizations, is critical for canonical babbling development. Reward receipt increases the level of dopamine in the neural network. The neural network contains a reservoir with recurrent connections and two motor neuron groups, one agonist and one antagonist, which control the masseter and orbicularis oris muscles, promoting or inhibiting mouth closure. The model learns to increase the number of salient, syllabic sounds it produces by adjusting the base level of muscle activation and increasing their range of activity. Our results support the possibility that through dopamine-modulated spike-timing-dependent plasticity, the motor cortex learns to harness its natural oscillations in activity in order to produce syllabic sounds. It thus suggests that learning to produce rhythmic mouth movements for speech production may be supported by general cortical learning mechanisms. The model makes several testable predictions and has implications for our understanding not only of how syllabic vocalizations develop

  8. Signal transfer within a cultured asymmetric cortical neuron circuit.

    Science.gov (United States)

    Isomura, Takuya; Shimba, Kenta; Takayama, Yuzo; Takeuchi, Akimasa; Kotani, Kiyoshi; Jimbo, Yasuhiko

    2015-12-01

    Simplified neuronal circuits are required for investigating information representation in nervous systems and for validating theoretical neural network models. Here, we developed patterned neuronal circuits using micro fabricated devices, comprising a micro-well array bonded to a microelectrode-array substrate. The micro-well array consisted of micrometre-scale wells connected by tunnels, all contained within a silicone slab called a micro-chamber. The design of the micro-chamber confined somata to the wells and allowed axons to grow through the tunnels bidirectionally but with a designed, unidirectional bias. We guided axons into the point of the arrow structure where one of the two tunnel entrances is located, making that the preferred direction. When rat cortical neurons were cultured in the wells, their axons grew through the tunnels and connected to neurons in adjoining wells. Unidirectional burst transfers and other asymmetric signal-propagation phenomena were observed via the substrate-embedded electrodes. Seventy-nine percent of burst transfers were in the forward direction. We also observed rapid propagation of activity from sites of local electrical stimulation, and significant effects of inhibitory synapse blockade on bursting activity. These results suggest that this simple, substrate-controlled neuronal circuit can be applied to develop in vitro models of the function of cortical microcircuits or deep neural networks, better to elucidate the laws governing the dynamics of neuronal networks.

  9. Signal transfer within a cultured asymmetric cortical neuron circuit

    Science.gov (United States)

    Isomura, Takuya; Shimba, Kenta; Takayama, Yuzo; Takeuchi, Akimasa; Kotani, Kiyoshi; Jimbo, Yasuhiko

    2015-12-01

    Objective. Simplified neuronal circuits are required for investigating information representation in nervous systems and for validating theoretical neural network models. Here, we developed patterned neuronal circuits using micro fabricated devices, comprising a micro-well array bonded to a microelectrode-array substrate. Approach. The micro-well array consisted of micrometre-scale wells connected by tunnels, all contained within a silicone slab called a micro-chamber. The design of the micro-chamber confined somata to the wells and allowed axons to grow through the tunnels bidirectionally but with a designed, unidirectional bias. We guided axons into the point of the arrow structure where one of the two tunnel entrances is located, making that the preferred direction. Main results. When rat cortical neurons were cultured in the wells, their axons grew through the tunnels and connected to neurons in adjoining wells. Unidirectional burst transfers and other asymmetric signal-propagation phenomena were observed via the substrate-embedded electrodes. Seventy-nine percent of burst transfers were in the forward direction. We also observed rapid propagation of activity from sites of local electrical stimulation, and significant effects of inhibitory synapse blockade on bursting activity. Significance. These results suggest that this simple, substrate-controlled neuronal circuit can be applied to develop in vitro models of the function of cortical microcircuits or deep neural networks, better to elucidate the laws governing the dynamics of neuronal networks.

  10. Computational modeling of epidural cortical stimulation

    Science.gov (United States)

    Wongsarnpigoon, Amorn; Grill, Warren M.

    2008-12-01

    Epidural cortical stimulation (ECS) is a developing therapy to treat neurological disorders. However, it is not clear how the cortical anatomy or the polarity and position of the electrode affects current flow and neural activation in the cortex. We developed a 3D computational model simulating ECS over the precentral gyrus. With the electrode placed directly above the gyrus, about half of the stimulus current flowed through the crown of the gyrus while current density was low along the banks deep in the sulci. Beneath the electrode, neurons oriented perpendicular to the cortical surface were depolarized by anodic stimulation, and neurons oriented parallel to the boundary were depolarized by cathodic stimulation. Activation was localized to the crown of the gyrus, and neurons on the banks deep in the sulci were not polarized. During regulated voltage stimulation, the magnitude of the activating function was inversely proportional to the thickness of the CSF and dura. During regulated current stimulation, the activating function was not sensitive to the thickness of the dura but was slightly more sensitive than during regulated voltage stimulation to the thickness of the CSF. Varying the width of the gyrus and the position of the electrode altered the distribution of the activating function due to changes in the orientation of the neurons beneath the electrode. Bipolar stimulation, although often used in clinical practice, reduced spatial selectivity as well as selectivity for neuron orientation.

  11. A developmental perspective on the neural bases of human empathy.

    Science.gov (United States)

    Tousignant, Béatrice; Eugène, Fanny; Jackson, Philip L

    2017-08-01

    While empathy has been widely studied in philosophical and psychological literatures, recent advances in social neuroscience have shed light on the neural correlates of this complex interpersonal phenomenon. In this review, we provide an overview of brain imaging studies that have investigated the neural substrates of human empathy. Based on existing models of the functional architecture of empathy, we review evidence of the neural underpinnings of each main component, as well as their development from infancy. Although early precursors of affective sharing and self-other distinction appear to be present from birth, recent findings also suggest that even higher-order components of empathy such as perspective-taking and emotion regulation demonstrate signs of development during infancy. This merging of developmental and social neuroscience literature thus supports the view that ontogenic development of empathy is rooted in early infancy, well before the emergence of verbal abilities. With age, the refinement of top-down mechanisms may foster more appropriate empathic responses, thus promoting greater altruistic motivation and prosocial behaviors. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

    Science.gov (United States)

    Chen, Song; Zhang, Wei; Wang, Ji-Ming; Duan, Hong-Tao; Kong, Jia-Hui; Wang, Yue-Xin; Dong, Meng; Bi, Xue; Song, Jian

    2016-01-01

    AIM To investigate whether umbilical cord human mesenchymal stem cell (UC-MSC) was able to differentiate into neural stem cell and neuron in vitro. METHODS The umbilical cords were obtained from pregnant women with their written consent and the approval of the Clinic Ethnics Committee. UC-MSC were isolated by adherent culture in the medium contains 20% fetal bovine serum (FBS), then they were maintained in the medium contain 10% FBS and induced to neural cells in neural differentiation medium. We investigated whether UC-MSC was able to differentiate into neural stem cell and neuron in vitro by using flow cytometry, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence (IF) analyzes. RESULTS A substantial number of UC-MSC was harvested using the tissue explants adherent method at about 2wk. Flow cytometric study revealed that these cells expressed common markers of MSCs, such as CD105 (SH2), CD73 (SH3) and CD90. After induction of differentiation of neural stem cells, the cells began to form clusters; RT-PCR and IF showed that the neuron specific enolase (NSE) and neurogenic differentiation 1-positive cells reached 87.3%±14.7% and 72.6%±11.8%, respectively. Cells showed neuronal cell differentiation after induced, including neuron-like protrusions, plump cell body, obviously and stronger refraction. RT-PCR and IF analysis showed that microtubule-associated protein 2 (MAP2) and nuclear factor-M-positive cells reached 43.1%±10.3% and 69.4%±19.5%, respectively. CONCLUSION Human umbilical cord derived MSCs can be cultured and proliferated in vitro and differentiate into neural stem cells, which may be a valuable source for cell therapy of neurodegenerative eye diseases. PMID:26949608

  13. Differentiation of isolated human umbilical cord mesenchymal stem cells into neural stem cells

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    Song Chen

    2016-01-01

    Full Text Available AIM: To investigate whether umbilical cord human mesenchymal stem cell (UC-MSC was able to differentiate into neural stem cell and neuron in vitro. METHODS: The umbilical cords were obtained from pregnant women with their written consent and the approval of the Clinic Ethnics Committee. UC-MSC were isolated by adherent culture in the medium contains 20% fetal bovine serum (FBS, then they were maintained in the medium contain 10% FBS and induced to neural cells in neural differentiation medium. We investigated whether UC-MSC was able to differentiate into neural stem cell and neuron in vitro by using flow cytometry, reverse transcriptase-polymerase chain reaction (RT-PCR and immunofluorescence (IF analyzes. RESULTS: A substantial number of UC-MSC was harvested using the tissue explants adherent method at about 2wk. Flow cytometric study revealed that these cells expressed common markers of MSCs, such as CD105 (SH2, CD73 (SH3 and CD90. After induction of differentiation of neural stem cells, the cells began to form clusters; RT-PCR and IF showed that the neuron specific enolase (NSE and neurogenic differentiation 1-positive cells reached 87.3%±14.7% and 72.6%±11.8%, respectively. Cells showed neuronal cell differentiation after induced, including neuron-like protrusions, plump cell body, obviously and stronger refraction. RT-PCR and IF analysis showed that microtubule-associated protein 2 (MAP2 and nuclear factor-M-positive cells reached 43.1%±10.3% and 69.4%±19.5%, respectively. CONCLUSION: Human umbilical cord derived MSCs can be cultured and proliferated in vitro and differentiate into neural stem cells, which may be a valuable source for cell therapy of neurodegenerative eye diseases.

  14. Neural prediction errors reveal a risk-sensitive reinforcement-learning process in the human brain.

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    Niv, Yael; Edlund, Jeffrey A; Dayan, Peter; O'Doherty, John P

    2012-01-11

    Humans and animals are exquisitely, though idiosyncratically, sensitive to risk or variance in the outcomes of their actions. Economic, psychological, and neural aspects of this are well studied when information about risk is provided explicitly. However, we must normally learn about outcomes from experience, through trial and error. Traditional models of such reinforcement learning focus on learning about the mean reward value of cues and ignore higher order moments such as variance. We used fMRI to test whether the neural correlates of human reinforcement learning are sensitive to experienced risk. Our analysis focused on anatomically delineated regions of a priori interest in the nucleus accumbens, where blood oxygenation level-dependent (BOLD) signals have been suggested as correlating with quantities derived from reinforcement learning. We first provide unbiased evidence that the raw BOLD signal in these regions corresponds closely to a reward prediction error. We then derive from this signal the learned values of cues that predict rewards of equal mean but different variance and show that these values are indeed modulated by experienced risk. Moreover, a close neurometric-psychometric coupling exists between the fluctuations of the experience-based evaluations of risky options that we measured neurally and the fluctuations in behavioral risk aversion. This suggests that risk sensitivity is integral to human learning, illuminating economic models of choice, neuroscientific models of affective learning, and the workings of the underlying neural mechanisms.

  15. Histological features of layers and sublayers in cortical visual areas V1 and V2 of chimpanzees, macaque monkeys, and humans

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    Balaram P

    2014-09-01

    Full Text Available Pooja Balaram, Nicole A Young, Jon H Kaas Department of Psychology, Vanderbilt University, Nashville, TN, USA Abstract: The layers and sublayers of primary visual cortex, or V1, in primates are easily distinguishable compared to those in other cortical areas, and are especially distinct in anthropoid primates – monkeys, apes, and humans – where they also vary in histological appearance. This variation in primate-specific specialization has led to a longstanding confusion over the identity of layer 4 and its proposed sublayers in V1. As the application of different histological markers relate to the issue of defining and identifying layers and sublayers, we applied four traditional and four more recent histological markers to brain sections of V1 and adjoining secondary visual cortex (V2 in macaque monkeys, chimpanzees, and humans in order to compare identifiable layers and sublayers in both cortical areas across these species. The use of Nissl, neuronal nuclear antigen (NeuN, Gallyas myelin, cytochrome oxidase (CO, acetylcholinesterase (AChE, nonphosphorylated neurofilament H (SMI-32, parvalbumin (PV, and vesicular glutamate transporter 2 (VGLUT2 preparations support the conclusion that the most popular scheme of V1 lamination, that of Brodmann, misidentifies sublayers of layer 3 (3Bβ and 3C as sublayers of layer 4 (4A and 4B, and that the specialized sublayer of layer 3 in monkeys, 3Bβ, is not present in humans. These differences in interpretation are important as they relate to the proposed functions of layer 4 in primate species, where layer 4 of V1 is a layer that receives and processes information from the visual thalamus, and layer 3 is a layer that transforms and distributes information to other cortical areas. Keywords: area 17, area 18, cortical layers, histology, immunohistochemistry

  16. Transcranial magnetic stimulation provides means to assess cortical plasticity and excitability in humans with fragile X syndrome and autism spectrum disorder

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    Lindsay M Oberman

    2010-06-01

    Full Text Available Fragile X Syndrome (FXS is the most common heritable cause of intellectual disability. In vitro electrophysiologic data from mouse models of FXS suggest that loss of Fragile X Mental Retardation Protein (FMRP affects intracortical excitability and synaptic plasticity. Specifically, the cortex appears hyperexcitable, and use-dependent long-term potentiation (LTP and long-term depression (LTD of synaptic strength are abnormal. Though animal models provide important information, FXS and other neurodevelopmental disorders are human diseases and as such translational research to evaluate cortical excitability and plasticity must be applied in the human. Transcranial magnetic stimulation (TMS paradigms have recently been developed to noninvasively investigate cortical excitability using paired-pulse stimulation, as well as LTP- and LTD-like synaptic plasticity in response to theta burst stimulation (TBS in vivo in the human. TBS applied on consecutive days can be used to measure metaplasticity (the ability of the synapse to undergo a second plastic change following a recent induction of plasticity. The current study investigated intracortical inhibition, plasticity and metaplasticity in full mutation females with FXS, participants with autism spectrum disorders (ASD, and neurotypical controls. Results suggest that intracortical inhibition is normal in participants with FXS, while plasticity and metaplasticity appear abnormal. ASD participants showed abnormalities in plasticity and metaplasticity, as well as heterogeneity in intracortical inhibition. Our findings highlight the utility of noninvasive neurophysiological measures to translate insights from animal models to humans with neurodevelopmental disorders, and thus provide direct confirmation of cortical dysfunction in patients with FXS and ASD.

  17. A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and roadmap for future research

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    Phillips, Mary L; Swartz, Holly A.

    2014-01-01

    Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual

  18. The neural code for face orientation in the human fusiform face area.

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    Ramírez, Fernando M; Cichy, Radoslaw M; Allefeld, Carsten; Haynes, John-Dylan

    2014-09-03

    Humans recognize faces and objects with high speed and accuracy regardless of their orientation. Recent studies have proposed that orientation invariance in face recognition involves an intermediate representation where neural responses are similar for mirror-symmetric views. Here, we used fMRI, multivariate pattern analysis, and computational modeling to investigate the neural encoding of faces and vehicles at different rotational angles. Corroborating previous studies, we demonstrate a representation of face orientation in the fusiform face-selective area (FFA). We go beyond these studies by showing that this representation is category-selective and tolerant to retinal translation. Critically, by controlling for low-level confounds, we found the representation of orientation in FFA to be compatible with a linear angle code. Aspects of mirror-symmetric coding cannot be ruled out when FFA mean activity levels are considered as a dimension of coding. Finally, we used a parametric family of computational models, involving a biased sampling of view-tuned neuronal clusters, to compare different face angle encoding models. The best fitting model exhibited a predominance of neuronal clusters tuned to frontal views of faces. In sum, our findings suggest a category-selective and monotonic code of face orientation in the human FFA, in line with primate electrophysiology studies that observed mirror-symmetric tuning of neural responses at higher stages of the visual system, beyond the putative homolog of human FFA. Copyright © 2014 the authors 0270-6474/14/3412155-13$15.00/0.

  19. The relationship between neuropsychological tests of visuospatial function and lobar cortical thickness.

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    Zink, Davor N; Miller, Justin B; Caldwell, Jessica Z K; Bird, Christopher; Banks, Sarah J

    2018-06-01

    Tests of visuospatial function are often administered in comprehensive neuropsychological evaluations. These tests are generally considered assays of parietal lobe function; however, the neural correlates of these tests, using modern imaging techniques, are not well understood. In the current study we investigated the relationship between three commonly used tests of visuospatial function and lobar cortical thickness in each hemisphere. Data from 374 patients who underwent a neuropsychological evaluation and MRI scans in an outpatient dementia clinic were included in the analysis. We examined the relationships between cortical thickness, as assessed with Freesurfer, and performance on three tests: Judgment of Line Orientation (JoLO), Block Design (BD) from the Fourth edition of the Wechsler Adult Intelligence Scale, and Brief Visuospatial Memory Test-Revised Copy Trial (BVMT-R-C) in patients who showed overall average performance on these tasks. Using a series of multiple regression models, we assessed which lobe's overall cortical thickness best predicted test performance. Among the individual lobes, JoLO performance was best predicted by cortical thickness in the right temporal lobe. BD performance was best predicted by cortical thickness in the right parietal lobe, and BVMT-R-C performance was best predicted by cortical thickness in the left parietal lobe. Performance on constructional tests of visuospatial function appears to correspond best with underlying cortical thickness of the parietal lobes, while performance on visuospatial judgment tests appears to correspond best to temporal lobe thickness. Future research using voxel-wise and connectivity techniques and including more diverse samples will help further understanding of the regions and networks involved in visuospatial tests.

  20. The effect of binaural beats on verbal working memory and cortical connectivity.

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    Beauchene, Christine; Abaid, Nicole; Moran, Rosalyn; Diana, Rachel A; Leonessa, Alexander

    2017-04-01

    Synchronization in activated regions of cortical networks affect the brain's frequency response, which has been associated with a wide range of states and abilities, including memory. A non-invasive method for manipulating cortical synchronization is binaural beats. Binaural beats take advantage of the brain's response to two pure tones, delivered independently to each ear, when those tones have a small frequency mismatch. The mismatch between the tones is interpreted as a beat frequency, which may act to synchronize cortical oscillations. Neural synchrony is particularly important for working memory processes, the system controlling online organization and retention of information for successful goal-directed behavior. Therefore, manipulation of synchrony via binaural beats provides a unique window into working memory and associated connectivity of cortical networks. In this study, we examined the effects of different acoustic stimulation conditions during an N-back working memory task, and we measured participant response accuracy and cortical network topology via EEG recordings. Six acoustic stimulation conditions were used: None, Pure Tone, Classical Music, 5 Hz binaural beats, 10 Hz binaural beats, and 15 Hz binaural beats. We determined that listening to 15 Hz binaural beats during an N-Back working memory task increased the individual participant's accuracy, modulated the cortical frequency response, and changed the cortical network connection strengths during the task. Only the 15 Hz binaural beats produced significant change in relative accuracy compared to the None condition. Listening to 15 Hz binaural beats during the N-back task activated salient frequency bands and produced networks characterized by higher information transfer as compared to other auditory stimulation conditions.

  1. Neurofeedback of slow cortical potentials: neural mechanisms and feasibility of a placebo-controlled design in healthy adults

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    Holger eGevensleben

    2014-12-01

    Full Text Available To elucidate basic mechanisms underlying neurofeedback we investigated neural mechanisms of training of slow cortical potentials by considering EEG- and fMRI. Additionally, we analyzed the feasibility of a double-blind, placebo-controlled design in NF research based on regulation performance during treatment sessions and self-assessment of the participants. Twenty healthy adults participated in 16 sessions of SCP training: 9 participants received regular SCP training, 11 participants received sham feedback. At three time points (pre, intermediate, post fMRI and EEG/ERP-measurements were conducted during a continuous performance test (CPT. Performance-data during the sessions (regulation performance in the treatment group and the placebo group were analyzed. Analysis of EEG-activity revealed in the SCP group a strong enhancement of the CNV (electrode Cz at the intermediate assessment, followed by a decrease back to baseline at the post-treatment assessment. In contrast, in the placebo group a continuous but smaller increase of the CNV could be obtained from pre to post assessment. The increase of the CNV in the SCP group at intermediate testing was superior to the enhancement in the placebo group. The changes of the CNV were accompanied by a continuous improvement in the test performance of the CPT from pre to intermediate to post assessment comparable in both groups. The change of the CNV in the SCP group is interpreted as an indicator of neural plasticity and efficiency while an increase of the CNV in the placebo group might reflect learning and improved timing due to the frequent task repetition.In the fMRI analysis evidence was obtained for neuronal plasticity. After regular SCP neurofeedback activation in the posterior parietal cortex decreased from the pre- to the intermediate measurement and increased again in the post measurement, inversely following the U-shaped increase and decrease of the tCNV EEG amplitude in the SCP-trained group

  2. A scale out approach towards neural induction of human induced pluripotent stem cells for neurodevelopmental toxicity studies.

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    Miranda, Cláudia C; Fernandes, Tiago G; Pinto, Sandra N; Prieto, Manuel; Diogo, M Margarida; Cabral, Joaquim M S

    2018-05-21

    Stem cell's unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs are capable of undergoing neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells. Furthermore, this platform can be applied towards the study of the effect of neurotoxic molecules that impair normal embryonic development. As a proof of concept, the neural teratogenic potential of the antiepileptic drug valproic acid (VPA) was analyzed. It was verified that exposure to VPA, close to typical dosage values (0.3 to 0.75 mM), led to a prevalence of NP structures over neuronal differentiation, as confirmed by analysis of the expression of neural cell adhesion molecule, as well as neural rosette number and morphology assessment. The methodology proposed herein for the generation and neural differentiation of hiPSC aggregates can potentially complement current toxicity tests such as the humanized embryonic stem cell test for the detection of teratogenic compounds that can interfere with normal embryonic development. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. ERK-dependent and -independent pathways trigger human neural progenitor cell migration

    International Nuclear Information System (INIS)

    Moors, Michaela; Cline, Jason E.; Abel, Josef; Fritsche, Ellen

    2007-01-01

    Besides differentiation and apoptosis, cell migration is a basic process in brain development in which neural cells migrate several centimeters within the developing brain before reaching their proper positions and forming the right connections. For identifying signaling events that control neural migration and are therefore potential targets of chemicals to disturb normal brain development, we developed a human neurosphere-based migration assay based on normal human neural progenitor (NHNP) cells, in which the distance is measured that cells wander over time. Applying this assay, we investigated the role of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP cell migration. Exposure to model substances like ethanol or phorbol 12-myristate 13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2 phosphorylation and inhibited cell migration. We identified protein kinase C (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases governing ERK1/2 activation, thereby controlling NHNP cell migration. Additionally, treatments with src kinase inhibitors led to a diminished cell migration without affecting ERK1/2 phosphorylation. Based on these results, we postulate that migration of NHNP cells is controlled via ERK1/2-dependent and -independent pathways

  4. Music-induced cortical plasticity and lateral inhibition in the human auditory cortex as foundations for tonal tinnitus treatment

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    Christo ePantev

    2012-06-01

    Full Text Available Over the past 15 years, we have studied plasticity in the human auditory cortex by means of magnetoencephalography (MEG. Two main topics nurtured our curiosity: the effects of musical training on plasticity in the auditory system, and the effects of lateral inhibition. One of our plasticity studies found that listening to notched music for three hours inhibited the neuronal activity in the auditory cortex that corresponded to the center-frequency of the notch, suggesting suppression of neural activity by lateral inhibition. Crucially, the overall effects of lateral inhibition on human auditory cortical activity were stronger than the habituation effects. Based on these results we developed a novel treatment strategy for tonal tinnitus - tailor-made notched music training (TMNMT. By notching the music energy spectrum around the individual tinnitus frequency, we intended to attract lateral inhibition to auditory neurons involved in tinnitus perception. So far, the training strategy has been evaluated in two studies. The results of the initial long-term controlled study (12 months supported the validity of the treatment concept: subjective tinnitus loudness and annoyance were significantly reduced after TMNMT but not when notching spared the tinnitus frequencies. Correspondingly, tinnitus-related auditory evoked fields (AEFs were significantly reduced after training. The subsequent short-term (5 days training study indicated that training was more effective in the case of tinnitus frequencies ≤ 8 kHz compared to tinnitus frequencies > 8 kHz, and that training should be employed over a long-term in order to induce more persistent effects. Further development and evaluation of TMNMT therapy are planned. A goal is to transfer this novel, completely non-invasive, and low-cost treatment approach for tonal tinnitus into routine clinical practice.

  5. Neural correlates of attitude change following positive and negative advertisements

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    Junko Kato

    2009-05-01

    Full Text Available Understanding changes in attitudes towards others is critical to understanding human behaviour. Neuropolitical studies have found that the activation of emotion-related areas in the brain is linked to resilient political preferences, and neuroeconomic research has analysed the neural correlates of social preferences that favour or oppose consideration of intrinsic rewards. This study aims to identify the neural correlates in the prefrontal cortices of changes in political attitudes toward others that are linked to social cognition. Functional magnetic resonance imaging (fMRI experiments have presented videos from previous electoral campaigns and television commercials for major cola brands and then used the subjects’ self-rated affinity toward political candidates as behavioural indicators. After viewing negative campaign videos, subjects showing stronger fMRI activation in the dorsolateral prefrontal cortex lowered their ratings of the candidate they originally supported more than did those with smaller fMRI signal changes in the same region. Subjects showing stronger activation in the medial prefrontal cortex tended to increase their ratings more than did those with less activation. The same regions were not activated by viewing negative advertisements for cola. Correlations between the self-rated values and the neural signal changes underscore the metric representation of observed decisions (i.e., whether to support or not in the brain. This indicates that neurometric analysis may contribute to the exploration of the neural correlates of daily social behaviour.

  6. Dissociation of Subtraction and Multiplication in the Right Parietal Cortex: Evidence from Intraoperative Cortical Electrostimulation

    Science.gov (United States)

    Yu, Xiaodan; Chen, Chuansheng; Pu, Song; Wu, Chenxing; Li, Yongnian; Jiang, Tao; Zhou, Xinlin

    2011-01-01

    Previous research has consistently shown that the left parietal cortex is critical for numerical processing, but the role of the right parietal lobe has been much less clear. This study used the intraoperative cortical electrical stimulation approach to investigate neural dissociation in the right parietal cortex for subtraction and…

  7. Noninvasive scalp recording of cortical auditory evoked potentials in the alert macaque monkey.

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    Itoh, Kosuke; Nejime, Masafumi; Konoike, Naho; Nakada, Tsutomu; Nakamura, Katsuki

    2015-09-01

    Scalp-recorded evoked potentials (EP) provide researchers and clinicians with irreplaceable means for recording stimulus-related neural activities in the human brain, due to its high temporal resolution, handiness, and, perhaps more importantly, non-invasiveness. This work recorded the scalp cortical auditory EP (CAEP) in unanesthetized monkeys by using methods that are essentially identical to those applied to humans. Young adult rhesus monkeys (Macaca mulatta, 5-7 years old) were seated in a monkey chair, and their head movements were partially restricted by polystyrene blocks and tension poles placed around their head. Individual electrodes were fixated on their scalp using collodion according to the 10-20 system. Pure tone stimuli were presented while electroencephalograms were recorded from up to nineteen channels, including an electrooculogram channel. In all monkeys (n = 3), the recorded CAEP comprised a series of positive and negative deflections, labeled here as macaque P1 (mP1), macaque N1 (mN1), macaque P2 (mP2), and macaque N2 (mN2), and these transient responses to sound onset were followed by a sustained potential that continued for the duration of the sound, labeled the macaque sustained potential (mSP). mP1, mN2 and mSP were the prominent responses, and they had maximal amplitudes over frontal/central midline electrode sites, consistent with generators in auditory cortices. The study represents the first noninvasive scalp recording of CAEP in alert rhesus monkeys, to our knowledge. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Conversion of adult human peripheral blood mononuclear cells into induced neural stem cell by using episomal vectors

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    Xihe Tang

    2016-03-01

    Full Text Available Human neural stem cells (NSCs hold great promise for research and therapy in neural diseases. Many studies have shown direct induction of NSCs from human fibroblasts, which require an invasive skin biopsy and a prolonged period of expansion in cell culture prior to use. Peripheral blood (PB is routinely used in medical diagnoses, and represents a noninvasive and easily accessible source of cells. Here we show direct derivation of NSCs from adult human PB mononuclear cells (PB-MNCs by employing episomal vectors for transgene delivery. These induced NSCs (iNSCs can expand more than 60 passages, can exhibit NSC morphology, gene expression, differentiation potential, and self-renewing capability and can give rise to multiple functional neural subtypes and glial cells in vitro. Furthermore, the iNSCs carry a specific regional identity and have electrophysiological activity upon differentiation. Our findings provide an easily accessible approach for generating human iNSCs which will facilitate disease modeling, drug screening, and possibly regenerative medicine.

  9. Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

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    Eneh, C. T. M., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Töyräs, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Jurvelin, J. S., E-mail: jukka.jurvelin@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211, Finland and Diagnostic Imaging Center, Kuopio University Hospital, P.O. Box 100, Kuopio FI-70029 (Finland); Malo, M. K. H., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi; Liukkonen, J., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Department of Applied Physics, University of Eastern Finland, P.O. Box 1627, Kuopio FI-70211 (Finland); Karjalainen, J. P., E-mail: chibuzor.eneh@uef.fi, E-mail: markus.malo@uef.fi, E-mail: janne.karjalainen@boneindex.fi, E-mail: jukka.liukkonen@gmail.com, E-mail: juha.toyras@uef.fi [Bone Index Finland Ltd., P.O. Box 1188, Kuopio FI-70211 (Finland)

    2016-05-15

    Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R{sup 2} ≥ 0.493, p < 0.01 and R{sup 2} ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated

  10. Effect of porosity, tissue density, and mechanical properties on radial sound speed in human cortical bone

    International Nuclear Information System (INIS)

    Eneh, C. T. M.; Töyräs, J.; Jurvelin, J. S.; Malo, M. K. H.; Liukkonen, J.; Karjalainen, J. P.

    2016-01-01

    Purpose: The purpose of this study was to investigate the effect of simultaneous changes in cortical porosity, tissue mineral density, and elastic properties on radial speed of sound (SOS) in cortical bone. The authors applied quantitative pulse-echo (PE) ultrasound techniques that hold much potential especially for screening of osteoporosis at primary healthcare facilities. Currently, most PE measurements of cortical thickness, a well-known indicator of fracture risk, use a predefined estimate for SOS in bone to calculate thickness. Due to variation of cortical bone porosity, the use of a constant SOS value propagates to an unknown error in cortical thickness assessment by PE ultrasound. Methods: The authors conducted 2.25 and 5.00 MHz focused PE ultrasound time of flight measurements on femoral diaphyses of 18 cadavers in vitro. Cortical porosities of the samples were determined using microcomputed tomography and related to SOS in the samples. Additionally, the effect of cortical bone porosity and mechanical properties of the calcified matrix on SOS was investigated using numerical finite difference time domain simulations. Results: Both experimental measurements and simulations demonstrated significant negative correlation between radial SOS and cortical porosity (R"2 ≥ 0.493, p < 0.01 and R"2 ≥ 0.989, p < 0.01, respectively). When a constant SOS was assumed for cortical bone, the error due to variation of cortical bone porosity (4.9%–16.4%) was about 6% in the cortical thickness assessment in vitro. Conclusions: Use of a predefined, constant value for radial SOS in cortical bone, i.e., neglecting the effect of measured variation in cortical porosity, propagated to an error of 6% in cortical thickness. This error can be critical as characteristic cortical thinning of 1.10% ± 1.06% per yr decreases bending strength of the distal radius and results in increased fragility in postmenopausal women. Provided that the cortical porosity can be estimated in vivo

  11. Neural Encoding and Decoding with Deep Learning for Dynamic Natural Vision.

    Science.gov (United States)

    Wen, Haiguang; Shi, Junxing; Zhang, Yizhen; Lu, Kun-Han; Cao, Jiayue; Liu, Zhongming

    2017-10-20

    Convolutional neural network (CNN) driven by image recognition has been shown to be able to explain cortical responses to static pictures at ventral-stream areas. Here, we further showed that such CNN could reliably predict and decode functional magnetic resonance imaging data from humans watching natural movies, despite its lack of any mechanism to account for temporal dynamics or feedback processing. Using separate data, encoding and decoding models were developed and evaluated for describing the bi-directional relationships between the CNN and the brain. Through the encoding models, the CNN-predicted areas covered not only the ventral stream, but also the dorsal stream, albeit to a lesser degree; single-voxel response was visualized as the specific pixel pattern that drove the response, revealing the distinct representation of individual cortical location; cortical activation was synthesized from natural images with high-throughput to map category representation, contrast, and selectivity. Through the decoding models, fMRI signals were directly decoded to estimate the feature representations in both visual and semantic spaces, for direct visual reconstruction and semantic categorization, respectively. These results corroborate, generalize, and extend previous findings, and highlight the value of using deep learning, as an all-in-one model of the visual cortex, to understand and decode natural vision. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Multi-dimensional modulations of alpha and gamma cortical dynamics following mindfulness-based cognitive therapy in Major Depressive Disorder

    NARCIS (Netherlands)

    Schoenberg, P.L.; Speckens, A.E.M.

    2015-01-01

    To illuminate candidate neural working mechanisms of Mindfulness-Based Cognitive Therapy (MBCT) in the treatment of recurrent depressive disorder, parallel to the potential interplays between modulations in electro-cortical dynamics and depressive symptom severity and self-compassionate experience.

  13. A Preliminary Study of the Influence of Age of Onset and Childhood Trauma on Cortical Thickness in Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Natalia Jaworska

    2014-01-01

    Full Text Available Background. Major depressive disorder (MDD neural underpinnings may differ based on onset age and childhood trauma. We assessed cortical thickness in patients who differed in age of MDD onset and examined trauma history influence. Methods. Adults with MDD (N=36 and controls (HC; N=18 underwent magnetic resonance imaging. Twenty patients had MDD onset 25 years of age (adult onset. The MDD group was also subdivided into those with (N=12 and without (N=19 physical and/or sexual abuse as assessed by the Childhood Trauma Questionnaire (CTQ. Cortical thickness was analyzed with FreeSurfer software. Results. Thicker frontal pole and a tendency for thinner transverse temporal cortices existed in MDD. The former was driven by the pediatric onset group and abuse history (independently, particularly in the right frontal pole. Inverse correlations existed between CTQ scores and frontal pole cortex thickness. A similar inverse relation existed with left inferior and right superior parietal cortex thickness. The superior temporal cortex tended to be thinner in pediatric versus adult onset groups with childhood abuse. Conclusions. This preliminary work suggests neural differences between pediatric and adult MDD onset. Trauma history also contributes to cytoarchitectural modulation. Thickened frontal pole cortices as a compensatory mechanism in MDD warrant evaluation.

  14. Different cortical mechanisms for spatial vs. feature-based attentional selection in visual working memory

    Directory of Open Access Journals (Sweden)

    Anna Heuer

    2016-08-01

    Full Text Available The limited capacity of visual working memory necessitates attentional mechanisms that selectively update and maintain only the most task-relevant content. Psychophysical experiments have shown that the retroactive selection of memory content can be based on visual properties such as location or shape, but the neural basis for such differential selection is unknown. For example, it is not known if there are different cortical modules specialized for spatial versus feature-based mnemonic attention, in the same way that has been demonstrated for attention to perceptual input. Here, we used transcranial magnetic stimulation (TMS to identify areas in human parietal and occipital cortex involved in the selection of objects from memory based on cues to their location (spatial information or their shape (featural information. We found that TMS over the supramarginal gyrus (SMG selectively facilitated spatial selection, whereas TMS over the lateral occipital cortex selectively enhanced feature-based selection for remembered objects in the contralateral visual field. Thus, different cortical regions are responsible for spatial vs. feature-based selection of working memory representations. Since the same regions are involved in attention to external events, these new findings indicate overlapping mechanisms for attentional control over perceptual input and mnemonic representations.

  15. Immortalization of human neural stem cells with the c-myc mutant T58A.

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    Lidia De Filippis

    Full Text Available Human neural stem cells (hNSC represent an essential source of renewable brain cells for both experimental studies and cell replacement therapies. Their relatively slow rate of proliferation and physiological senescence in culture make their use cumbersome under some experimental and pre-clinical settings. The immortalization of hNSC with the v-myc gene (v-IhNSC has been shown to generate stem cells endowed with enhanced proliferative capacity, which greatly facilitates the study of hNSCs, both in vitro and in vivo. Despite the excellent safety properties displayed by v-IhNSCs--which do not transform in vitro and are not tumorigenic in vivo--the v-myc gene contains several mutations and recombination elements, whose role(s and effects remains to be elucidated, yielding unresolved safety concerns. To address this issue, we used a c-myc T58A retroviral vector to establish an immortal cell line (T-IhNSC from the same hNSCs used to generate the original v-IhNSCs and compared their characteristics with the latter, with hNSC and with hNSC immortalized using c-myc wt (c-IhNSC. T-IhNSCs displayed an enhanced self-renewal ability, with their proliferative capacity and clonogenic potential being remarkably comparable to those of v-IhNSC and higher than wild type hNSCs and c-IhNSCs. Upon growth factors removal, T-IhNSC promptly gave rise to well-differentiated neurons, astrocytes and most importantly, to a heretofore undocumented high percentage of human oligodendrocytes (up to 23%. Persistent growth-factor dependence, steady functional properties, lack of ability to generate colonies in soft-agar colony-forming assay and to establish tumors upon orthotopic transplantation, point to the fact that immortalization by c-myc T58A does not bring about tumorigenicity in hNSCs. Hence, this work describes a novel and continuous cell line of immortalized human multipotent neural stem cells, in which the immortalizing agent is represented by a single gene which, in

  16. Somatostatin-Positive Gamma-Aminobutyric Acid Interneuron Deficits in Depression: Cortical Microcircuit and Therapeutic Perspectives.

    Science.gov (United States)

    Fee, Corey; Banasr, Mounira; Sibille, Etienne

    2017-10-15

    The functional integration of external and internal signals forms the basis of information processing and is essential for higher cognitive functions. This occurs in finely tuned cortical microcircuits whose functions are balanced at the cellular level by excitatory glutamatergic pyramidal neurons and inhibitory gamma-aminobutyric acidergic (GABAergic) interneurons. The balance of excitation and inhibition, from cellular processes to neural network activity, is characteristically disrupted in multiple neuropsychiatric disorders, including major depressive disorder (MDD), bipolar disorder, anxiety disorders, and schizophrenia. Specifically, nearly 3 decades of research demonstrate a role for reduced inhibitory GABA level and function across disorders. In MDD, recent evidence from human postmortem and animal studies suggests a selective vulnerability of GABAergic interneurons that coexpress the neuropeptide somatostatin (SST). Advances in cell type-specific molecular genetics have now helped to elucidate several important roles for SST interneurons in cortical processing (regulation of pyramidal cell excitatory input) and behavioral control (mood and cognition). Here, we review evidence for altered inhibitory function arising from GABAergic deficits across disorders and specifically in MDD. We then focus on properties of the cortical microcircuit, where SST-positive GABAergic interneuron deficits may disrupt functioning in several ways. Finally, we discuss the putative origins of SST cell deficits, as informed by recent research, and implications for therapeutic approaches. We conclude that deficits in SST interneurons represent a contributing cellular pathology and therefore a promising target for normalizing altered inhibitory function in MDD and other disorders with reduced SST cell and GABA functions. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  17. The double cortical line: a sign of osteopenia

    International Nuclear Information System (INIS)

    Lamb, C.R.

    1990-01-01

    The double cortical line is a radiographic sign of osteopenia which results from intracortical resorption of bone. This sign is frequently seen in humans with osteopenia but has received minimal attention in the veterinary literature. This report describes the double cortical line in cases of senile osteopenia, nutritional secondary hyperparathyroidism, suspected renal secondary hyperparathyroidism and in the acetabulum following triple pelvic osteotomy for hip dysplasia

  18. The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route

    DEFF Research Database (Denmark)

    Groppa, Sergiu; Schlaak, Boris H; Münchau, Alexander

    2012-01-01

    In non-human primates, invasive tracing and electrostimulation studies have identified strong ipsilateral cortico-cortical connections between dorsal premotor- (PMd) and the primary motor cortex (M1(HAND) ). Here, we applied dual-site transcranial magnetic stimulation (dsTMS) to left PMd and M1......(HAND) through specifically designed minicoils to selectively probe ipsilateral PMd-to-M1(HAND) connectivity in humans. A suprathreshold test stimulus (TS) was applied to M1(HAND) producing a motor evoked potential (MEP) of about 0.5 mV in the relaxed right first dorsal interosseus muscle (FDI......) facilitation did not change as a function of CS intensity. Even at higher intensities, the CS alone failed to elicit a MEP or a cortical silent period in the pre-activated FDI, excluding a direct spread of excitation from PMd to M1(HAND). No MEP facilitation was present while CS was applied rostrally over...

  19. Capacity of Human Dental Follicle Cells to Differentiate into Neural Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Shingo Kanao

    2017-01-01

    Full Text Available The dental follicle is an ectomesenchymal tissue surrounding the developing tooth germ. Human dental follicle cells (hDFCs have the capacity to commit to differentiation into multiple cell types. Here we investigated the capacity of hDFCs to differentiate into neural cells and the efficiency of a two-step strategy involving floating neurosphere-like bodies for neural differentiation. Undifferentiated hDFCs showed a spindle-like morphology and were positive for neural markers such as nestin, β-III-tubulin, and S100β. The cellular morphology of several cells was neuronal-like including branched dendrite-like processes and neurites. Next, hDFCs were used for neurosphere formation in serum-free medium containing basic fibroblast growth factor, epidermal growth factor, and B27 supplement. The number of cells with neuronal-like morphology and that were strongly positive for neural markers increased with sphere formation. Gene expression of neural markers also increased in hDFCs with sphere formation. Next, gene expression of neural markers was examined in hDFCs during neuronal differentiation after sphere formation. Expression of Musashi-1 and Musashi-2, MAP2, GFAP, MBP, and SOX10 was upregulated in hDFCs undergoing neuronal differentiation via neurospheres, whereas expression of nestin and β-III-tubulin was downregulated. In conclusion, hDFCs may be another optimal source of neural/glial cells for cell-based therapies to treat neurological diseases.

  20. Convolutional neural networks for segmentation and object detection of human semen

    DEFF Research Database (Denmark)

    Nissen, Malte Stær; Krause, Oswin; Almstrup, Kristian

    2017-01-01

    We compare a set of convolutional neural network (CNN) architectures for the task of segmenting and detecting human sperm cells in an image taken from a semen sample. In contrast to previous work, samples are not stained or washed to allow for full sperm quality analysis, making analysis harder due...

  1. Observing, performing, and understanding actions: revisiting the role of cortical motor areas in processing of action words

    NARCIS (Netherlands)

    Rüschemeyer, S.A.; Ekman, M.; Ackeren, M.J. van; Kilner, J.

    2014-01-01

    Language content and action/perception have been shown to activate common brain areas in previous neuroimaging studies. However, it is unclear whether overlapping cortical activation reflects a common neural source or adjacent, but distinct, sources. We address this issue by using multivoxel pattern

  2. Post-adolescent developmental changes in cortical complexity

    OpenAIRE

    Sandu, Anca-Larisa; Izard, Edouard; Specht, Karsten; Beneventi, Harald; Lundervold, Arvid; Ystad, Martin

    2014-01-01

    Background: Post-adolescence is known to be a period of general maturation and development in the human brain. In brain imaging, volumetric and morphologic cortical grey-matter changes can easily be assessed, but the analysis of cortical complexity seems to have been broadly neglected for this age interval. Methods: Magnetic resonance imaging (MRI) was used to acquire structural brain images. The study involved 17 adolescents (mean age 14.1 ± 0.27, 11 girls) who were compared with 1...

  3. 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...

  4. The neural basis of the imitation drive.

    Science.gov (United States)

    Hanawa, Sugiko; Sugiura, Motoaki; Nozawa, Takayuki; Kotozaki, Yuka; Yomogida, Yukihito; Ihara, Mizuki; Akimoto, Yoritaka; Thyreau, Benjamin; Izumi, Shinichi; Kawashima, Ryuta

    2016-01-01

    Spontaneous imitation is assumed to underlie the acquisition of important skills by infants, including language and social interaction. In this study, functional magnetic resonance imaging (fMRI) was used to examine the neural basis of 'spontaneously' driven imitation, which has not yet been fully investigated. Healthy participants were presented with movie clips of meaningless bimanual actions and instructed to observe and imitate them during an fMRI scan. The participants were subsequently shown the movie clips again and asked to evaluate the strength of their 'urge to imitate' (Urge) for each action. We searched for cortical areas where the degree of activation positively correlated with Urge scores; significant positive correlations were observed in the right supplementary motor area (SMA) and bilateral midcingulate cortex (MCC) under the imitation condition. These areas were not explained by explicit reasons for imitation or the kinematic characteristics of the actions. Previous studies performed in monkeys and humans have implicated the SMA and MCC/caudal cingulate zone in voluntary actions. This study also confirmed the functional connectivity between Urge and imitation performance using a psychophysiological interaction analysis. Thus, our findings reveal the critical neural components that underlie spontaneous imitation and provide possible reasons why infants imitate spontaneously. © The Author (2015). Published by Oxford University Press.

  5. Computed tomography evaluation of human mandibles with regard to layer thickness and bone density of the cortical bone

    International Nuclear Information System (INIS)

    Markwardt, Jutta; Meissner, H.; Weber, A.; Reitemeier, B.; Laniado, M.

    2013-01-01

    Application of function-restoring individual implants for the bridging of defects in mandibles with continuity separation requires a stable fixation with special use of the cortical bone stumps. Five section planes each of 100 computed tomographies of poly-traumatized patients' jaws were used for measuring the thickness of the cortical layer and the bone density of the mandible. The CT scans of 28 female and 72 male candidates aged between 12 and 86 years with different dentition of the mandible were available. The computed tomographic evaluations of human mandibles regarding the layer thickness of the cortical bone showed that the edge of the mandible in the area of the horizontal branch possesses the biggest layer thickness of the whole of the lower jaws. The highest medians of the cortical bone layer thickness were found in the area of the molars and premolars at the lower edge of the lower jaws in 6-o'clock position, in the area of the molars in the vestibular cranial 10-o'clock position and in the chin region lingual-caudal in the 4-o'clock position. The measurement of the bone density showed the highest values in the 8-o'clock position (vestibular-caudal) in the molar region in both males and females. The average values available of the bone density and the layer thickness of the cortical bone in the various regions of the lower jaw, taking into consideration age, gender and dentition, are an important aid in practice for determining a safe fixation point for implants in the area of the surface layer of the mandible by means of screws or similar fixation elements. (orig.)

  6. Neural Markers of Performance States in an Olympic Athlete: An EEG Case Study in Air-Pistol Shooting

    Directory of Open Access Journals (Sweden)

    Selenia di Fronso, Claudio Robazza, Edson Filho, Laura Bortoli, Silvia Comani, Maurizio Bertollo

    2016-06-01

    Full Text Available This study focused on identifying the neural markers underlying optimal and suboptimal performance experiences of an elite air-pistol shooter, based on the tenets of the multi-action plan (MAP model. According to the MAP model’s assumptions, skilled athletes’ cortical patterns are expected to differ among optimal/automatic (Type 1, optimal/controlled (Type 2, suboptimal/controlled (Type 3, and suboptimal/automatic (Type 4 performance experiences. We collected performance (target pistol shots, cognitive-affective (perceived control, accuracy, and hedonic tone, and cortical activity data (32-channel EEG of an elite shooter. Idiosyncratic descriptive analyses revealed differences in perceived accuracy in regard to optimal and suboptimal performance states. Event-Related Desynchronization/Synchronization analysis supported the notion that optimal-automatic performance experiences (Type 1 were characterized by a global synchronization of cortical arousal associated with the shooting task, whereas suboptimal controlled states (Type 3 were underpinned by high cortical activity levels in the attentional brain network. Results are addressed in light of the neural efficiency hypothesis and reinvestment theory. Perceptual training recommendations aimed at restoring optimal performance levels are discussed.

  7. A 3D human neural cell culture system for modeling Alzheimer’s disease

    Science.gov (United States)

    Kim, Young Hye; Choi, Se Hoon; D’Avanzo, Carla; Hebisch, Matthias; Sliwinski, Christopher; Bylykbashi, Enjana; Washicosky, Kevin J.; Klee, Justin B.; Brüstle, Oliver; Tanzi, Rudolph E.; Kim, Doo Yeon

    2015-01-01

    Stem cell technologies have facilitated the development of human cellular disease models that can be used to study pathogenesis and test therapeutic candidates. These models hold promise for complex neurological diseases such as Alzheimer’s disease (AD) because existing animal models have been unable to fully recapitulate all aspects of pathology. We recently reported the characterization of a novel three-dimensional (3D) culture system that exhibits key events in AD pathogenesis, including extracellular aggregation of β-amyloid and accumulation of hyperphosphorylated tau. Here we provide instructions for the generation and analysis of 3D human neural cell cultures, including the production of genetically modified human neural progenitor cells (hNPCs) with familial AD mutations, the differentiation of the hNPCs in a 3D matrix, and the analysis of AD pathogenesis. The 3D culture generation takes 1–2 days. The aggregation of β-amyloid is observed after 6-weeks of differentiation followed by robust tau pathology after 10–14 weeks. PMID:26068894

  8. Self-Referential Processing, Rumination, and Cortical Midline Structures in Major Depression

    Science.gov (United States)

    Nejad, Ayna Baladi; Fossati, Philippe; Lemogne, Cédric

    2013-01-01

    Major depression is associated with a bias toward negative emotional processing and increased self-focus, i.e., the process by which one engages in self-referential processing. The increased self-focus in depression is suggested to be of a persistent, repetitive and self-critical nature, and is conceptualized as ruminative brooding. The role of the medial prefrontal cortex in self-referential processing has been previously emphasized in acute major depression. There is increasing evidence that self-referential processing as well as the cortical midline structures play a major role in the development, course, and treatment response of major depressive disorder. However, the links between self-referential processing, rumination, and the cortical midline structures in depression are still poorly understood. Here, we reviewed brain imaging studies in depressed patients and healthy subjects that have examined these links. Self-referential processing in major depression seems associated with abnormally increased activity of the anterior cortical midline structures. Abnormal interactions between the lateralized task-positive network, and the midline cortical structures of the default mode network, as well as the emotional response network, may underlie the pervasiveness of ruminative brooding. Furthermore, targeting this maladaptive form of rumination and its underlying neural correlates may be key for effective treatment. PMID:24124416

  9. Self-referential processing, rumination, and cortical midline structures in major depression

    Directory of Open Access Journals (Sweden)

    Ayna Baladi Nejad

    2013-10-01

    Full Text Available Major depression is associated with a bias towards negative emotional processing and increased self-focus, i.e. the process by which one engages in self-referential processing. The increased self-focus in depression is suggested to be of a persistent, repetitive and self-critical nature and is conceptualised as ruminative brooding. The role of the medial prefrontal cortex in self-referential processing has been previously emphasised in acute major depression. There is increasing evidence that self-referential processing as well as the cortical midline structures play a major role in the development, course and treatment response of major depressive disorder. However, the links between self-referential processing, rumination, and the cortical midline structures in depression are still poorly understood. Here, we reviewed brain imaging studies in depressed patients and healthy subjects that have examined these links. The literature suggests that self-referential processing in major depression is associated with increased activity of the anterior cortical midline structures. Abnormal interactions between the lateralised task-positive network, and the midline cortical structures of the default mode network, as well as the emotional response network, may underlie the pervasiveness of ruminative brooding. Furthermore, targeting this maladaptive form of rumination and its underlying neural correlates may be key for effective treatment.

  10. How the human brain goes virtual: distinct cortical regions of the person-processing network are involved in self-identification with virtual agents.

    Science.gov (United States)

    Ganesh, Shanti; van Schie, Hein T; de Lange, Floris P; Thompson, Evan; Wigboldus, Daniël H J

    2012-07-01

    Millions of people worldwide engage in online role-playing with their avatar, a virtual agent that represents the self. Previous behavioral studies have indicated that many gamers identify more strongly with their avatar than with their biological self. Through their avatar, gamers develop social networks and learn new social-cognitive skills. The cognitive neurosciences have yet to identify the neural processes that underlie self-identification with these virtual agents. We applied functional neuroimaging to 22 long-term online gamers and 21 nongaming controls, while they rated personality traits of self, avatar, and familiar others. Strikingly, neuroimaging data revealed greater avatar-referential cortical activity in the left inferior parietal lobe, a region associated with self-identification from a third-person perspective. The magnitude of this brain activity correlated positively with the propensity to incorporate external body enhancements into one's bodily identity. Avatar-referencing furthermore recruited greater activity in the rostral anterior cingulate gyrus, suggesting relatively greater emotional self-involvement with one's avatar. Post-scanning behavioral data revealed superior recognition memory for avatar relative to others. Interestingly, memory for avatar positively covaried with play duration. These findings significantly advance our knowledge about the brain's plasticity to self-identify with virtual agents and the human cognitive-affective potential to live and learn in virtual worlds.

  11. 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.

  12. Cortical Thickness Changes and Their Relationship to Dual-Task Performance following Mild Traumatic Brain Injury in Youth.

    Science.gov (United States)

    Urban, Karolina J; Riggs, Lily; Wells, Greg D; Keightley, Michelle; Chen, Jen-Kai; Ptito, Alain; Fait, Philippe; Taha, Tim; Sinopoli, Katia J

    2017-02-15

    Mild traumatic brain injury (mTBI) is common in youth, especially in those who participate in sport. Recent investigations from our group have shown that asymptomatic children and adolescents with mTBI continue to exhibit alterations in neural activity and cognitive performance compared with those without a history of mTBI. This is an intriguing finding, given that current return-to-learn and return-to-play protocols rely predominately on subjective symptom reports, which may not be sensitive enough to detect subtle injury-related changes. As a result, youth may be at greater risk for re-injury and long-term consequences if they are cleared for activity while their brains continue to be compromised. It is currently unknown whether mTBI also affects brain microstructure in the developing brain, particularly cortical thickness, and whether such changes are also related to cognitive performance. The present study examined cortical thickness in 13 asymptomatic youth (10-14 years old) who had sustained an mTBI 3-8 months prior to testing compared with 14 age-matched typically developing controls. Cortical thickness was also examined in relation to working memory performance during single and dual task paradigms. The results show that youth who had sustained an mTBI had thinner cortices in the left dorsolateral prefrontal region and right anterior and posterior inferior parietal lobes. Additionally, cortical thinning was associated with slower reaction time during the dual-task condition in the injured youth only. The results also point to a possible relationship between functional and structural alterations as a result of mTBI in youth, and lend evidence for neural changes beyond symptom resolution.

  13. APC/C-Cdh1 coordinates neurogenesis and cortical size during development

    Science.gov (United States)

    Delgado-Esteban, Maria; García-Higuera, Irene; Maestre, Carolina; Moreno, Sergio; Almeida, Angeles

    2013-12-01

    The morphology of the adult brain is the result of a delicate balance between neural progenitor proliferation and the initiation of neurogenesis in the embryonic period. Here we assessed whether the anaphase-promoting complex/cyclosome (APC/C) cofactor, Cdh1—which regulates mitosis exit and G1-phase length in dividing cells—regulates neurogenesis in vivo. We use an embryo-restricted Cdh1 knockout mouse model and show that functional APC/C-Cdh1 ubiquitin ligase activity is required for both terminal differentiation of cortical neurons in vitro and neurogenesis in vivo. Further, genetic ablation of Cdh1 impairs the ability of APC/C to promote neurogenesis by delaying the exit of the progenitor cells from the cell cycle. This causes replicative stress and p53-mediated apoptotic death resulting in decreased number of cortical neurons and cortex size. These results demonstrate that APC/C-Cdh1 coordinates cortical neurogenesis and size, thus posing Cdh1 in the molecular pathogenesis of congenital neurodevelopmental disorders, such as microcephaly.

  14. Canonical Cortical Circuit Model Explains Rivalry, Intermittent Rivalry, and Rivalry Memory.

    Directory of Open Access Journals (Sweden)

    Shashaank Vattikuti

    2016-05-01

    Full Text Available It has been shown that the same canonical cortical circuit model with mutual inhibition and a fatigue process can explain perceptual rivalry and other neurophysiological responses to a range of static stimuli. However, it has been proposed that this model cannot explain responses to dynamic inputs such as found in intermittent rivalry and rivalry memory, where maintenance of a percept when the stimulus is absent is required. This challenges the universality of the basic canonical cortical circuit. Here, we show that by including an overlooked realistic small nonspecific background neural activity, the same basic model can reproduce intermittent rivalry and rivalry memory without compromising static rivalry and other cortical phenomena. The background activity induces a mutual-inhibition mechanism for short-term memory, which is robust to noise and where fine-tuning of recurrent excitation or inclusion of sub-threshold currents or synaptic facilitation is unnecessary. We prove existence conditions for the mechanism and show that it can explain experimental results from the quartet apparent motion illusion, which is a prototypical intermittent rivalry stimulus.

  15. Natural lecithin promotes neural network complexity and activity

    Science.gov (United States)

    Latifi, Shahrzad; Tamayol, Ali; Habibey, Rouhollah; Sabzevari, Reza; Kahn, Cyril; Geny, David; Eftekharpour, Eftekhar; Annabi, Nasim; Blau, Axel; Linder, Michel; Arab-Tehrany, Elmira

    2016-01-01

    Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called “essential” fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications. PMID:27228907

  16. Natural lecithin promotes neural network complexity and activity.

    Science.gov (United States)

    Latifi, Shahrzad; Tamayol, Ali; Habibey, Rouhollah; Sabzevari, Reza; Kahn, Cyril; Geny, David; Eftekharpour, Eftekhar; Annabi, Nasim; Blau, Axel; Linder, Michel; Arab-Tehrany, Elmira

    2016-05-27

    Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called "essential" fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications.

  17. Human seizures couple across spatial scales through travelling wave dynamics

    Science.gov (United States)

    Martinet, L.-E.; Fiddyment, G.; Madsen, J. R.; Eskandar, E. N.; Truccolo, W.; Eden, U. T.; Cash, S. S.; Kramer, M. A.

    2017-04-01

    Epilepsy--the propensity toward recurrent, unprovoked seizures--is a devastating disease affecting 65 million people worldwide. Understanding and treating this disease remains a challenge, as seizures manifest through mechanisms and features that span spatial and temporal scales. Here we address this challenge through the analysis and modelling of human brain voltage activity recorded simultaneously across microscopic and macroscopic spatial scales. We show that during seizure large-scale neural populations spanning centimetres of cortex coordinate with small neural groups spanning cortical columns, and provide evidence that rapidly propagating waves of activity underlie this increased inter-scale coupling. We develop a corresponding computational model to propose specific mechanisms--namely, the effects of an increased extracellular potassium concentration diffusing in space--that support the observed spatiotemporal dynamics. Understanding the multi-scale, spatiotemporal dynamics of human seizures--and connecting these dynamics to specific biological mechanisms--promises new insights to treat this devastating disease.

  18. Neural Synchrony during Response Production and Inhibition

    Science.gov (United States)

    Müller, Viktor; Anokhin, Andrey P.

    2012-01-01

    Inhibition of irrelevant information (conflict monitoring) and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs) elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG) recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300–600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations. PMID:22745691

  19. Neural synchrony during response production and inhibition.

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    Viktor Müller

    Full Text Available Inhibition of irrelevant information (conflict monitoring and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300-600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations.

  20. Patterns of differences in brain morphology in humans as compared to extant apes.

    Science.gov (United States)

    Aldridge, Kristina

    2011-01-01

    Although human evolution is characterized by a vast increase in brain size, it is not clear whether or not certain regions of the brain are enlarged disproportionately in humans, or how this enlargement relates to differences in overall neural morphology. The aim of this study is to determine whether or not there are specific suites of features that distinguish the morphology of the human brain from that of apes. The study sample consists of whole brain, in vivo magnetic resonance images (MRIs) of anatomically modern humans (Homo sapiens sapiens) and five ape species (gibbons, orangutans, gorillas, chimpanzees, bonobos). Twenty-nine 3D landmarks, including surface and internal features of the brain were located on 3D MRI reconstructions of each individual using MEASURE software. Landmark coordinate data were scaled for differences in size and analyzed using Euclidean Distance Matrix Analysis (EDMA) to statistically compare the brains of each non-human ape species to the human sample. Results of analyses show both a pattern of brain morphology that is consistently different between all apes and humans, as well as patterns that differ among species. Further, both the consistent and species-specific patterns include cortical and subcortical features. The pattern that remains consistent across species indicates a morphological reorganization of 1) relationships between cortical and subcortical frontal structures, 2) expansion of the temporal lobe and location of the amygdala, and 3) expansion of the anterior parietal region. Additionally, results demonstrate that, although there is a pattern of morphology that uniquely defines the human brain, there are also patterns that uniquely differentiate human morphology from the morphology of each non-human ape species, indicating that reorganization of neural morphology occurred at the evolutionary divergence of each of these groups. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate

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    Priya Srikanth

    2015-09-01

    Full Text Available Genetic and clinical association studies have identified disrupted in schizophrenia 1 (DISC1 as a candidate risk gene for major mental illness. DISC1 is interrupted by a balanced chr(1;11 translocation in a Scottish family in which the translocation predisposes to psychiatric disorders. We investigate the consequences of DISC1 interruption in human neural cells using TALENs or CRISPR-Cas9 to target the DISC1 locus. We show that disruption of DISC1 near the site of the translocation results in decreased DISC1 protein levels because of nonsense-mediated decay of long splice variants. This results in an increased level of canonical Wnt signaling in neural progenitor cells and altered expression of fate markers such as Foxg1 and Tbr2. These gene expression changes are rescued by antagonizing Wnt signaling in a critical developmental window, supporting the hypothesis that DISC1-dependent suppression of basal Wnt signaling influences the distribution of cell types generated during cortical development.

  2. Canonical cortical circuits: current evidence and theoretical implications

    Directory of Open Access Journals (Sweden)

    Capone F

    2016-04-01

    contexts. The fourth section (Extending the concept of canonical circuit to economic decisions circuits reviews the experiments conducted in humans by using transcranial magnetic stimulation to demonstrate the validity of the canonical cortical circuit model. The fifth section (Extending the concept of canonical circuit to economic decisions circuits explores the hypothesis that also complex human behaviors such as economic decision-making could also be explained in terms of canonical cortical circuit. The final section (Conclusion provides a critical point of view, evidencing the limits of the available data and tracking directions for future research.Keywords: canonical cortical circuit, cortex, cortical layers, cortical physiology

  3. Reduced cortical thickness in veterans exposed to early life trauma.

    Science.gov (United States)

    Corbo, Vincent; Salat, David H; Amick, Melissa M; Leritz, Elizabeth C; Milberg, William P; McGlinchey, Regina E

    2014-08-30

    Studies have shown that early life trauma may influence neural development and increase the risk of developing psychological disorders in adulthood. We used magnetic resonance imaging to examine the impact of early life trauma on the relationship between current posttraumatic stress disorder (PTSD) symptoms and cortical thickness/subcortical volumes in a sample of deployed personnel from Operation Enduring Freedom/Operation Iraqi Freedom. A group of 108 service members enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) were divided into those with interpersonal early life trauma (EL-Trauma+) and Control (without interpersonal early life trauma) groups based on the Traumatic Life Events Questionnaire. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale. Cortical thickness and subcortical volumes were analyzed using the FreeSurfer image analysis package. Thickness of the paracentral and posterior cingulate regions was positively associated with PTSD severity in the EL-Trauma+ group and negatively in the Control group. In the EL-Trauma+ group, both the right amygdala and the left hippocampus were positively associated with PTSD severity. This study illustrates a possible influence of early life trauma on the vulnerability of specific brain regions to stress. Changes in neural morphometry may provide information about the emergence and maintenance of symptoms in individuals with PTSD. Published by Elsevier Ireland Ltd.

  4. The Causal Inference of Cortical Neural Networks during Music Improvisations

    Science.gov (United States)

    Wan, Xiaogeng; Crüts, Björn; Jensen, Henrik Jeldtoft

    2014-01-01

    We present an EEG study of two music improvisation experiments. Professional musicians with high level of improvisation skills were asked to perform music either according to notes (composed music) or in improvisation. Each piece of music was performed in two different modes: strict mode and “let-go” mode. Synchronized EEG data was measured from both musicians and listeners. We used one of the most reliable causality measures: conditional Mutual Information from Mixed Embedding (MIME), to analyze directed correlations between different EEG channels, which was combined with network theory to construct both intra-brain and cross-brain networks. Differences were identified in intra-brain neural networks between composed music and improvisation and between strict mode and “let-go” mode. Particular brain regions such as frontal, parietal and temporal regions were found to play a key role in differentiating the brain activities between different playing conditions. By comparing the level of degree centralities in intra-brain neural networks, we found a difference between the response of musicians and the listeners when comparing the different playing conditions. PMID:25489852

  5. The causal inference of cortical neural networks during music improvisations.

    Science.gov (United States)

    Wan, Xiaogeng; Crüts, Björn; Jensen, Henrik Jeldtoft

    2014-01-01

    We present an EEG study of two music improvisation experiments. Professional musicians with high level of improvisation skills were asked to perform music either according to notes (composed music) or in improvisation. Each piece of music was performed in two different modes: strict mode and "let-go" mode. Synchronized EEG data was measured from both musicians and listeners. We used one of the most reliable causality measures: conditional Mutual Information from Mixed Embedding (MIME), to analyze directed correlations between different EEG channels, which was combined with network theory to construct both intra-brain and cross-brain networks. Differences were identified in intra-brain neural networks between composed music and improvisation and between strict mode and "let-go" mode. Particular brain regions such as frontal, parietal and temporal regions were found to play a key role in differentiating the brain activities between different playing conditions. By comparing the level of degree centralities in intra-brain neural networks, we found a difference between the response of musicians and the listeners when comparing the different playing conditions.

  6. The causal inference of cortical neural networks during music improvisations.

    Directory of Open Access Journals (Sweden)

    Xiaogeng Wan

    Full Text Available We present an EEG study of two music improvisation experiments. Professional musicians with high level of improvisation skills were asked to perform music either according to notes (composed music or in improvisation. Each piece of music was performed in two different modes: strict mode and "let-go" mode. Synchronized EEG data was measured from both musicians and listeners. We used one of the most reliable causality measures: conditional Mutual Information from Mixed Embedding (MIME, to analyze directed correlations between different EEG channels, which was combined with network theory to construct both intra-brain and cross-brain networks. Differences were identified in intra-brain neural networks between composed music and improvisation and between strict mode and "let-go" mode. Particular brain regions such as frontal, parietal and temporal regions were found to play a key role in differentiating the brain activities between different playing conditions. By comparing the level of degree centralities in intra-brain neural networks, we found a difference between the response of musicians and the listeners when comparing the different playing conditions.

  7. Brief Report: Robo1 Regulates the Migration of Human Subventricular Zone Neural Progenitor Cells During Development.

    Science.gov (United States)

    Guerrero-Cazares, Hugo; Lavell, Emily; Chen, Linda; Schiapparelli, Paula; Lara-Velazquez, Montserrat; Capilla-Gonzalez, Vivian; Clements, Anna Christina; Drummond, Gabrielle; Noiman, Liron; Thaler, Katrina; Burke, Anne; Quiñones-Hinojosa, Alfredo

    2017-07-01

    Human neural progenitor cell (NPC) migration within the subventricular zone (SVZ) of the lateral ganglionic eminence is an active process throughout early brain development. The migration of human NPCs from the SVZ to the olfactory bulb during fetal stages resembles what occurs in adult rodents. As the human brain develops during infancy, this migratory stream is drastically reduced in cell number and becomes barely evident in adults. The mechanisms regulating human NPC migration are unknown. The Slit-Robo signaling pathway has been defined as a chemorepulsive cue involved in axon guidance and neuroblast migration in rodents. Slit and Robo proteins expressed in the rodent brain help guide neuroblast migration from the SVZ through the rostral migratory stream to the olfactory bulb. Here, we present the first study on the role that Slit and Robo proteins play in human-derived fetal neural progenitor cell migration (hfNPC). We describe that Robo1 and Robo2 isoforms are expressed in the human fetal SVZ. Furthermore, we demonstrate that Slit2 is able to induce a chemorepellent effect on the migration of hfNPCs derived from the human fetal SVZ. In addition, when Robo1 expression is inhibited, hfNPCs are unable to migrate to the olfactory bulb of mice when injected in the anterior SVZ. Our findings indicate that the migration of human NPCs from the SVZ is partially regulated by the Slit-Robo axis. This pathway could be regulated to direct the migration of NPCs in human endogenous neural cell therapy. Stem Cells 2017;35:1860-1865. © 2017 AlphaMed Press.

  8. The effect of binaural beats on verbal working memory and cortical connectivity

    Science.gov (United States)

    Beauchene, Christine; Abaid, Nicole; Moran, Rosalyn; Diana, Rachel A.; Leonessa, Alexander

    2017-04-01

    Objective. Synchronization in activated regions of cortical networks affect the brain’s frequency response, which has been associated with a wide range of states and abilities, including memory. A non-invasive method for manipulating cortical synchronization is binaural beats. Binaural beats take advantage of the brain’s response to two pure tones, delivered independently to each ear, when those tones have a small frequency mismatch. The mismatch between the tones is interpreted as a beat frequency, which may act to synchronize cortical oscillations. Neural synchrony is particularly important for working memory processes, the system controlling online organization and retention of information for successful goal-directed behavior. Therefore, manipulation of synchrony via binaural beats provides a unique window into working memory and associated connectivity of cortical networks. Approach. In this study, we examined the effects of different acoustic stimulation conditions during an N-back working memory task, and we measured participant response accuracy and cortical network topology via EEG recordings. Six acoustic stimulation conditions were used: None, Pure Tone, Classical Music, 5 Hz binaural beats, 10 Hz binaural beats, and 15 Hz binaural beats. Main results. We determined that listening to 15 Hz binaural beats during an N-Back working memory task increased the individual participant’s accuracy, modulated the cortical frequency response, and changed the cortical network connection strengths during the task. Only the 15 Hz binaural beats produced significant change in relative accuracy compared to the None condition. Significance. Listening to 15 Hz binaural beats during the N-back task activated salient frequency bands and produced networks characterized by higher information transfer as compared to other auditory stimulation conditions.

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

    Science.gov (United States)

    Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

    2013-02-20

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

  10. Human preferences for symmetry: subjective experience, cognitive conflict and cortical brain activity.

    Directory of Open Access Journals (Sweden)

    David W Evans

    Full Text Available This study examines the links between human perceptions, cognitive biases and neural processing of symmetrical stimuli. While preferences for symmetry have largely been examined in the context of disorders such as obsessive-compulsive disorder and autism spectrum disorders, we examine various these phenomena in non-clinical subjects and suggest that such preferences are distributed throughout the typical population as part of our cognitive and neural architecture. In Experiment 1, 82 young adults reported on the frequency of their obsessive-compulsive spectrum behaviors. Subjects also performed an emotional Stroop or variant of an Implicit Association Task (the OC-CIT developed to assess cognitive biases for symmetry. Data not only reveal that subjects evidence a cognitive conflict when asked to match images of positive affect with asymmetrical stimuli, and disgust with symmetry, but also that their slowed reaction times when asked to do so were predicted by reports of OC behavior, particularly checking behavior. In Experiment 2, 26 participants were administered an oddball Event-Related Potential task specifically designed to assess sensitivity to symmetry as well as the OC-CIT. These data revealed that reaction times on the OC-CIT were strongly predicted by frontal electrode sites indicating faster processing of an asymmetrical stimulus (unparallel lines relative to a symmetrical stimulus (parallel lines. The results point to an overall cognitive bias linking disgust with asymmetry and suggest that such cognitive biases are reflected in neural responses to symmetrical/asymmetrical stimuli.

  11. Selective attention on representations in working memory: cognitive and neural mechanisms.

    Science.gov (United States)

    Ku, Yixuan

    2018-01-01

    Selective attention and working memory are inter-dependent core cognitive functions. It is critical to allocate attention on selected targets during the capacity-limited working memory processes to fulfill the goal-directed behavior. The trends of research on both topics are increasing exponentially in recent years, and it is considered that selective attention and working memory share similar underlying neural mechanisms. Different types of attention orientation in working memory are introduced by distinctive cues, and the means using retrospective cues are strengthened currently as it is manipulating the representation in memory, instead of the perceptual representation. The cognitive and neural mechanisms of the retro-cue effects are further reviewed, as well as the potential molecular mechanism. The frontal-parietal network that is involved in both attention and working memory is also the neural candidate for attention orientation during working memory. Neural oscillations in the gamma and alpha/beta oscillations may respectively be employed for the feedforward and feedback information transfer between the sensory cortices and the association cortices. Dopamine and serotonin systems might interact with each other subserving the communication between memory and attention. In conclusion, representations which attention shifts towards are strengthened, while representations which attention moves away from are degraded. Studies on attention orientation during working memory indicates the flexibility of the processes of working memory, and the beneficial way that overcome the limited capacity of working memory.

  12. Somatosensory cortices are required for the acquisition of morphine-induced conditioned place preference.

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    Zhiqiang Meng

    Full Text Available BACKGROUND: Sensory system information is thought to play an important role in drug addiction related responses. However, how somatic sensory information participates in the drug related behaviors is still unclear. Many studies demonstrated that drug addiction represents a pathological usurpation of neural mechanisms of learning and memory that normally relate to the pursuit of rewards. Thus, elucidate the role of somatic sensory in drug related learning and memory is of particular importance to understand the neurobiological mechanisms of drug addiction. PRINCIPAL FINDINGS: In the present study, we investigated the role of somatosensory system in reward-related associative learning using the conditioned place preference model. Lesions were made in somatosensory cortices either before or after conditioning training. We found that lesion of somatosensory cortices before, rather than after morphine conditioning impaired the acquisition of place preference. CONCLUSION: These results demonstrate that somatosensory cortices are necessary for the acquisition but not retention of morphine induced place preference.

  13. Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

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    Montzka Katrin

    2009-03-01

    Full Text Available Abstract Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as

  14. Focal Transplantation of Human iPSC-Derived Glial-Rich Neural Progenitors Improves Lifespan of ALS Mice

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    Takayuki Kondo

    2014-08-01

    Full Text Available Transplantation of glial-rich neural progenitors has been demonstrated to attenuate motor neuron degeneration and disease progression in rodent models of mutant superoxide dismutase 1 (SOD1-mediated amyotrophic lateral sclerosis (ALS. However, translation of these results into a clinical setting requires a renewable human cell source. Here, we derived glial-rich neural progenitors from human iPSCs and transplanted them into the lumbar spinal cord of ALS mouse models. The transplanted cells differentiated into astrocytes, and the treated mouse group showed prolonged lifespan. Our data suggest a potential therapeutic mechanism via activation of AKT signal. The results demonstrated the efficacy of cell therapy for ALS by the use of human iPSCs as cell source.

  15. Signs of noise-induced neural degeneration in humans

    DEFF Research Database (Denmark)

    Holtegaard, Pernille; Olsen, Steen Østergaard

    2015-01-01

    of background noise, while leaving the processing of low-level stimuli unaffected. The purpose of this study was to investigate if signs of such primary neural damage from noise-exposure could also be found in noiseexposed human individuals. It was investigated: (1) if noise-exposed listeners with hearing......Animal studies demonstrated that noise exposure causes a primary and selective loss of auditory-nerve fibres with low spontaneous firing rate. This neuronal impairment, if also present in humans, can be assumed to affect the processing of supra-threshold stimuli, especially in the presence...... thresholds within the “normal” range perform poorer, in terms of their speech recognition threshold in noise (SRTN), and (2) if auditory brainstem responses (ABR) reveal lower amplitude of wave I in the noise-exposed listeners. A test group of noise/music-exposed individuals and a control group were...

  16. Grey matter volume and cortical structure in Prader-Willi syndrome compared to typically developing young adults

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    Katherine E. Manning

    2018-01-01

    Full Text Available Prader-Willi syndrome (PWS is a neurodevelopmental disorder of genomic imprinting, presenting with a characteristic overeating disorder, mild to moderate intellectual disability, and a variable range of social and behavioral difficulties. Consequently, widespread alterations in neural structure and developmental and maturational trajectory would be expected. To date, there have been few quantitative and systematic studies of brain morphology in PWS, although alterations of volume and of cortical organisation have been reported. This study aimed to investigate, in detail, the structure of grey matter and cortex in the brain in a sample of young adults with PWS in a well-matched case-controlled analysis. 20 young adults with PWS, aged 19–27 years, underwent multiparameter mapping magnetic resonance imaging sequences, from which measures of grey matter volume, cortical thickness and magnetisation transfer saturation, as a proxy measure of myelination, were examined. These variables were investigated in comparison to a control group of 40 typically developing young adults, matched for age and sex. A voxel-based morphometry analysis identified large and widespread bilateral clusters of both increased and decreased grey matter volume in the brain in PWS. In particular, widespread areas of increased volume encompassed parts of the prefrontal cortex, especially medially, the majority of the cingulate cortices, from anterior to posterior aspects, insula cortices, and areas of the parietal and temporal cortices. Increased volume was also reported in the caudate, putamen and thalamus. The most ventromedial prefrontal areas, in contrast, showed reduced volume, as did the parts of the medial temporal lobe, bilateral temporal poles, and a small cluster in the right lateral prefrontal cortex. Analysis of cortical structure revealed that areas of increased volume in the PWS group were largely driven by greater cortical thickness. Conversely, analysis of

  17. Grey matter volume and cortical structure in Prader-Willi syndrome compared to typically developing young adults.

    Science.gov (United States)

    Manning, Katherine E; Tait, Roger; Suckling, John; Holland, Anthony J

    2018-01-01

    Prader-Willi syndrome (PWS) is a neurodevelopmental disorder of genomic imprinting, presenting with a characteristic overeating disorder, mild to moderate intellectual disability, and a variable range of social and behavioral difficulties. Consequently, widespread alterations in neural structure and developmental and maturational trajectory would be expected. To date, there have been few quantitative and systematic studies of brain morphology in PWS, although alterations of volume and of cortical organisation have been reported. This study aimed to investigate, in detail, the structure of grey matter and cortex in the brain in a sample of young adults with PWS in a well-matched case-controlled analysis. 20 young adults with PWS, aged 19-27 years, underwent multiparameter mapping magnetic resonance imaging sequences, from which measures of grey matter volume, cortical thickness and magnetisation transfer saturation, as a proxy measure of myelination, were examined. These variables were investigated in comparison to a control group of 40 typically developing young adults, matched for age and sex. A voxel-based morphometry analysis identified large and widespread bilateral clusters of both increased and decreased grey matter volume in the brain in PWS. In particular, widespread areas of increased volume encompassed parts of the prefrontal cortex, especially medially, the majority of the cingulate cortices, from anterior to posterior aspects, insula cortices, and areas of the parietal and temporal cortices. Increased volume was also reported in the caudate, putamen and thalamus. The most ventromedial prefrontal areas, in contrast, showed reduced volume, as did the parts of the medial temporal lobe, bilateral temporal poles, and a small cluster in the right lateral prefrontal cortex. Analysis of cortical structure revealed that areas of increased volume in the PWS group were largely driven by greater cortical thickness. Conversely, analysis of myelin content using

  18. Thalamo-cortical activation and connectivity during response preparation in adults with persistent and remitted ADHD.

    Science.gov (United States)

    Clerkin, Suzanne M; Schulz, Kurt P; Berwid, Olga G; Fan, Jin; Newcorn, Jeffrey H; Tang, Cheuk Y; Halperin, Jeffrey M

    2013-09-01

    The neural correlates of stimulus-driven processes, such as response preparation, have been posited to be associated with the onset of attention deficit hyperactivity disorder (ADHD) while being distinct from the neural mechanisms associated with recovery. The authors tested this hypothesis in adults with remitted and persistent ADHD. Thirty-eight young adults who were diagnosed with combined-type ADHD in childhood (probands) and 32 carefully matched comparison subjects were followed longitudinally and scanned with functional MRI while performing an event-related cued reaction time task. Probands were characterized as individuals with persistent or remitted ADHD. Differences in thalamo-cortical activation and functional connectivity during response preparation between comparison subjects and probands and between individuals with persistent ADHD and those with remitted ADHD were assessed by contrasting neural activation and functional connectivity during cue or noncue events. Probands exhibited less cue-related activation than comparison subjects in the thalamus, anterior cingulate cortex, supplementary motor area, inferior parietal lobe, and dorsolateral prefrontal cortex despite similar overall patterns of activation. There were no differences in activation between individuals in the remitted ADHD group and those in the persistent ADHD group in any hypothesized regions. However, cue-related functional connectivity between the right thalamus and brainstem was greater in comparison subjects relative to probands, and cue-related connectivity was greater between the right thalamus and prefrontal regions in individuals with remitted ADHD relative to those with persistent ADHD. Decreased thalamo-cortical activation during response preparation was present in adults diagnosed with ADHD in childhood regardless of symptom remission in adulthood, and may be partly driven by less functional coordination between the brainstem and thalamus. Greater functional integration of the

  19. Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Liang [East Hospital, Tongji University School of Medicine, Shanghai (China); Dong, Chuanming [East Hospital, Tongji University School of Medicine, Shanghai (China); Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong (China); Sun, Chenxi; Ma, Rongjie; Yang, Danjing [East Hospital, Tongji University School of Medicine, Shanghai (China); Zhu, Hongwen, E-mail: hongwen_zhu@hotmail.com [Tianjin Hospital, Tianjin Academy of Integrative Medicine, Tianjin (China); Xu, Jun, E-mail: xunymc2000@yahoo.com [East Hospital, Tongji University School of Medicine, Shanghai (China)

    2015-08-21

    Aging of neural stem cell, which can affect brain homeostasis, may be caused by many cellular mechanisms. Autophagy dysfunction was found in aged and neurodegenerative brains. However, little is known about the relationship between autophagy and human neural stem cell (hNSC) aging. The present study used 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to treat neural precursor cells (NPCs) derived from human embryonic stem cell (hESC) line H9 and investigate related molecular mechanisms involved in this process. MPTP-treated NPCs were found to undergo premature senescence [determined by increased senescence-associated-β-galactosidase (SA-β-gal) activity, elevated intracellular reactive oxygen species level, and decreased proliferation] and were associated with impaired autophagy. Additionally, the cellular senescence phenotypes were manifested at the molecular level by a significant increase in p21 and p53 expression, a decrease in SOD2 expression, and a decrease in expression of some key autophagy-related genes such as Atg5, Atg7, Atg12, and Beclin 1. Furthermore, we found that the senescence-like phenotype of MPTP-treated hNPCs was rejuvenated through treatment with a well-known autophagy enhancer rapamycin, which was blocked by suppression of essential autophagy gene Beclin 1. Taken together, these findings reveal the critical role of autophagy in the process of hNSC aging, and this process can be reversed by activating autophagy. - Highlights: • We successfully establish hESC-derived neural precursor cells. • MPTP treatment induced senescence-like state in hESC-derived NPCs. • MPTP treatment induced impaired autophagy of hESC-derived NPCs. • MPTP-induced hESC-derived NPC senescence was rejuvenated by activating autophagy.

  20. Multispectral embedding-based deep neural network for three-dimensional human pose recovery

    Science.gov (United States)

    Yu, Jialin; Sun, Jifeng

    2018-01-01

    Monocular image-based three-dimensional (3-D) human pose recovery aims to retrieve 3-D poses using the corresponding two-dimensional image features. Therefore, the pose recovery performance highly depends on the image representations. We propose a multispectral embedding-based deep neural network (MSEDNN) to automatically obtain the most discriminative features from multiple deep convolutional neural networks and then embed their penultimate fully connected layers into a low-dimensional manifold. This compact manifold can explore not only the optimum output from multiple deep networks but also the complementary properties of them. Furthermore, the distribution of each hierarchy discriminative manifold is sufficiently smooth so that the training process of our MSEDNN can be effectively implemented only using few labeled data. Our proposed network contains a body joint detector and a human pose regressor that are jointly trained. Extensive experiments conducted on four databases show that our proposed MSEDNN can achieve the best recovery performance compared with the state-of-the-art methods.